2019 Annual Meeting AANextra Tuesday

THE ANNUAL MEETING NEWS DAILY

Tuesday, May 7, 2019

IMPORTANT CLINICAL TRIALS SHOWCASED IN TODAY’S PLENARY Make your way to the Terrace Ballroom this morning for the Clinical Trials Plenary Session from 9:15 a.m. to 11:30 a.m. The session will showcase eight experts presenting the latest updates within several clinical trials that affect patient care, conducted over the course of the last year and identified from other society meetings.

Moderators Holly E. Hinson, MD, MCR, FAAN Oregon Health & Science University, Portland, OR Member, AAN Science Committee Deborah Hall, MD, PhD, FAAN Rush University, Chicago, IL Member, AAN Science Committee

Hinson

Hall

Continued on page 30 u

Movement Disorders Featured in Today’s Invited Science Session Hot topics in Parkinson’s disease will be featured in today’s Invited Science Session from 3:30 p.m. to 5:30 p.m. in Room 113 AB. The session, in collaboration with the International Parkinson and Movement Disorder Society, will focus on innovative, cutting-edge progress in the basic, translational, and clinical sciences related to genetics, pathophysiology, and therapeutic approaches that are driving the field forward toward a more complete understanding of Parkinson’s disease.

These abstracts were the top-ranking presentations at the Movement Disorder International Congress in Hong Kong in 2018.

Continued on page 28 u

Inside

7 Emerging Science Abstracts to Be Presented Today Twelve abstracts will be presented today in plenary and poster sessions, along with a data blitz presentation, as part of the Emerging Science program.

Abstracts qualify for Emerging Science presentations by having key aspects of research conducted after the October 22 abstract submission deadline and must be new and of sufficient scientific importance to warrant expedited presentation and publication.

Continued on page 34 u

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New AAN Tourette Guideline Shared in Press Conference with World Media External Validation of Axon Registry Data Demonstrates Value

Science as a 10 Leveraging Tool for Social Change Is National Institutes 19 Today of Health Day

In Multiple

Sclerosis—

GREY MATTERS, TOO

FIND OUT WHY

Booth 2300

© 2019 Celgene Corporation All rights reserved.

03/19 US-CLG-19-0291

Tuesday, May 7 Cover Important Clinical Trials Showcased in Today’s Plenary

Movement Disorders Featured in Today’s Invited Science Session

Emerging Science Abstracts to Be Presented Today

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Daily Reminders

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New AAN Tourette Guideline Shared in Press Conference with World Media

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Join Neurology Today® at the Annual Meeting

8

External Validation of Axon Registry Data Demonstrates Value

Today’s Experiential Learning Area Highlights

10 Leveraging Science as a Tool for Social Change

12 What Excited You Today at #AANAM? 13 Boxed Lunch Menu 14 What Are Your Colleagues Saying?

19 Today Is National Institutes of Health Day in the Research Corner Experiential Learning Area

19 Enhance Your Annual Meeting

Experience with Digital Library

20 Board Member Gains Valuable Insight, Satisfaction Through Leadership Program

27 The Best of Philly from Those Who Know It Best

28 Find the Latest Research at Today’s Poster Session

28 Is Your Alumni Group Getting Together?

We are experiencing an issue where some slides/syllabi files for courses are not accessible through the mobile app or the online site. This has been isolated to a routing issue due to a growing internet outage in New Jersey. We apologize for the inconvenience. Please note that all slides/syllabi will be available after the Annual Meeting and will be available for one year after the end of the meeting.

The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction.

Contact Information: 201 Chicago Avenue Minneapolis, MN 55415 USA Phone: (800) 879-1960 (Toll Free) or

(612) 928-6100 (International) Fax: (612) 454-2744 Email: memberservices@aan.com Website: AAN.com AAN Chief Executive Officer:

Catherine M. Rydell, CAE Managing Editor: Angela M. Babb, CAE, APR Editor: Tim Streeter Writers: Ryan Knoke, Sarah Parsons Designers: Siu Lee, Andrew Imholte Photography: Will Evans Printing: Phoenix Lithographing Corporation Email: aannews@aan.com AANextra is published by the American Academy of Neurology.

Daily Reminders Education Program Syllabi and Slides

The Vision of the AAN is to be indispensable to our members.

May 20 Is Deadline to Submit Online Evaluations for Annual Meeting CME

The American Academy of Neurology’s registered trademarks and service marks are registered in the United States and various other countries around the world. “American Brain Foundation” is a registered service mark of the American Brain Foundation and is registered in the United States.

Complete your evaluations to get your CME hours by using the AAN Conferences Mobile App at AAN.com/view/MobileApp or by visiting AAN.com/view/CME. CME requests may be made until Monday, May 20, 2019.

Transcripts will be emailed approximately six weeks after the meeting. AAN members can also access their transcript via NeuroTracker™ at AAN.com/view/ NeuroTracker. The American Academy of Neurology sincerely thanks Phoenix Lithographing Corporation for its outstanding service, steadfast professionalism, and high quality standards, as well as its generous donation of the 2019 Brain Health Fair program guide.

Today’s Experiential Learning Area Highlights HeadTalks

Research Corner

Live Intraoperative Monitoring 3:00 p.m.–3:45 p.m.

Be sure to attend tomorrow’s session:

This highly interactive event will demonstrate how real-time intraoperative monitoring is performed using real-time case(s) to offer a look at how Moschonas remote intraoperative monitoring takes place and is part of the expanding telemedicine field. Constantine Moschonas, MD, FAAN, will also take the audience through abnormal intraoperative monitoring cases for an expanded learning experience.

How to Write and Publish Research Papers, Reviews, and Other Scientific Communications Wednesday, 7:00 a.m.–7:30 a.m.

In tomorrow’s session, Mark Hallett, MD, FAAN, Hallett will review how to best prepare a manuscript, choose the right format, select the most appropriate journal, and get the manuscript accepted for publication. Issues such as impact factor and predatory journals will be discussed.

Live Well: Taking Care of Your Patients Starts with Taking Care of You

Navigating Your Career

Free Chair Massages 12:00 p.m.–4:00 p.m.

How to Create a Department That Promotes Wellness 1:00 p.m.–1:45 p.m.

Don’t miss the free chair massages offered daily!

Maximize Your Value and Advocacy to Action

Jennifer Bickel, MD, FAAN, reviews systemlevel strategies to reduce burnout and make professional well-being an organizational priority.

Bickel

Women in Neurology: Thriving Through Challenges 1:00 p.m.–1:45 p.m.

Katherin LaFaver, MD, FAAN, and Divya Singhal, MD, will address common challenges faced by women in neurology in their professional and personal lives, and discuss strategies to thrive amidst difficulties. The presenters will draw from published studies on gender differences in neurology and their personal narratives.

LaFaver

Singhal

US Representative Brendan Boyle (D-PA) provided an update and Q&A on the status of health care legislation under consideration by Congress, including AAN advocacy issues. Boyle and AAN health policy committee leaders, from left, Michael E. Markowski, DO, FAAN, Nicholas E. Johnson, MD, FAAN, Boyle, Brad C. Klein, MD, MBA, FAAN, Glen R. Finney, MD, Jeremy K. Cutsforth-Gregory, MD.

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Tuesday, May 7, 2019 • AANextra

Experience the AAN Check out which of your colleagues are having the most influence on social conversations—and join the conversation yourself at #AANAM!

Innovation Hub Scribes: How to Do It Write 11:30 a.m.–12:00 p.m.

Increasing use of medical scribes is a major trend in offsetting some of the burdens of clinical documentation. Could this work for you and your practice? How does one pay for this service?

Where are the best scribes found? What is the quality of the documentation for clinical care? For billing? What’s the current evidence and experience with scribes? What variations of the scribe concept have been implemented or envisioned? 

Artist and neuroscientist Greg Dunn, PhD, shared his work, “Self Reflected,” which fuses neuroscientific data, hand drawings, algorithmic manipulation, optical engineering, photolithography, and gilding to etch half a million neurons into large sheets of gold.

Tuesday, May 7, 2019 • AANextra

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What’s the key to breakthrough Neuro research and treatments?

Collaboration. At NewYork-Presbyterian Hospital, we partner with specialists

from Columbia University Vagelos College of Physicians and Surgeons and Weill Cornell Medicine to provide care to thousands of neurology and neurosurgery patients. Faculty from both medical schools are at the forefront of conducting research and clinical studies for a wide range of conditions. Recent advances include: Alzheimer’s • A study that uncovered large-scale changes throughout the epigenome of the human Alzheimer’s disease brain, revealing that tau-induced alterations of chromatin structure are more profound than changes attributable to amyloid pathology.

• The launch of our new Alzheimer’s Prevention Clinic that combines evidence-based, low-risk interventions with lifestyle modifications that may help to delay, or in some cases possibly prevent, the progression towards dementia.

Brain Tumors • The first-ever dose escalation study using convection-enhanced delivery for diffuse intrinsic pontine glioma to bypass the blood-brain barrier and administer a drug directly to the brain stem tumor site.

Stroke • Participated in the DEFUSE trial which has shown the benefit of late thrombectomy from 6 to 24 hours past onset of a large vessel occlusive stroke.

Because of these innovations and more, our Neurology and Neurosurgery program is ranked #1 in New York and #5 in the nation by U.S. News & World Report.

Learn more at nyp.org/neuroinnovations

New York’s #1 hospital for a reason.

Source: New York’s #1 hospital as ranked by U.S. News & World Report 2018-19

New AAN Tourette Guideline Shared in Press Conference with World Media The AAN presented its new guideline, “Practice Guideline: The Treatment of Tics in People with Tourette Syndrome and Chronic Tic Disorders,” during yesterday’s press conference with media covering the Annual Meeting. The guideline was published online in Neurology ® on May 6, 2019.

Tamara M. Pringsheim, MD, FAAN, and John Piacentini, PhD, guideline authors, shared findings of the evidence reviewed

by AAN experts. The guideline states there are a variety of treatments available for tics. The guideline provides evidencebased recommendations on the efficacy and safety of the medical, behavioral, and neurostimulation treatments for people with tics, as well as for the assessment of and counseling for these patients. There are approximately 46 recommendations in the clinician summary. Treatment decisions should be individualized to achieve the best balance for each patient.

Choosing among the many treatment options should be done through shared decision making between clinicians and patients.

Comprehensive behavioral intervention for tics has high-quality evidence supporting its efficacy for the treatment of tics, without major adverse effects. It should be made routinely available for individuals with Tourette syndrome. For nondisabling

Pringsheim and Piacentini

tics in children, watchful waiting also is appropriate. Medical interventions for tics are available but should be periodically reassessed because of the high rate of natural remission of tics in late adolescence.

Read the guideline and access summaries for clinicians and families/caregivers and a slide presentation set at AAN.com.

For more information, email guidelines@aan.com or call (612) 928-6069. 

Join Neurology Today at the Annual Meeting Want to learn more about the AAN’s official news source? Stop by the Publications areas on Level 2 across from Registration to check out the latest updates from Neurology Today ®, including a totally revamped, user-friendly website. Enjoy a free cupcake and meet the editor-in-chief today at 11:30 a.m. Also, look for Neurology Today At the Meetings in your email inbox for daily news coverage of the AAN Annual Meeting from May 7 to 10. 

Tuesday, May 7, 2019 • AANextra

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External Validation of Axon Registry Data Demonstrates Value An external audit of the data collected by the AAN’s Axon Registry ® was completed successfully recently, demonstrating the registry is performing as intended and highlighting ways it can be further refined for optimum use.

The Axon Registry is a clinical quality data registry that uses automated data extraction methods from the EHR, and validation of data and processes is critical. Implementation of remediation strategies to improve data accuracy will support the ability of the Axon Registry to perform accurate quality reporting. A prerequisite for the many uses of the Axon Registry is to assure the validity of the data extraction method and to understand the limitations of the data.

To perform the audit of the Axon Registry data, the AAN in 2017 contracted with IQVIA, a highly respected company in the health care industry that has started several registries, serves as a clinical research organization, and performs data analytics. The data validation project was composed of two major phases, where phase one included virtual chart audits of 720 patient charts across nine Axon Registry participating practices. Phase two included measure calculation analysis.

The external validation study revealed that Axon Registry’s data elements match the EHR data elements. For future uses of the registry data, including data analytics and research reports, the Axon Registry data can be trusted to be a surrogate of the source EHR data. The Academy is working with external data analytics centers in preparation for future clinical and health services research study opportunities. Using de-identified data collected via the Axon Registry database, these studies may include assessments of medication effectiveness in post-market surveillance or identification of gaps in care for certain neurologic disease states and evaluation of potential health inequities.

The quality measure calculations performed in phase two of the validation study revealed findings of a moderate degree of agreement in measure performance results between Axon Registry’s calculations and IQVIA’s calculations using the original measure specifications. Considerable variation was found in the degree of agreement across sites, measures, and EHRs. Based on the study, many improvements to registry quality measure processes have been implemented. The validation study was a very useful project and will have lasting and far-reaching impact on quality measure development, practice onboarding, and provider education.

To learn more about the Axon Registry data validation study and results, read the article published in the April 5, 2019, online issue of Neurology ® at NPub.org/AxonData. 

New Web Resource for Academic Institutions The Axon Registry website now has a new section for academic and large institutions that are interested in learning more about the registry. Get answers to your questions and tips on how to promote the Axon Registry to your staff at AAN.com/view/registry.

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Tuesday, May 7, 2019 • AANextra

Demographic data matched more than

90% of the EHR source data

Numbers are statistically significant See article in Neurology® “Axon Registry Data Validation” published April 5, 2019

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Practices

720 Patient Charts

1

Independent Validation

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Daily abstracts of selected key publications in neuroscience Articles written by external leading experts

Expert Talks and scientific presentations by national and international clinicians and scientists

CONFERENCES Highlights of key conferences in neurology

Sign up today! www.neurodiem.com

visit us at the biogen booth to learn more

Neurodiem is a service from Biogen. Biogen-09301 03/19

Leveraging Science as a Tool for Social Change Pediatrician and professor Mona Hanna-Attisha, MD, MPH, had been telling her patients’ parents for months that the water was fine, even though it smelled bad, was rust-colored, and the city had previously had problems with bacteria in the water. The professionals responsible for water safety were taking care of everything.

Once she gathered the research to show that the water in her town of Flint was far from fine, Hanna-Attisha told attendees at the Advancing Medicine: Inspiration and Innovation talk Monday that she could wait no longer.

Hanna-Attisha said that she did what doctors and academics are not supposed to do by releasing the research before it was peerreviewed and published, because the children’s health could not wait.

In response, Hanna-Attisha was attacked and discredited by government officials in the media. Yet with her persistence and her data, the state of Michigan eventually conceded that there was a problem with the water in Flint.

Hanna-Attisha stated that science and scholarship are as powerful tools for social change as art and protest and that individuals working together in a multidisciplinary team can make a difference.

Hanna-Attisha said the story of the water crisis is also an example of the disrespect for science that is occurring now across the country, and a reminder of how intimately the environment is connected to public health.

Outlining the many public health initiatives launched in Flint since the crisis with both public and private funding, Hanna-Attisha said her story is also one of hope. The purpose of science is to improve

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Tuesday, May 7, 2019 • AANextra

our community and to improve the human condition, HannaAttisha said.

The talk captivated Annual Meeting attendees. Jessica Tate, MD, said, “Wonderful talk by @MonaHannaA, and in the neuron dress no less! (Too bad I didn’t wear mine today.)

Such an important story in this age of #sciencedenial and protection of industry over public health and environment!”

“Had the privilege of listening Hanna-Attisha showed off her neuron to @MonaHannaA speak at dress to the room full of neurologists. #AANAM about the Flint Water Crisis. What a phenomenal physician and patient advocate! She is truly an inspiration,” tweeted Ima M. Ebong, MD. The Advancing Medicine: Inspiration and Innovation series concludes with Patricia Churchland, BPhil, leading a compelling discussion on "The Origin of Moral Intuitions" beginning at 1:00 p.m. Wednesday. Throughout her successful career, Churchland has contributed to the fields of neurophilosophy, philosophy of the mind, and neuroethics. Her research has centered on the interface between neuroscience and philosophy with a current focus on the association of morality and the social brain. She is a professor emeritus of philosophy at the University of California, San Diego and adjunct professor at the Salk Institute. 

Want to learn more about AJOVY® (fremanezumab-vfrm) injection?

Visit booth #1729 or AJOVYhcp.com

© 2019 Teva Pharmaceuticals USA, Inc. FRE-41483 March 2019

What excited you today at #AANAM? Natalia S. Rost, MD @nsanar The #FutureOfNeurology is bright #AANAM #MedicalStudent Prize winners are at the @AANMember Plenary stage #WomenInNeurology #WomenInScience

Join the conversation at #AANAM GregWhitman @GregWhitman Got interested in science and medicine partly because of visits I made as a kid to @TheFranklin. While at AAN, you may want to check it out.

Also, have a soft pretzel for me. #AANAM #AANAM2019 Arps @paediatrix Back at the overflow learning area. I love this set up! Its such a blessing for my ADD #FOMO self! #SwitchingChannelsLikeItsTV #AANAM

Leading the way to better patient education

Exclusive Provider of Digital Poster for Contact us today to reserve your complimentary digital poster at customerservice@healthmonitor.com.

Tuesday's AAN Section Meetings 7:00 a.m.–8:00 a.m.

Clinical Neurophysiology Section / 103 A Neurogenetics Section / 103 B

8:15 a.m.–9:15 a.m.

TUESDAY, MAY 7 11:30 A.M. TO 1:00 P.M.

Neuro-ophthalmology/Neuro-otology Section / 103 A Sports Neurology Section / 103 B

12:00 p.m.–1:00 p.m.

Locations: Exhibit Hall C (limited quantities available at Broad Street Atrium)

Stroke and Vascular Neurology Section / 103 A Critical Care and Emergency Neurology Section / 103 B

2:00 p.m.–3:00 p.m.

Neuroendocrinology Section / 103 A Neuroepidemiology Section / 103 B

4:00 p.m.–5:00 p.m.

Neurohealth and Integrative Neurology Section / 103 A

5:00 p.m.–6:00 p.m.

Section Member Reception Poster Hall E – 2nd Level

5:30 p.m.–6:30 p.m.

Child Neurology Section / 103 A

5:45 p.m.–6:45 p.m.

Boxed Lunch Menu Lunch Options Option I:

Option II: Vegan/Vegetarian/Gluten Free

Neuro-infectious Disease Section / 103 B

New! Enjoy Networking Time with Fellow Section Members

Meet your fellow section members and network at the new Section Member Receptions both tonight and Wednesday night from 5:00 p.m. to 6:00 p.m. in the Poster Hall (Exhibit Hall E). Drink tickets and light refreshments will be available for all section members.

Chilled Sumac Salmon Moroccan Rice and Chickpea Salad Roasted Cauliflower Sliced Apples Cinnamon Cookie Chilled Sumac Eggplant Moroccan Rice and Chickpea Salad Roasted Cauliflower Sliced Apples Cinnamon Cookie

Almuerzos con Colegas 12:00 p.m.–12:45 p.m.

Location: Exhibit Hall, zona de almuerzo Reunámonos a comer con colegas hispanoparlantes para charlar sobre temas de interés común. Temas de hoy: Trombectomía en ictus y consejos para obtener empleo en USA: opciones clínicas y extraclínicas.

Tuesday, May 7, 2019 • AANextra

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What Are Your Colleagues Saying?

Share your thoughts at #AANAM. Join the conversation!

#AANAM

Claudia A. Chiriboga, MD, MPH / New York, NY “Why do you come to the Annual Meeting?”

“I come because it is the main general neurology meeting. The main forum to disseminate information to neurologists.”

“What are you most interested in hearing about?”

“The SMA clinical trials and other cutting-edge research. The Emerging Science clinical trials.”

Joel Sullivan / Auburn, AL Medical Student Scholarship recipient “What do you think of the Annual Meeting so far?”

“So far it’s been very informative. I’ve attended courses on career information like what to look for in a residency and how to write a CV. I went to the Medical Student Symposium and met leaders in neurology and other medical students who are interested in neurology.”

LEARN ABOUT A NEW ORAL TREATMENT FOR MULTIPLE SCLEROSIS Visit Booth ©2019 EMD Serono, Inc. All rights reserved.

Printed in the USA US/NPR/0319/0198 03/19

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With hereditary transthyretin-mediated (hATTR) amyloidosis...

Patients and their families face a future of functional decline1-3

Important Safety Information Infusion-Related Reactions (IRRs) In a controlled clinical study, 19% of ONPATTROtreated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).

Please see brief summary of full Prescribing Information following this ad.

References: 1. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013; 8:31. 2. Coutinho P, Martins da Silva A, Lopes Lima JL, et al. Excerpta Medica; 1980:88-98.

3. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119. 4. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2018.

5. Adams D, Coelho T, Obici L, et al. Neurology. 2015;85(8):675-682. 6. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21. 7. Center for Drug Evaluation and Research. NDA 210922—patisiran—cross-discipline team leader review. U.S. Department of Health and Human Services, Food and Drug Administration; 2018.

ONPATTRO is a registered trademark of Alnylam Pharmaceuticals, Inc. © 2019 Alnylam Pharmaceuticals, Inc. All rights reserved. TTR02-USA-00023-012019

ONPATTRO® (patisiran) can reverse polyneuropathy manifestations of the disease4 A novel RNAi-based approach that may transform the future for your patients1,4-6 ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

At 18 months, ONPATTRO demonstrated: Reversal in neuropathy impairment4

Study Design The efficacy of ONPATTRO was demonstrated in a randomized, double-blind, placebo-controlled, multicenter clinical trial in adults with hATTR amyloidosis with polyneuropathy. Patients were randomized to receive ONPATTRO 0.3 mg/kg (N=148) or placebo (N=77) via intravenous infusion once every 3 weeks for 18 months.

Primary endpoint: The modified Neuropathy Impairment Score + 7 (mNIS+7) is an objective 304-point assessment of neuropathy that measures cranial nerve function, muscle strength, reflexes, postural blood pressure, quantitative sensory testing, and peripheral nerve electrophysiology.

Key secondary endpoint: The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) scale is a patient-reported assessment that evaluates neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy (score range -4 to 136).

Select secondary endpoint: The Composite Autonomic Symptom Score 31 (COMPASS 31) is a patient-reported questionnaire that evaluates 6 autonomic domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor (score range 0 to 100).

• Mean change from baseline in mNIS+7 of -6.0 points vs 28.0 with placebo, a treatment difference of -34 points (95% CI: -39.9, -28.1; p<0.001)

Improvement in quality of life4 • Mean change from baseline in Norfolk QoL-DN score of -6.7 points vs 14.4 with placebo, a treatment difference of -21.1 points (95% CI: -27.2, -15.0; p<0.001)

Reduction in autonomic symptoms6,7 • Mean change from baseline in COMPASS 31 of -5.3 points vs 2.2 with placebo, a treatment difference of -7.5 points (95% CI: -11.9, -3.2; p<0.001) CI=confidence interval; RNA=ribonucleic acid; RNAi=RNA interference.

Visit Booth #2401 to find out more.

Today Is National Institutes of Health Day in the Research Corner Experiential Learning Area Head on over to Research Corner Experiential Learning Area for a full-day’s lineup of all-things National Institutes of Health (NIH).

The day will kick off this morning at 8:00 a.m. with a welcome and overview of funding with the directors from the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Aging (NIA). Programming throughout the day will offer chances to learn about funding opportunities, the grant review process, clinical trials, and more.

NIH Day Schedule:

Koroshetz

:00 a.m.–8:45 a.m.

8 Welcome to NIH Day/ Overview of NIH Funding NINDS Director Walter J. Koroshetz, MD, FAAN; and NIA Director, Division of Neuroscience, Eliezer Masliah, MD

12:00 p.m.–12:30 p.m.

1:45 p.m.–2:15 p.m.

NIH Funding and Professional Development Opportunities for Diverse Researchers Michelle Jones-London, PhD, NINDS

2:15 p.m.–3:00 p.m.

Clinical Trials and Networks—NeuroNEXT, StrokeNET, SIREN; Alzheimer’s Clinical Trials Consortium Clinton Wright, MD, NINDS; Eliezer Masliah, MD, NIA

3:00 p.m.–3:45 p.m.

AD/ADRD Opportunities Clinton Wright, MD, NINDS; Eliezer Masliah, MD, NIA

3:45 p.m.–4:30 p.m.

HEAL Initiative—Pain Research Funding Opportunities, Clinical and Basic Michael Oshinsky, PhD, NINDS; Linda Porter, PhD, NINDS

4:30 p.m.–5:00 p.m.

Translational Research Amir Tamiz, PhD, NINDS 

Learn About Opportunities to Work with the NIH Intramural Program Avi Nath, MD, NINDS

12:30 p.m.—1:00 p.m.

NIH Grant Review Process Shanta Rajaram, PhD, NINDS

1:00 p.m.–1:45 p.m.

K Awards and Training Programs—Planning for a Career as an NIH Investigator Nina Schor, MD, PhD; Adam Hartman, MD

Enhance Your Annual Meeting Experience with Digital Library With so many robust education offerings during the Annual Meeting, it is impossible to attend every course you are interested in. Luckily, Annual Meeting On Demand has you covered!

This comprehensive, CME-accredited digital library allows you to: NEW! Access quickly and easily from the AAN’s Online

Learning Center, the new, streamlined, centralized hub for all AAN online learning offerings*

Pre-order by May 10 to save $150!

In Person: Visit the eLearning Networking and Innovation Space, Arch Street Atrium Online: AAN.com/view/19AMOD

Watch 500+ hours** of presentations like you’re there in

person with slides and synchronized audio

Access 200+ programs and syllabi within 24 hours of the

completion of the live presentation

Learn at home, the office, or on the go Earn credits with integrated CME testing  * With the move to an online offering, hard drives will not be provided. ** Specific presentations within a session may not be available or may be audio only if the presenter has confidential patient information or otherwise declines to be recorded.

Tuesday, May 7, 2019 • AANextra

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Board Member Gains Valuable Insight, Satisfaction Through Leadership Program “It was a fantastic experience!”

This response comes easily for Charlene Gamaldo, MD, FAAN, FAASM, when asked to sum up her feelings about the AAN’s Transforming Leaders Program.

The 2016-2017 participant credits the 11-month opportunity with helping her recognize and appreciate the importance of identifying strengths—not only in herself, but also in others—and Gamaldo optimizing those strengths to achieve personal and professional development, satisfaction, and common goals.

“Specifically, I found these skills helpful as I worked with my team to open a new sleep center,” said Gamaldo of the group project she and co-participants tackled as a requirement of the program.

“The project called for adaptability in a changing health care climate, innovative ideas, and measured execution of plans to stay ahead of the game. What I learned from program mentors helped me to better appreciate and communicate with my team.”

Gamaldo’s new skills have proven equally useful in her daily life as a faculty member of the Johns Hopkins School of Medicine’s neurology, psychiatry, nursing, anesthesiology, and public health departments, as well as her role as medical director of the Johns Hopkins Center for Sleep and vice chair for faculty development for the neurology department. “My experience with Transforming

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Tuesday, May 7, 2019 • AANextra

Leaders has been helpful in mentoring our faculty as we address strategies for identifying their paths to career growth and satisfaction—based on developing their strengths, and not harping on limitations. It has also served as an important method to tackle burnout.”

After several years of committee work and other volunteer involvement with the AAN, Gamaldo was elected to the AAN Board of Directors in April 2017, a role in which she’s finding plenty of opportunity to leverage her Transforming Leaders training. “Transforming Leaders gave me a firsthand look at the inner workings of the Academy, the organizational mission, and the diverse effort and infrastructure involved to achieve our goal of ‘being indispensable to members.’ With the insight gained regarding methods to optimize my leadership effectiveness and my heightened pride in the efforts of the Academy, I feel poised to put my best foot forward in contributing to the Board, members of the Academy, and our field.”

Gamaldo also sees the power of the program extending beyond leadership skills to mental, physical, and spiritual well-being.

“Involvement in one’s professional organizations has been linked to less burnout and greater professional satisfaction,” she said. “The Transforming Leaders Program not only gives you a greater appreciation for what the Academy is about and the ongoing efforts, initiatives, and avenues that may be available to contribute to the field of neurology, but it feeds your personal and professional soul. In this busy world and hectic medical landscape, the Transforming Leaders Program forces you to take the invaluable opportunity to exhale, reflect, and think about

your personal goals, strengths, development, and overarching path to satisfaction. Quite honestly, I am not sure if I would have taken even a fraction of the time to contemplate those issues if it weren’t for Transforming Leaders.”

The Transforming Leaders Program has been supported in part

by Allergan, Inc., Lundbeck LLC, Neurocrine Biosciences, Sanofi Genzyme, and Supernus Pharmaceuticals, Inc.

Applications Now Open for Four AAN Leadership Program Opportunities Applications are open to AAN members until June 17 for four empowering opportunities designed specifically to equip participants with the skills, tools, and confidence to successfully tackle the challenges that lie ahead.

Past participants of these all-expenses-paid programs have found them to be incredibly valuable, citing the personalized coaching with industry leading consultants, mentorship by neurology leaders, and expansion of professional network as particularly impactful.

Transforming Leaders - Designed to help innovative leaders

realize their goals through executive-level coaching and a fully customized intensive leadership development training program.

Women Leading in Neurology - An empowering and

inspirational leadership development opportunity designed to tackle gender disparities head-on and help women leaders advance to the top levels of leadership in their fields and within the AAN.

Emerging Leaders - Designed to identify, engage, and

mentor talent among early-career members interested in future leadership roles within the AAN and the field of neurology.

Practice Leadership - Designed to identify and engage solo

and small practitioners interested in helping to shape the future of neurology within the AAN and/or their communities.

The program’s flexible schedule easily accommodates the restricted schedules of busy practitioners.

Visit AAN.com/view/LEAD to learn more or apply by the June 17 deadline. 

Tuesday, May 7, 2019 • AANextra

21

THE FIRST FDA-APPROVED TREATMENT INDICATED FOR ADULTS WITH TARDIVE DYSKINESIA (TD)1

ONE CAPSULE, ONCE DAILY1 Convenient, once-daily dosing without complex titration1

Not actual size

• INGREZZA 80 mg provided rapid and significant reductions in TD severity by 6 weeks1,2 —with continued reductions in TD severity through 48 weeks1,3 • Generally well tolerated in clinical trials across a broad range of adult TD patients1,2 • Selectively inhibits VMAT2, with no appreciable binding affinity for serotonergic or dopaminergic receptors1 • Offers convenient, once-daily dosing without complex titration1 VMAT2, vesicular monoamine transporter 2.

Not an actual patient

I S I T T D O R A C U T E E P S ? | TA K E T H E T D C H A L L E N G E AT B O OT H # 9 0 0 EPS, extrapyramidal symptoms.

W W W. I N G R E Z Z A H C P. C O M

Important Information INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

WARNINGS & PRECAUTIONS Somnolence

INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

QT Prolongation

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

ADVERSE REACTIONS

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see the adjacent page for brief summary of Prescribing Information and visit www.INGREZZAHCP.com/PI for full Prescribing Information.

REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc; 2018. 2. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484. 3. Factor SA, Remington G, Comella CL, et al. The effects of valbenazine in participants with tardive dyskinesia: results of the 1-Year KINECT 3 extension study. J Clin Psychiatry. 2017;78(9):1344-1350.

©2019 Neurocrine Biosciences, Inc. All Rights Reserved. CP-VBZ-US-0525v2 5/19

for oral use

Brief Summary: for full Prescribing Information and Patient Information, refer to package insert.

INDICATIONS AND USAGE

Endocrine Disorders: blood glucose increased General Disorders: weight increased Infectious Disorders: respiratory infections Neurologic Disorders: drooling, dyskinesia, extrapyramidal symptoms (non-akathisia) Psychiatric Disorders: anxiety, insomnia During controlled trials, there was a dose-related increase in prolactin. Additionally, there was a dose-related increase in alkaline phosphatase and bilirubin, suggesting a potential risk for cholestasis.

Postmarketing Experience

INGREZZA® is indicated for the treatment of adults with tardive dyskinesia.

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

WARNINGS AND PRECAUTIONS Somnolence

INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

QT Prolongation INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA concentrations may be higher and QT prolongation clinically significant. For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary. For patients taking a strong CYP3A4 inhibitor, reduce the dose of INGREZZA to 40 mg once daily.

INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

The following adverse reactions have been identified during post-approval use of INGREZZA that are not included in other sections of labeling. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: hypersensitivity reactions (including allergic dermatitis, angioedema, pruritis, and urticaria) Skin and Subcutaneous Tissue Disorders: rash

DRUG INTERACTIONS

Drugs Having Clinically Important Interactions with INGREZZA Table 2: Clinically Significant Drug Interactions with INGREZZA Monoamine Oxidase Inhibitors (MAOIs) Clinical Implication: Concomitant use of INGREZZA with MAOIs may increase the concentration of monoamine neurotransmitters in synapses, potentially leading to increased risk of adverse reactions such as serotonin syndrome, or attenuated treatment effect of INGREZZA. Prevention or Avoid concomitant use of INGREZZA with MAOIs. Management:

ADVERSE REACTIONS

Examples: isocarboxazid, phenelzine, selegiline Strong CYP3A4 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP3A4 inhibitors increased the exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of INGREZZA alone.

Increased exposure of valbenazine and its active metabolite may increase the risk of exposure-related adverse reactions.

Prevention or Reduce INGREZZA dose when INGREZZA is coadministered with a strong CYP3A4 inhibitor.

Management:

The following adverse reactions are discussed in more detail in other sections of the labeling: • Hypersensitivity • Somnolence • QT Prolongation

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Variable and Fixed Dose Placebo-Controlled Trial Experience The safety of INGREZZA was evaluated in 3 placebo-controlled studies, each 6 weeks in duration (fixed dose, dose escalation, dose reduction), including 445 patients. Patients were 26 to 84 years of age with moderate to severe tardive dyskinesia and had concurrent diagnoses of mood disorder (27%) or schizophrenia/ schizoaffective disorder (72%). The mean age was 56 years.

Patients were 57% Caucasian, 39% African-American, and 4% other. With respect to ethnicity, 28% were Hispanic or Latino. All subjects continued previous stable regimens of antipsychotics; 85% and 27% of subjects, respectively, were taking atypical and typical antipsychotic medications at study entry.

Adverse Reactions Leading to Discontinuation of Treatment A total of 3% of INGREZZA treated patients and 2% of placebo-treated patients discontinued because of adverse reactions.

Common Adverse Reactions Adverse reactions that occurred in the 3 placebo-controlled studies at an incidence of ≥2% and greater than placebo are presented in Table 1.

Table 1:

Adverse Reactions in 3 Placebo-Controlled Studies of 6-week Treatment Duration Reported at ≥2% and >Placebo

Adverse Reaction1

Examples: Strong CYP3A4 Inducers Clinical Implication:

paroxetine, fluoxetine, quinidine

Prevention or Management:

Concomitant use of strong CYP3A4 inducers with INGREZZA is not recommended. rifampin, carbamazepine, phenytoin, St. John’s wort1

Digoxin concentrations should be monitored when co-administering INGREZZA with digoxin. Increased digoxin exposure may increase the risk of exposure related adverse reactions. Dosage adjustment of digoxin may be necessary.

INGREZZA (n=262) (%)

Placebo (n=183) (%)

General Disorders Somnolence (somnolence, fatigue, sedation)

10.9%

4.2%

Examples: Digoxin Clinical Implication:

Nervous System Disorders Anticholinergic effects (dry mouth, constipation, disturbance in attention, vision blurred, urinary retention)

5.4%

4.9%

Prevention or Management:

Balance disorders/fall (fall, gait disturbance, dizziness, balance disorder)

4.1%

2.2%

Headache Akathisia (akathisia, restlessness)

3.4% 2.7%

Gastrointestinal Disorders Vomiting Nausea Musculoskeletal Disorders Arthralgia 1

Examples: itraconazole, ketoconazole, clarithromycin Strong CYP2D6 Inhibitors Clinical Implication: Concomitant use of INGREZZA with strong CYP2D6 inhibitors may increase the exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of INGREZZA alone. Increased exposure of active metabolite may increase the risk of exposurerelated adverse reactions.

Prevention or Consider reducing INGREZZA dose based on tolerability when INGREZZA is coadministered with a strong CYP2D6 inhibitor.

Management:

2.7% 0.5%

1

Concomitant use of INGREZZA with a strong CYP3A4 inducer decreased the exposure of valbenazine and its active metabolite compared to the use of INGREZZA alone. Reduced exposure of valbenazine and its active metabolite may reduce efficacy.

Concomitant use of INGREZZA with digoxin increased digoxin levels because of inhibition of intestinal P-glycoprotein (P-gp).

The induction potency of St. John’s wort may vary widely based on preparation.

Drugs Having No Clinically Important Interactions with INGREZZA Dosage adjustment for INGREZZA is not necessary when used in combination with substrates of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5 based on in vitro study results.

OVERDOSAGE

Human Experience 2.6% 2.3%

0.6% 2.1%

2.3%

0.5%

Within each adverse reaction category, the observed adverse reactions are listed in order of decreasing frequency.

Other Adverse Reactions Observed During the Premarketing Evaluation of INGREZZA

Other adverse reactions of ≥1% incidence and greater than placebo are shown below. The following list does not include adverse reactions: 1) already listed in previous tables or elsewhere in the labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have clinically significant implications, or 5) which occurred at a rate equal to or less than placebo.

The pre-marketing clinical trials involving INGREZZA in approximately 850 subjects do not provide information regarding symptoms with overdose.

Management of Overdosage No specific antidotes for INGREZZA are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement. If an overdose occurs, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org).

For further information on INGREZZA, call 84-INGREZZA (844-647-3992).

Distributed by: Neurocrine Biosciences, Inc. San Diego, CA 92130 INGREZZA is a registered trademark of Neurocrine Biosciences, Inc. CP-VBZ-US-0203v3 08/18

AAN Advocacy Continues to Push Neuro Research Funding Higher After years of flat or declining funding, Congress prioritized medical research at the National Institutes of Health during the last three budget cycles, thanks, in part, to intense lobbying by the AAN and its members. The federal FY2018 omnibus spending bill included more than $2 billion in increased spending on brain research.

In September 2018, Congress passed the FY2019 LaborEducation-HHS budget, and again AAN advocacy helped pave the way for significant research increases, including: $39.1 billion for NIH, a $2 billion increase $2.22 billion for NINDS, a $71.77 million increase $2.34 billion for Alzheimer’s disease research, a $425

million increase

$429 million for the BRAIN Initiative, a $29 million increase Opioids: $500 million in dedicated funding for research related

to opioid addiction, development of opioid alternatives, pain management, and addiction treatment. Funding is provided equally to NINDS and the National Institute on Drug Abuse.

The committee notes that this is in addition to the $774 billion NIH is expected to spend in base funding for opioid misuse and addiction treatment as well as pain research. $7.9 billion for the Centers for Disease Control and Prevention,

which, after removing a one-time funding allocation completed in FY2018, is comparable to last year’s budget, and includes $5 million for National Neurological Conditions Surveillance System

24

Tuesday, May 7, 2019 • AANextra

Education and Personal Experiences Help Create Congressional Allies These increases are not solely the result of pressure from AAN leadership and staff. Concerned members like Clifton L. Gooch, MD, FAAN, are stepping forward to educate lawmakers, helping to distill dry budget appropriations and complex science into highly personal terms for his district congressman, Rep. Gus Bilirakis (R-FL).

“I was pleased to host Congressman Bilirakis here at the University of South Florida,” said Gooch, “and gave him a presentation which outlined the coming epidemic in neurological diseases (using my burden of disease article in the February 15, 2017, Annals of Neurology). I then proceeded to make the case for greater funding for neurological research and advocacy, while thanking him for his pivotal involvement in supporting NIH funding and getting the 21st Century Cures Act passed. We then had a nice roundtable discussion regarding how the NIH might be better focused on translational research to find neurological cures, among other topics. I also advocated for him to help us in our fight against the new CMS coding change proposals, which would be devastating for neurology. He was very receptive and is a great advocate for us; his brother has Parkinson's and his mother has advanced Alzheimer's, so he has been personally touched by these issues.”

Establishing Trust Can Make a Difference David Q. Beversdorf, MD, FAAN, conducts brain research at the University of Missouri. He has participated in the AAN’s Neurology on the Hill and the Palatucci Advocacy Leadership Forum, and contributes to the Academy’s BrainPAC political action committee to help educate members of Congress. He’s also been involved in other advocacy activities, such as the Rally for Medical Research, the Society for Neuroscience Hill Day, and the Society for Neuroscience Government and Public Affairs Committee. He shared his tactics to promote increased research funding with one of his state’s senators in a recent Capitol Hill Report.

“Over the years, you can build relationships with the teams supporting your elected officials. You can also serve as a resource for them for related issues. Additionally, you will serve as a trusted source for them when a new issue comes up. This has been helpful when issues have arisen that affect us as clinicians, such as the recently proposed E/M changes, where I am able to have a strong voice due to building a relationship.”

Beversdorf continued, “It is also important to recognize the positions held by your elected officials. Sen. Roy Blunt from Missouri is chair of the committee responsible for allocating the budget for NIH. He has been a staunch supporter for biomedical research. He is to a great extent responsible for the recent increases in NIH funding. I make a point to reach out to his team, and they have come to know me in this role. This leads to the final point. SAY THANK YOU! Sometimes the decisions made by our representatives come with some heat from some of their varied constituents. They need to know, in no uncertain terms, how much their efforts are appreciated when they support us in our needs! Thanks to these very representatives, federal funding in research has taken a significant positive turn in the last few years. Educating them about its importance is up to us, as well as communicating our appreciation for their support. I believe that the combined efforts of the research community in this regard has contributed to this outcome.”

From left: Stephen B. Liggett, MD, USF associate vice president for research; Rep. Gus Bilirakis; Clifton L. Gooch, MD, FAAN, chair of USF neurology; Glenn Currier, MD, MPH, chair of USF psychiatry.

Federal Funding Pivotal to BRAIN Initiative Research At the University of Alabama-Birmingham, AAN member Harrison C. Walker III, MD, is the principal investigator for a grant from the BRAIN Initiative, which the Academy has championed since it was launched by the Obama administration in 2013.

Walker’s five-year, $7.3 million grant, which began in November 2016, focuses on directional vs. circular deep brain stimulation (DBS) to help treat Parkinson’s disease. He also receives funding from the Michael J. Fox Foundation to understand and treat dystonia related to Parkinson’s with DBS. “Foundation funding is great for feasibility testing. The AAN and other foundations provide critical support that lay the groundwork for larger studies,” said Walker, who is one of several people at UAB working on the BRAIN Initiative-supported research.

“The BRAIN Initiative is unique in that it focuses on advancing neuromodulation technologies in patients, both for established and emerging indications. This programmatic focus has opened doors for human studies that were less accessible under traditional funding mechanisms. This research is critical to translate advances from all levels of neuroscience into clinical practice.”

To Walker, a donor to the AAN’s BrainPAC political action committee, “Advocacy is the biggest benefit of the AAN.” And it is a benefit that can, and will, help millions of lives beyond the AAN’s membership. 

It’s EASY Bein’ Green!

The green bowties and scarves you see today on AAN members at the Advocacy ELA denote their participation in advocacy events such as Neurology on the Hill. Ask them how easy it is “bein’ green” and fighting for the issues that affect neurologists and their patients. Snap a picture of yourself and these leaders and post them on social media using the tags @AANmember, #AANAdvocacy, and #AANAM.

Tuesday, May 7, 2019 • AANextra

25

NOW

AVA IL A B LE

Finally, there’s a whole new path to explore

Booth 2129 Follow the footprints in the exhibit hall and discover EPIDIOLEX® (cannabidiol) Cv

Greenwich Biosciences is growing innovation Step into the growing and manufacturing process with a virtual reality experience at the booth.

Visit EPIDIOLEXhcp.com for more information

©2019 Greenwich Biosciences Inc. All rights reserved. EPX-04965-0319

The Best of Philly from Those Who Know It Best As America’s birthplace, Philadelphia is the nation’s first World Heritage City, not to mention the home of the first medical school and first neurology program. Where else can you walk from the sites where political luminaries debated standing up to a king to the home of one of the largest collections of Rodin sculptures outside of Paris before making your way to grab an authentic hoagie?

Visit the Philadelphia visitors booths (Broad Street Atrium, spiral staircase on the 200 Level Bridge, or 12 and Arch Street- West Concourse) for more local information, including brochures and help making restaurant reservations. 

Need some ideas? Here you go!

So many hot spots in Philly, so little time! There's plenty of fun for the whole family: See the birthplace of American democracy, or as we lovingly call it Independence National Historical Park (INHP),

where you can stand next to the beautiful bronze Liberty Bell.

Then stroll across the street and see Independence Hall, home to the signing of the Declaration of Independence

and the Constitution.

Check out the Philadelphia Zoo, America’s first zoo!

Next stop, The Franklin Institute, known as one of the leading science centers in the country showcasing life

sciences, from sports to space and beyond.

Head on over to The Philadelphia Museum of Art, forever remembered in the classic film Rocky. Grab your bottle

of water and take a run up the “Rocky Steps!”

Then check out the amazing art collection comprised of art from across the world— including American,

Renaissance, Asian, impressionist, and contemporary masterpieces.

A special treat for those of all ages is one of the nation’s top children’s museums, the Please Touch Museum… and

by all means, PLEASE TOUCH!

How about checking out Philadelphia’s own Academy of Natural Sciences, which is more than 200 years old and

known as America’s oldest natural history museum.

Want more?

Visit the birthplace of the first Stars and Stripes at the Betsy Ross House.

The Mütter Museum is a must see for anyone in health care. It is a tour of the fascinating and the anatomically

strange. See a wide array of preserved abnormal body parts along with skeletal formations and captivating specimens. Ripley’s has nothing on this museum!

Looking for something different, feel free to stop by Al Capone’s place of residence, the former prison, Eastern State Penitentiary, a great place to visit on Halloween. It’s the scariest haunted house ever!

Are you a foodie or food snob? We got you covered. Choose your chef or restauranteur: Stephen Starr, Michael

Shulson, Marcie Turney & Valerie Safran, Marc Vetri, Nicholas Elmi, Michael Solomonov, or Jose Garces. Look up their many restaurants. The choices and quality are hard to beat.

The list goes on and on. For culture, fine dining and the arts, Philadelphia has it all!

—Brad C. Klein, MD, MBA, FAAN

Abington Neurological Associates, Willow Grove, PA Chair, Medical Economics and Practice Committee Ex officio voting member, AAN Institute Board of Directors

What are your Philly recommendations?

Join the conversation at #AANAM

Tuesday, May 7, 2019 • AANextra

27

Find the Latest Research at Today’s Poster Session Today’s poster session runs from 11:30 a.m. to 6:30 p.m., with author standby taking place daily between 5:30 p.m. and 6:30 p.m. To help you navigate your way to the breakthrough research of most interest to you, each of the five sessions in this year’s hall are arranged in 10 topicrelated “neighborhoods.” The example below shows how making your way to your favorite poster is now as easy as 1-2-3. In addition, tours of similar-themed posters will occur daily during the poster hall’s open hours to help visitors focus in on their areas of interest. 

Check out what’s in each neighborhood during today’s poster session:

Publication Code Example: P3.2-003 • P3 = Poster Session Number • 2 = Neighborhood • 003 = Poster Board Number

Poster Session 3 1. Aging, Dementia, Cognitive, and Behavioral Neurology: 1-001 to 1-031 2. MS and CNS Inflammatory Disease: 2-001 to 2-103 3. Cerebrovascular Disease and Interventional Neurology: 3-001 to 3-071 4. Neuromuscular Disease and Clinical Neurophysiology (EMG): 4-001 to 4-046 5. Epilepsy/Clinical Neurophysiology (EEG): 5-001 to 5-033 6. Neuro-oncology; Sleep; Autonomic Disorders; Child Neurology and Developmental Neurology: 6-001 to 6-070 7. Neuromuscular Disease and Clinical Neurophysiology (EMG) ePosters: 7-001 to 7-010 8. Movement Disorders: 8-001 to 8-052 9. Neurocritical Care; Neuro Trauma and Sports Neurology; General Neurology: 9-001 to 9-079 10. Headache: 10-001 to 10-026

1 2 3

1-001-1-031

2-001-2-103

3-001-3-071

4 5 6

4-001-4-046

5-001-5-033

6-001-6-070

7

7-001-7-010

ePosters

8 9 10

8-001-8-052

9-001-9-079

10-001-10-026

Movement Disorders Featured in Today's Invited Science Session Continued from cover

Abstracts and authors include: 3:30 p.m.–3:55 p.m.

LRP10 Genetic Variants in PD Wim Mandemakers, PhD, Rotterdam, Netherlands

3:55 p.m.–4:20 p.m.

Predicting Alpha-synuclein Pathology by RBD David Shprecher, DO, Sun City, AZ

4:20 p.m.–4:45 p.m.

Caregiver Burden in PD Nabila Dahodwala, MD, Philadelphia, PA

4:45 p.m.–5:05 p.m.

Subtypes and Neural Networks Using PPMI Fei Wang, PhD, New York, NY

5:05 p.m.–5:30 p.m.

Closed Loop Spinal Cord Stimulation Amol Yadav, PhD, Durham, NC 

28

Tuesday, May 7, 2019 • AANextra

Is Your Alumni Group Getting Together?

Are you looking to connect, reunite, and collaborate with colleagues at any of the many In Conjunction With (ICW) meetings going on this week, including staff and board meetings, alumni reunions, and social dinners? Be sure to refer to the Annual Meeting On-site Guide for a full listing of meetings and times— and note that most alumni reunions are occurring tonight! 

INDUSTRY THERAPEUTIC UPDATE FROM AVEXIS A NEW FRONTIER FOR NEUROMUSCULAR DISORDERS: SPOTLIGHT ON GENE THERAPY Wednesday May 8 2019, 7:00 PM for 7:30 PM start* Room: Liberty Ballroom, Philadelphia Marriott Downtown

Faculty:

Perry Shieh, MD, PhD (Chair) Meredith Schultz, MD Christopher Walker, PhD Chris Jenkins, PhD *Dinner to be served at 7:00 PM

The Faculty of experts will explore the latest advances in gene therapy (GT) research and the use of GT in the clinical treatment of neuromuscular diseases, taking the treatment from bench to bedside.

Time

Presentation Title

Faculty Member

7:00 – 7:30 PM

Dinner reception

7:30 – 7:35 PM

Welcome and introduction

Perry Shieh, MD, PhD (Chair)

7:35 – 7:55 PM

Gene therapies: a new frontier for neuromuscular disorders

Meredith Schultz, MD

7:55 – 8:15 PM

A focus on adeno-associated virus (AAV) antibodies

Christopher Walker, PhD

8:15 – 8:35 PM

Biosafety considerations for the clinical use of AAVs

Chris Jenkins, PhD

8:35 – 8:45 PM

Panel discussion

All Speakers Facilitated by Chair

8:45 – 8:55 PM

Questions and answers

All Speakers Facilitated by Chair

8:55 – 9:00 PM

Closing remarks

Perry Shieh, MD, PhD (Chair)

In accordance with Federal Law, all food and beverage are reportable. You will have the opportunity to opt-out of food and beverage upon arrival at the Liberty Ballroom, Philadelphia Marriott Downtown This meeting is not part of the AAN Annual Meeting official programming and no CME is given for attendance.

This Industry Therapeutic Update is sponsored and organized by AveXis. ©2019 AveXis, Inc. All Rights Reserved.

MED-CON-UNB-00019-US 04/2019

Important Clinical Trials Showcased in this Morning's Plenary Continued from cover

SPRINT MIND: Results Update and Future Directions Jeff Williamson, MD Wake Forest Baptist Health, Wake Forest, NC

Randomized Controlled Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder Bruce A.C. Cree, MD, PhD, MCR, FAAN University of California, San Francisco, Multiple Sclerosis Center, San Francisco, CA

Intravenous Immunoglobulin to Prevent Myasthenic Crisis After Thymectomy and Other Surgical Procedures Can Be Omitted: A Randomized, Controlled, Double-blind Trial

A Placebo-Controlled Study of Galcanezumab in Patients with Episodic Cluster Headache: Results from the 8-week Double-blind Treatment Phase David W. Dodick, MD, FAAN Mayo Clinic Arizona, Scottsdale, AZ

Use of Tranexamic Acid in Patients with Traumatic Brain Injury: Results from the North American Multi-Center Prehospital TXA for TBI Trial Susan Rowell, MD, MCR Oregon Health & Science University, Portland, OR

From Bench to Bedside to Beam: Hippocampal-sparing During Brain Irradiation

Josep Gamez, MD, PhD Hospital Universitari Vall D’Hebron, Barcelona, Spain

Vinai Gondi, MD Radiation Oncology Consultants, Chicago, IL

rAAV2/2-ND4 for the Treatment of LHON: 72-week Data from the REVERSE Phase III Clinical Trial

A Phase 3 Study of Isradipine as a Disease-Modifying Agent in Patients with Early Parkinson’s Disease (STEADY-PD III): Final Study Results

Mark L. Moster, MD, FAAN Wills Eye Hospital, Philadelphia, PA

Tanya Simuni, MD On behalf of the Parkinson Study Group / Northwestern University Feinberg School of Medicine, Chicago, IL

What is your "aha" moment from the Clinical Trials Plenary Session? Join the conversation at #AANAM. 

30

Tuesday, May 7, 2019 • AANextra

VISIT US AT BOOTH #1413 I N P A R T I A L - O N S E T S E I Z U R E S 1…

The mountains of evidence support one powerful MONOTHERAPY choice2,3

11 POSITIVE

CLINICAL TRIALS FOR THE TREATMENT OF PARTIAL-ONSET SEIZURES2,3

guaranteed, for a minimum of 12 months* www.OxtellarXRhcp.com

INDICATION Oxtellar XR® is indicated for the treatment of partial-onset seizures in patients 6 years of age and older.

CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, or to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema. *Terms and conditions apply.

Not actual patient. Fictionalized for illustrative purposes.

References: 1. Oxtellar XR [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc.; December 2018. 2. Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21(8):904-919. 3. French JA, Baroldi P, Brittain ST, Johnson JK; for PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014;129:143-153.

Please refer to the brief summary of full Prescribing Information on adjacent pages, or visit www.OxtellarXR.com.

Oxtellar XR is a registered trademark of Supernus Pharmaceuticals, Inc. ©2019 Supernus Pharmaceuticals, Inc. All rights reserved. SPN.OXT.2019-0023

Powerfully evident choice

OXTELLAR XR® (oxcarbazepine) extended-release tablets, for oral use Brief Summary of Prescribing Information For full prescribing information, see Package Insert.

CONTRAINDICATIONS Oxtellar XR is contraindicated in patients with a known hypersensitivity to oxcarbazepine, to any of the components of Oxtellar XR, or to eslicarbazepine acetate. Reactions have included anaphylaxis and angioedema.

WARNINGS AND PRECAUTIONS Hyponatremia Clinically significant hyponatremia (sodium <125 mmol/L) may develop during Oxtellar XR® use. Serum sodium levels less than 125 mmol/L have occurred in immediate-release oxcarbazepine-treated patients generally in the first three months of treatment. However, clinically significant hyponatremia may develop more than a year after initiating therapy.

Most immediate-release oxcarbazepine-treated patients who developed hyponatremia were asymptomatic in clinical trials. However, some of these patients had their dosage reduced, discontinued, or had their fluid intake restricted for hyponatremia. Serum sodium levels returned toward normal when the dosage was reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).

Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during post-marketing use of immediate-release oxcarbazepine.

Among treated patients in a controlled trial of adjunctive therapy with Oxtellar XR® in 366 adults with complex partial seizures, 1 patient receiving 2400 mg experienced a severe reduction in serum sodium (117 mEq/L), requiring discontinuation from treatment, while 2 other patients receiving 1200 mg experienced serum sodium concentrations low enough (125 and 126 mEq/L) to require discontinuation from treatment. The overall incidence of clinically significant hyponatremia in patients treated with Oxtellar XR® was 1.2%, although slight shifts in serum sodium concentrations from Normal to Low (<135 mEq/L) were observed for the 2400 mg (6.5%) and 1200 mg (9.8%) groups compared to placebo (1.7%).

Measure serum sodium concentrations if patients develop symptoms of hyponatremia (e.g., nausea, malaise, headache, lethargy, confusion, obtunded consciousness, or increase in seizure frequency or severity). Consider measurement of serum sodium concentrations during treatment with Oxtellar XR®, particularly if the patient receives concomitant medications known to decrease serum sodium levels (for example, drugs associated with inappropriate ADH secretion).

Anaphylactic Reactions and Angioedema Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported in patients after taking the first or subsequent doses of immediate-release oxcarbazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with Oxtellar XR®, discontinue the drug and initiate an alternative treatment. Do not rechallenge these patients with Oxtellar XR®.

Cross Hypersensitivity Reaction to Carbamazepine Approximately 25% to 30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with Oxtellar XR®. For this reason, patients should be specifically questioned about any prior experience with carbamazepine, and patients with a history of hypersensitivity reactions to carbamazepine should ordinarily be treated with Oxtellar XR® only if the potential benefit justifies the potential risk. Discontinue Oxtellar XR® immediately if signs or symptoms of hypersensitivity develop.

Serious Dermatological Reactions Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in both children and adults treated with immediate-release oxcarbazepine use.

The median time of onset for reported cases was 19 days. Such serious skin reactions may be life threatening, and some patients have required hospitalization with very rare reports of fatal outcome. Recurrence of the serious skin reactions following rechallenge with immediate-release oxcarbazepine has also been reported.

The reporting rate of TEN and SJS associated with immediaterelease oxcarbazepine use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate estimates by a factor of 3- to 10-fold. Estimates of the background incidence rate for these serious skin reactions in the general population range between 0.5 to 6 cases per million-person years. Therefore, if a patient develops a skin reaction while taking Oxtellar XR®, consider discontinuing Oxtellar XR® use and prescribing another AED. Association with HLA-B*1502 Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with Oxtellar XR® treatment.

Human Leukocyte Antigen (HLA) allele B*1502 increases the risk for developing SJS/TEN in patients treated with carbamazepine. The chemical structures of immediate-release oxcarbazepine and Oxtellar XR® are similar to that of carbamazepine. Available clinical evidence, and data from nonclinical studies showing a direct interaction between immediate-release oxcarbazepine and HLA-B*1502 protein, suggest that the HLA-B*1502 allele may also increase the risk for SJS/TEN with Oxtellar XR®.

The frequency of HLA-B*1502 allele ranges from 2 to 12% in Han Chinese populations, is about 8% in Thai populations, and above 15% in the Philippines and in some Malaysian populations. Allele frequencies up to about 2% and 6% have been reported in Korea and India, respectively.

The frequency of the HLA-B*1502 allele is negligible in people from European descent, several African populations, indigenous peoples of the Americas, Hispanic populations, and in Japanese (<1%).

Testing for the presence of the HLA-B*1502 allele should be considered in patients with ancestry in genetically at-risk populations, prior to initiating treatment with Oxtellar XR®. The use of Oxtellar XR® should be avoided in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Consideration should also be given to avoid the use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Screening is not generally recommended in patients from populations in which the prevalence of HLA-B*1502 is low, or in current Oxtellar XR® users, as the risk of SJS/TEN is largely confined to the first few months of therapy, regardless of HLA-B*1502 status.

The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dosage, compliance, concomitant medications, comorbidities, and the level of

dermatologic monitoring have not been well characterized.

Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including Oxtellar XR®, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Epilepsy: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 3.4. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 3.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.4.

Psychiatric: Placebo Patients with Events per 1000 Patients 5.7. Drug Patients with Events per 1000 patients 8.5. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.5. Risk Difference: Additional Drug Patients with Events per 1000 Patients 2.9.

Other: Placebo Patients with Events per 1000 Patients 1.0. Drug Patients with Events per 1000 patients 1.8. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.9. Risk Difference: Additional Drug Patients with Events per 1000 Patients 0.9. Total: Placebo Patients with Events per 1000 Patients 2.4. Drug Patients with Events per 1000 patients 4.3. Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients 1.8. Risk Difference: Additional Drug Patients with Events per 1000 Patients 1.9.

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing Oxtellar XR® or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during Oxtellar XR® treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Withdrawal of AEDs As with most AEDs, Oxtellar XR® should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/ Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has occurred with immediate-release oxcarbazepine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocaraditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. Oxtellar XR® should be discontinued if an alternative etiology for the signs and symptoms cannot be established.

Hematologic Reactions Rare reports of pancytopenia, agranulocytosis, and leukopenia have been seen in patients treated with immediate-release oxcarbazepine during post-marketing experience. Discontinuation of Oxtellar XR® should be considered if any evidence of these hematologic reactions develops.

Risk of Seizures in the Pregnant Patient Due to physiological changes during pregnancy, plasma concentrations of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (MHD), may gradually decrease throughout pregnancy. Monitor patients carefully during pregnancy and through the postpartum period because MHD concentrations may increase after delivery.

Risk of Seizure Aggravation Exacerbation of or new onset primary generalized seizures has been reported with immediate-release oxcarbazepine. The risk of aggravation of primary generalized seizures is seen especially in children but may also occur in adults. In case of seizure aggravation, Oxtellar XR® should be discontinued.

ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety data presented below are from 384 patients with partial-onset seizures who received Oxtellar XR® (366 adults and 18 pediatric patients) with concomitant AEDs. In addition, safety data presented below are from a total of 2288 patients with seizure disorders treated with immediate-release oxcarbazepine; 1832 were adults and 456 were pediatric patients.

Most Common Adverse Reactions Reported by Adult Patients Receiving Concomitant AEDs in Oxtellar XR® Clinical Studies Table 3 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with Oxtellar XR® or placebo and concomitant AEDs and that were numerically more common in the patients treated with any dosage of Oxtellar XR® than in patients receiving placebo.

The overall incidence of adverse reactions appeared to be dose related, particularly during the titration period. The most commonly observed (≥5%) adverse reactions seen in association with Oxtellar XR® and more frequent than in placebo-treated patients were: dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, and asthenia.

Table 3: Adverse Reaction Incidence in a Controlled Clinical Study of Oxtellar XR® with Concomitant AEDs in Adults* Oxtellar XR® 2400 mg/day (N=123); Oxtellar XR® 1200 mg/day (N=122).

Placebo (N=121). Any System/Any Term: 69%, 57%, 55%. Nervous System Disorders: Dizziness: 41%, 20%, 15%; Somnolence: 14%, 12% 9%; Headache: 15% 8%, 7%; Balance Disorder: 7%, 5% 5%; Tremor: 1%, 5%, 2%; Nystagmus: 3%, 3%, 1%; Ataxia 1%, 3%, 1%. Gastrointestinal Disorders: Vomiting: 15% 6%, 9%; Abdominal Pain Upper: 0%, 3% 1%; Dyspepsia: 0% 3% 1%; Gastritis: 0%, 3% 2%. Eye Disorders: Diplopia: 13%, 10% 4%; Vision Blurred: 1%, 4%, 3%; Visual Impairment: 1%, 3%, 0%.

General Disorders and Administration Site Conditions: Asthenia: 7% 3%, 1%; Fatigue: 3%, 6%, 1%; Gait Disturbance: 0%, 3%, 1%; Drug Intolerance: 2%, 0%, 0%. Infections and Infestations: Nasopharyngitis: 0% 3%, 0%; Sinusitis: 0%, 3%, 2%. *Reported by ≥2% of patients treated with Oxtellar XR® and numerically more frequent than in the placebo group.

Adverse Reactions Associated with Discontinuation of Oxtellar XR® Treatment: Approximately 23.3% of the 366 adult patients receiving Oxtellar XR® in clinical studies discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with discontinuation of Oxtellar XR® (reported by ≥2%) were: dizziness (9.8%), vomiting (5.3%), nausea (3.7%), diplopia (3.2%), and somnolence (2.4%).

Adjunctive Therapy with Oxtellar XR® in Pediatric Patients 6 to Less Than 17 Years of Age Previously Treated with Other AEDs In a pharmacokinetic study in 18 pediatric patients (including patients 6 to less than 17 years of age) with partial-onset seizures treated with different dosages of Oxtellar XR®, the observed adverse reactions seen in association with Oxtellar XR® were similar to those seen in adults.

Most Common Adverse Reactions in Immediate-Release Oxcarbazepine Controlled Clinical Studies Controlled Clinical Studies of Adjunctive Therapy with Immediate-Release Oxcarbazepine in Adults Previously Treated with Other AEDs: Table 4 lists adverse reactions that occurred in at least 2% of adult patients with epilepsy treated with immediate-release oxcarbazepine or placebo with concomitant AEDs and that were numerically more common in the patients treated with any dosage of immediate-release oxcarbazepine than in placebo. As immediate-release oxcarbazepine and Oxtellar XR® were not examined in the same trial, adverse event frequencies cannot be directly compared between the two formulations.

Table 4: Adverse Reaction Incidence in a Controlled Clinical Study of Immediate Release Oxcarbazepine with Concomitant AEDs in Adults* Immediate-Release Oxcarbazepine Dosage (mg/day): OXC 600 (N=163); OXC1200 (N=171); OXC2400 (N=126); Placebo (N=166). Body as a Whole: Fatigue: 15%, 12%, 15%, 7%; Asthenia: 6% 3%, 6%, 5%; Edema Legs: 2%, 1%, 2%, 1%; Weight Increase: 1%, 2%, 2%, 1%; Feeling Abnormal: 0%, 1%, 2%, 0%. Cardiovascular System: Hypotension: 0%, 1%, 2%, 0%.

Digestive System: Nausea: 15%, 25%, 29% 10%; Vomiting: 13%, 25%, 36%, 5%; Pain Abdominal: 10%, 13%, 11%, 5%; Diarrhea: 5%, 6%, 7%, 6%; Dyspepsia: 5%, 5%, 6%, 2%; Constipation: 2%, 2%, 6%, 4%; Gastritis: 2%, 1%,2%,1%. Metabolic and Nutritional Disorders: Hyponatremia: 3%, 1%, 2%,1%. Musculoskeletal System: Muscle Weakness: 1%, 2%, 2%, 0%; Sprains and Strains: 0%, 2%, 2%, 1%. Nervous System: Headache: 32%, 28% 26%, 23%; Dizziness: 36%, 32%, 49%, 13%; Somnolence: 20%, 28%, 36%, 12%; Ataxia: 9%, 17%, 31%, 5%; Nystagmus: 7% 20%, 26% 5%; Gait Abnormal: 5%, 10%, 17%, 1%; Insomnia: 4%, 2%, 3%, 1%; Tremor: 3% 8%, 16%, 5%; Nervousness: 2%, 4%, 2%, 1%; Agitation: 1%,1%, 2%, 1%; Coordination Abnormal: 1%, 3%, 2%, 1%; EEG Abnormal: 0%, 0%, 2%, 0%; Speech Disorder: 1%, 1%, 3%, 0%; Confusion: 1%, 1%, 2%, 1%; Cranial Injury NOS: 1%, 0%, 2% 1%; Dysmetria: 1%, 2%, 3%, 0%; Thinking Abnormal: 0%, 2%, 4%, 0%. Respiratory System: Rhinitis: 2%, 4%, 5%, 4%; Skin and Appendages: Acne: 1%, 2%, 2%, 0%; Special Senses: Diplopia: 14%, 30%, 40%, 5%; Vertigo: 6%, 12%, 15%, 2%; Vision Abnormal: 6%, 14%, 13%, 4%; Accommodation Abnormal: 0%, 0%, 2%, 0%. *Events in at least 2% of patients treated with 2400 mg/day of immediate-release oxcarbazepine and numerically more frequent than in the placebo group.

Other Reactions Observed in Association with the Administration of Immediate-Release Oxcarbazepine In the paragraphs that follow, the adverse reactions, other than those in the preceding tables or text, that occurred in a total of 565 children and 1574 adults exposed to immediate-release oxcarbazepine and that are reasonably likely to be related to drug use are presented. Events common in the population, events reflecting chronic illness and events likely to reflect concomitant illness are omitted particularly if minor.

They are listed in order of decreasing frequency. Because the reports cite reactions observed in open-label and uncontrolled trials, the role of immediate-release oxcarbazepine in their causation cannot be reliably determined.

Body as a Whole: fever, malaise, pain chest precordial, rigors, weight decrease.

Cardiovascular System: bradycardia, cardiac failure, cerebral hemorrhage, hypertension, hypotension postural, palpitation, syncope, tachycardia.

Digestive System: appetite increased, blood in stool, cholelithiasis, colitis, duodenal ulcer, dysphagia, enteritis, eructation, esophagitis, flatulence, gastric ulcer, gingival bleeding, gum hyperplasia, hematemesis, hemorrhage rectum, hemorrhoids, hiccup, mouth dry, pain biliary, pain right hypochondrium, retching, sialoadenitis, stomatitis, stomatitis ulcerative.

Hematologic and Lymphatic System: thrombocytopenia.

Laboratory Abnormality: gamma-GT increased, hyperglycemia, hypocalcemia, hypoglycemia, hypokalemia, liver enzymes elevated, serum transaminase increased.

Musculoskeletal System: hypertonia muscle.

Nervous System: aggressive reaction, amnesia, anguish, anxiety, apathy, aphasia, aura, convulsions aggravated, delirium, delusion, depressed level of consciousness, dysphonia, dystonia, emotional lability, euphoria,

extrapyramidal disorder, feeling drunk, hemiplegia, hyperkinesia, hyperreflexia, hypoesthesia, hypokinesia, hyporeflexia, hypotonia, hysteria, libido decreased, libido increased, manic reaction, migraine, muscle contractions involuntary, nervousness, neuralgia, oculogyric crisis, panic disorder, paralysis, paroniria, personality disorder, psychosis, ptosis, stupor, tetany.

Respiratory System: asthma, bronchitis, coughing, dyspnea, epistaxis, laryngismus, pleurisy.

Skin and Appendages: acne, alopecia, angioedema, bruising, dermatitis contact, eczema, facial rash, flushing, folliculitis, heat rash, hot flushes, photosensitivity reaction, pruritus genital, psoriasis, purpura, rash erythematous, rash maculopapular, vitiligo, urticaria.

Special Senses: accommodation abnormal, cataract, conjunctival hemorrhage, edema eye, hemianopia, mydriasis, otitis externa, photophobia, scotoma, taste perversion, tinnitus, xerophthalmia.

Urogenital and Reproductive System: dysuria, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, micturition frequency, pain renal, pain urinary tract, polyuria, priapism, renal calculus, urinary tract infection.

Other: Systemic lupus erythematosus.

Laboratory Tests Serum sodium levels below 125 mmol/L have been observed in patients treated with immediate-release oxcarbazepine. Experience from clinical trials with immediate-release oxcarbazepine indicates that serum sodium levels return toward normal when the dosage is reduced or discontinued, or when the patient was treated conservatively (e.g., fluid restriction).

Laboratory data from clinical trials suggest that immediate-release oxcarbazepine use was associated with decreases in T4, without changes in T3 or TSH. Postmarketing and Other Experience The following adverse reactions have been observed in named patient programs or post-marketing experience with immediate-release oxcarbazepine or Oxtellar XR®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia, and arthralgia Cardiovascular System: atrioventricular block Digestive System: pancreatitis and/or lipase and/or amylase increase Hematologic and Lymphatic Systems: aplastic anemia Immune System Disorders: anaphylaxis Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion (SIADH) Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, Acute Generalized Exanthematous Pustulosis (AGEP) Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineral density, osteoporosis and fractures in patients on long-term therapy with immediate-release oxcarbazepine.

DRUG INTERACTIONS Effect of Oxtellar XR on Other Drugs It is recommended that the plasma levels of phenytoin be monitored during the period of Oxtellar XR titration and dosage modification. A decrease in the dosage of phenytoin may be required.

Effect of Other Drugs on Oxtellar XR If Oxtellar XR and strong CYP3A4 inducers or UGT inducers (e.g., rifampin, carbamazepine, phenytoin, and phenobarbital) are administered concurrently, it is recommended that the plasma levels of MHD be monitored during the period of Oxtellar XR titration. Dosage adjustment of Oxtellar XR may be required after initiation, dosage modification, or discontinuation of such inducers.

Hormonal Contraceptives Concurrent use of immediate-release oxcarbazepine with hormonal contraceptives may render these contraceptives less effective. Studies with other oral or implant contraceptives have not been conducted.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Oxtellar XR, during pregnancy.

Encourage women who are taking Oxtellar XR during pregnancy to enroll in the North American Antiepileptic Drug (NAAED Pregnancy Registry) by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.

Risk Summary There are no adequate data on the developmental risks associated with the use of Oxtellar XR® in pregnant women; however, Oxtellar XR® is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts, and cardiac malformations such as ventricular septal defects). Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Clinical Considerations An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period.

Data Human Data Data from published registries have reported craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects in children with prenatal oxcarbazepine exposure.

Animal Data When pregnant rats were given oxcarbazepine (30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m2 basis).

Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥300 mg/kg were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects.

In a study in which pregnant rabbits were orally administered MHD (20,

100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m2 basis). This dose produced only minimal maternal toxicity.

In a study in which female rats were dosed orally with oxcarbazepine (25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (0.6 times the MRHD on a mg/m2 basis). Oral administration of MHD (25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m2 basis).

Lactation Risk Summary Oxcarbazepine and its active metabolite (MHD) are present in human milk after oxcarbazepine administration. The effects of oxcarbazepine and its active metabolite (MHD) on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Oxtellar XR and any potential adverse effects on the breastfed infant from Oxtellar XR or from the underlying maternal condition.

Females and Males of Reproductive Potential Contraception Use of Oxtellar XR with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with decreased plasma concentrations of these hormones and may result in a failure of the therapeutic effect of the oral contraceptive drug. Advise women of reproductive potential taking Oxtellar XR who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control.

Pediatric Use The safety and effectiveness of Oxtellar XR® in pediatric patients 6 years of age and older for the treatment of partial-onset seizures is supported by: 1) An adequate and well-controlled safety and efficacy study of Oxtellar XR® in adults that included pharmacokinetic sampling, 2) A pharmacokinetic study of Oxtellar XR® in pediatric patients, which included patients 6 to less than 17 years of age, 3) Safety and efficacy studies with the immediate-release formulation in adults and pediatric patients.

Oxtellar XR® is not approved for pediatric patients less than 6 years of age because the size of the tablets are inappropriate for younger children.

Geriatric Use Following administration of single (300 mg) and multiple (600 mg/day) doses of immediate-release oxcarbazepine to elderly volunteers (60-82 years of age), the maximum plasma concentrations and AUC values of MHD were 30%-60% higher than in younger volunteers (18-32 years of age). Comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. Consider starting at a lower dosage and lower titration. Close monitoring of sodium levels is required in elderly patients at risk for hyponatremia.

Renal Impairment There is a linear correlation between creatinine clearance and the renal clearance of MHD. The pharmacokinetics of Oxtellar XR® has not been evaluated in patients with renal impairment. In patients with severe renal impairment (creatinine clearance <30 mL/min) given immediate-release oxcarbazepine, the elimination half-life of MHD was prolonged with a corresponding two-fold increase in AUC. In these patients initiate Oxtellar XR® at a lower starting dosage and increase, if necessary, at a slower than usual rate until the desired clinical response is achieved.

In patients with end-stage renal disease on dialysis, it is recommended that immediate-release oxcarbazepine be used instead of Oxtellar XR®.

Hepatic Impairment The pharmacokinetics of oxcarbazepine and MHD has not been evaluated in severe hepatic impairment, and therefore is not recommended in these patients.

DRUG ABUSE AND DEPENDENCE Abuse The abuse potential of Oxtellar XR® has not been evaluated in human studies.

Oxtellar XR® is not habit forming, and is not expected to encourage abuse.

Dependence Intragastric injections of oxcarbazepine to four cynomolgus monkeys demonstrated no signs of physical dependence as measured by the desire to self-administer oxcarbazepine by lever pressing activity.

OVERDOSAGE Human Overdose Experience Isolated cases of overdose with immediate-release oxcarbazepine have been reported. The maximum dose taken was approximately 48,000 mg.

All patients recovered with symptomatic treatment. Nausea, vomiting, somnolence, aggression, agitation, hypotension, and tremor each occurred in more than one patient. Coma, confusional state, convulsion, dyscoordination, depressed level of consciousness, diplopia, dizziness, dyskinesia, dyspnea, QT prolongation, headache, miosis, nystagmus, overdose, decreased urine output, and blurred vision also occurred.

Treatment and Management There is no specific antidote for Oxtellar XR® overdose. Administer symptomatic and supportive treatment as appropriate. Options include removal of the drug by gastric lavage and/or inactivation by administering activated charcoal.

CLINICAL PHARMACOLOGY Patients with Renal or Hepatic Impairment The effects of renal or hepatic impairment have not been studied for Oxtellar XR®.

Based on investigations with immediate-release oxcarbazepine, there is a linear correlation between creatinine clearance and the renal clearance of MHD. When immediate-release oxcarbazepine is administered as a single 300 mg dose in renally-impaired patients (creatinine clearance <30 mL/min), the elimination half-life of MHD is prolonged to 19 hours, with a two-fold increase in AUC. Dosage adjustment is recommended in these patients.

The pharmacokinetics and metabolism of immediate-release oxcarbazepine and MHD were evaluated in healthy volunteers and hepatically impaired subjects after a single 900 mg oral dose. Mild-to-moderate hepatic impairment did not affect the pharmacokinetics of immediate-release oxcarbazepine and MHD. The pharmacokinetics of oxcarbazepine and MHD have not been evaluated in severe hepatic impairment, and therefore it is not recommended in these patients.

Pregnant Women Due to physiological changes during pregnancy, MHD plasma levels may gradually decrease throughout pregnancy.

Drug Interaction Studies

In Vitro: Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. Results demonstrate that oxcarbazepine and its pharmacologically active 10-monohydroxy metabolite (MHD) have little or no capacity to function as inhibitors for most of the human cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9, and CYP4A11) with the exception of CYP2C19 and CYP3A4/5.

Although inhibition of CYP3A4/5 by oxcarbazepine and MHD did occur at high concentrations, it is not likely to be of clinical significance. The inhibition of CYP2C19 by oxcarbazepine and MHD, is clinically relevant.

In vitro, the UDP-glucuronyl transferase level was increased, indicating induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine were observed. As MHD, the predominant plasma substrate, is only a weak inducer of UDP-glucuronyl transferase, it is unlikely to have an effect on drugs that are mainly eliminated by conjugation through UDP-glucuronyl transferase (e.g., valproic acid, lamotrigine).

In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine calcium antagonists, oral contraceptives and cyclosporine resulting in a lower plasma concentration of these drugs.

Several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. No autoinduction has been observed with immediate-release oxcarbazepine.

As binding of MHD to plasma proteins is low (40%), clinically significant interactions with other drugs through competition for protein binding sites are unlikely.

In Vivo: Other Antiepileptic Drugs Potential interactions between immediate-release oxcarbazepine and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table 5.

Table 5: AED Drug Interactions with Immediate-Release (IR) Oxcarbazepine AED Coadministered (daily dosage); IR-Oxcarbazepine (daily dosage); Influence of IR-Oxcarbazepine on AED Concentration Mean Change (90% Confidence Interval); Influence of AED on MHD Concentration (Mean Change, 90% Confidence Interval). Carbamazepine (400-2000 mg): 900 mg, nc1, 40 % decrease [Cl: 17% decrease, 57% decrease]; Phenobarbital (100-150 mg): 600-1800 mg, 14% increase [Cl: 2% increase, 24% increase]; 25% decrease [Cl: 12% decrease, 51% decrease]. Phenytoin (250-500 mg): 600-1800 >1200-2400, nc1,2 up to 40% increase3 [Cl: 12% increase, 60% increase], 30% decrease [Cl: 3% decrease, 48% decrease]. Valproic Acid (400-2800 mg): 600-1800, nc1, 18% decrease [Cl: 13% decrease, 40% decrease]. Lamotrigine (200 mg): 1200, nc1, nc1.

1 nc denotes a mean change of less than 10%; 2Pediatrics; 3 Mean increase in adults at high doses of immediate-release oxcarbazepine Hormonal Contraceptives Coadministration of immediate-release oxcarbazepine with an oral contraceptive has been shown to influence the plasma concentrations of two components of hormonal contraceptives, ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI: 38-52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another study.

Other Drug Interactions Calcium Antagonists: After repeated coadministration of immediate-release oxcarbazepine, the AUC of felodipine was lowered by 28% [90% CI: 20-33]. Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels of MHD after coadministration with immediate-release oxcarbazepine.

Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD after coadministration with immediate-release oxcarbazepine. Results with warfarin show no evidence of interaction with either single or repeated doses of immediate-release oxcarbazepine.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In two-year carcinogenicity studies, oxcarbazepine was administered in the diet at doses of up to 100 mg/kg/day to mice and by gavage at doses of up to 250 mg/kg/day to rats, and the pharmacologically active 10-hydroxy metabolite (MHD) was administered orally at doses of up to 600 mg/kg/day to rats. In mice, a dose-related increase in the incidence of hepatocellular adenomas was observed at oxcarbazepine doses ≥70 mg/kg/day or approximately 0.1 times the maximum recommended human dose (MRHD) on a mg/m2 basis. In rats, the incidence of hepatocellular carcinomas was increased in females treated with oxcarbazepine at doses ≥25 mg/kg/day (0.1 times the MRHD on a mg/m2 basis), and incidences of hepatocellular adenomas and/or carcinomas were increased in males and females treated with MHD at doses of 600 mg/kg/day (2.4 times the MRHD on a mg/m2 basis) and ≥250 mg/kg/day (equivalent to the MRHD on a mg/m2 basis), respectively. There was an increase in the incidence of benign testicular interstitial cell tumors in rats at 250 mg oxcarbazepine/kg/day and at ≥250 mg MHD/kg/day, and an increase in the incidence of granular cell tumors in the cervix and vagina in rats at 600 mg MHD/kg/day.

Mutagenesis Oxcarbazepine increased mutation frequencies in the Ames test in vitro in the absence of metabolic activation in one of five bacterial strains. Both oxcarbazepine and MHD produced increases in chromosomal aberrations and polyploidy in the Chinese hamster ovary assay in vitro in the absence of metabolic activation. MHD was negative in the Ames test, and no mutagenic or clastogenic activity was found with either oxcarbazepine or MHD in V79 Chinese hamster cells in vitro. Oxcarbazepine and MHD were both negative for clastogenic or aneugenic effects (micronucleus formation) in an in vivo rat bone marrow assay.

Impairment of Fertility In a fertility study in which rats were administered MHD (50, 150, or 450 mg/kg) orally prior to and during mating and early gestation, estrous cyclicity was disrupted and numbers of corpora lutea, implantations, and live embryos were reduced in females receiving the highest dose (approximately two times the MRHD on a mg/m2 basis).

RA-OXT-BS-PV2

Emerging Science Abstracts to be Presented Today Continued from cover

Clinical Trials Plenary Session 9:15 a.m.–11:30 a.m., Terrace Ballroom A Phase 3 Study of Isradipine as a Disease Modifying Agent in Patients with Early Parkinson’s Disease (STEADY-PD III): Final Study Results Tanya Simuni, MD, on behalf of the Parkinson Study Group, Chicago, IL

Emerging Science Session 11:30 a.m.–6:30 p.m., Poster Hall Alternate Viewing Stage Data Blitz Presentations – 11:45 a.m.–12:45 p.m.

Poster Standby – 5:30 p.m.–6:30 p.m.

P3.6-071 Efficacy and Safety of PXT3003 in Patients with Charcot-Marie-Tooth Type 1A (CMT1A): Results of PLEO-CMT, an International Pivotal Phase 3 Trial Florian Thomas, MD, MA, PhD, FAAN, Hackensack, NJ P3.6-072 Serum Linc LNMAT1 Correlated with Phosphorylated α-Synuclein as Serum Biomarkers of Parkinson’s Disease: A Cross-Sectional Study Jing Zou, MD, PhD, MBBS, Guangzhou, Guangdong, China P3.6-073 Development of an AAV-based MicroRNA Gene Therapy for Treating Spinocerebellar Ataxia Type 3 Melvin Evers, Amsterdam, The Netherlands P3.6-074 STARS: Results from a Safety and Efficacy Study of OV101 (gaboxadol) in Adults and Adolescents with Angelman Syndrome Lynne Bird, San Diego, CA P3.6-075 Efficacy, Safety, and Tolerability of Rimegepant 75 mg Orally Dissolving Tablet for the Acute Treatment of Migraine: Results from a Phase 3, Double-Blind, Randomized, PlaceboControlled Trial, Study 303 Richard Lipton, MD, FAAN, Bronx, NY

P3.6-076 Cannabidiol (CBD; 10 and 20mg/kg/day) Significantly Reduces Convulsive Seizure Frequency in Children and Adolescents with Dravet Syndrome (DS): Results of a Doseranging, Multi-center, Randomized, Double-blind, Placebocontrolled Trial (GWPCARE2) Ian Miller, MD, Miami, FL P3.6-077 Safety, PK, PD, and Exploratory Efficacy in Single and Multiple Dose Study of a SOD1 Antisense Oligonucleotide (BIIB067) Administered to Participants with ALS Timothy M. Miller, MD, PhD P3.6-078 Zilucoplan, a Subcutaneously Self-Administered Peptide Inhibitor of Complement Component 5 (C5), for the Treatment of Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial and Open-Label LongTerm Extension James F. Howard, Jr., MD, FAAN P3.6-079 Efficacy and Safety of Eculizumab in Aquaporin-4 Antibody Positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD): A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Trial (PREVENT) Sean J. Pittock, MD P3.6-080 Kelch-like Protein 11 Autoantibodies Are a Novel Biomarker of Testicular Cancer-associated Paraneoplastic Encephalitis Divyanshu Dubey, MD P3.6-081 Modulation of CSF Caspase-3 in MSC-NTF Cells (NUROWN) in a Phase 2 ALS Study: Correlations with CSF Biomarkers and Clinical Response Ralph Z. Kern, MD 

DISCOVER EMERGING SCIENCE IN NEUROLOGY FROM GENENTECH Sunday, May 5th 12:15 pm and 3:15 pm

Tuesday, May 7th 12:00 pm | 1:00 pm | 2:00 pm | 3:00 pm

Genentech Pipeline Presentation

Neuromyelitis Optica Spectrum Disorder Presentation

Dr Susan Begelman, MD, FACC

Dr Adil Javed, MD, PhD

Vice President, Spectrum Medical Unit | US Medical Affairs | Genentech Inc. San Francisco, California

Associate Professor of Neurology The University of Chicago Chicago, Illinois

Monday, May 6th 12:30 pm and 2:30 pm

Wednesday, May 8th 12:00 pm | 1:00 pm | 2:00 pm | 3:00 pm

Spinal Muscular Atrophy Presentation Dr Claudia A. Chiriboga, MD, MPH

Multiple Sclerosis Presentation

Professor of Neurology and Pediatrics Division of Pediatric Neurology Columbia University Medical Center New York, New York

Dr Mark Cascione, MD Tampa Neurology Associates South Tampa Multiple Sclerosis Center Tampa, Florida

Monday, May 6th 11:30 am and 3:30 pm Huntington’s Disease Presentation Dr Victor Sung, MD Associate Professor, UAB Department of Neurology, Division of Movement Disorders Director, UAB/HDSA Huntington’s Disease Center of Excellence Birmingham, Alabama

Come to booth 2329 to learn about Genentech Neurology or visit us at roche.com/neuroscience

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