Issuu

Vol. 16, No. 3 • WINTER 2018

A MAGAZINE OF THE ALPHA-1 FOUNDATION

ALPHA- -TO-ONE Practical advice, personal experiences and

pertinent news for people touched by ALPHA-1

New leadership at the Foundation PAGE 4

MZ carrier state in Alpha-1

PAGE 12

A mother to the rescue

PAGE 28

“The job is not done, yet”

PAGE 24

LETTER FROM THE FOUNDATION LEADERSHIP

Focus on

A1F

nclusive and innovative have always been key words for the Alpha-1 Foundation since our inception under the leadership of John W. Walsh. The Foundation is constantly on the move to strengthen our community, support cutting-edge science, and reach our goal and core of our mission: to find a cure for Alpha-1 Antitrypsin Deficiency (Alpha-1).

The scientific programs, conferences and workshops covered in this issue exemplify the high-level of engagement the Foundation holds with key opinion leaders in the field. These meetings result in publications, recommendations and new ideas to approach Alpha-1 research. Recognition of donors at our donor dinner and events, such as the Escape to the Cape, give us an opportunity to bring our community together. The Foundation’s connection between patients, caregivers, scientific and medical professionals, industry and government, is the axis of our successful transition into the future. We always strive to identify improved ways to serve those affected by Alpha-1 and enhance our research portfolio. Change is sometimes necessary and essential to launch into a new era: more modern, efficient and effective. But one thing is constant, the commitment of our long-term staff, the dedication of our constituencies, and the resources needed to fuel research. As you read this issue, which coincides with our Year-End Appeal, we ask you to join us as we move into the future and contribute to our research fund so a cure for Alpha-1 is rapidly a reality. Through your support, we will make innovative strides and a defined impact on the future of Alpha-1. Together, as a collaborative community, we will move the Foundation’s mission forward! Happy holidays!

ALPHA- -TO-ONE Practical advice, personal experiences and pertinent news for people touched by Alpha-1, their families and friends VOL. 16, NO. 3 (Winter 2018) Published by the Alpha-1 Foundation 3300 Ponce de Leon Blvd., Coral Gables, FL 33134 (877) 2 CURE A1 (228-7321) www.alpha1.org Alpha-1 Foundation Board of Directors Executive Committee Jeanine D’Armiento, MD, PhD, Chair James Quill*, Vice-Chair & Treasurer Elizabeth Johnson*, Secretary Martin R. Zamora, MD, Scientific Advisor Gordon Cadwgan, PhD*, Immediate Past Chair Members Virginia Clark, MD Kenneth Irvine + Peggy Iverson* Jennifer Jopp* Ann Knebel, PhD, RN Noel G. McElvaney, MD, Mch, BAO, FRCPI, FRCPC James K. Stoller, MD, MS (Org. Dev.) Fred Walsh* Frank Willersinn, MD* Alpha-1 Foundation Executive Staff Miriam O’Day, Interim CEO Mark B. Delvaux, Vice President and CFO Adam Wanner, MD, Scientific Director Robert A. Sandhaus, MD, PhD, FCCP, Clinical Director Alpha-1-to-ONE Editorial Board Jen Childress +; William J. Martin II, MD; Jean-Marc Quach; Robert A. Sandhaus, MD, PhD, FCCP; Bruce C. Trapnell, MD Editor-in-Chief Miriam O’Day Executive Editor Karen Erickson Managing Editor Bernardo A. Pisani Editorial Manager Alejandro E. Hernandez Padilla Contributing Editors Alexis E Artiles; Barbee Bennington; Adriana DeArce; Steven Hays, MD; Cathey Horsak; Richard Lovrich; Angela McBride; Randel Plant; Marelis Requejado; Linda Rodriguez; Eryn Varano ALPHA-1-TO-ONE is published by the Alpha-1 Foundation with support from its advertisers. No part may be reproduced in any form by any means without prior written permission of the Alpha-1 Foundation. The contents are not intended to provide medical advice, which should be obtained directly from a physician. The Foundation is not responsible for the accuracy of information expressed in advertisements in this publication. Advertising: For advertising inquiries, please contact Angela McBride, Director of Corporate Relations at (877) 228-7321 ext. 233, or amcbride@alpha1.org. Letters to the Editor: Please send letters to the editor to aehernandez@alpha1.org. Letters may be edited for clarity and length.

1 ALPHA-1 FOUNDATION

The Alpha-1 Foundation is committed to finding a cure for Alpha-1 Antitrypsin Deficiency and to improving the lives of people affected by Alpha-1 worldwide. *Diagnosed with Alpha-1 Antitrypsin Deficiency + Diagnosed Family Member

Jeanine D’Armiento, MD, PhD Chair, Board of Directors

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Inside

Vol. 16, No. 3 • WINTER 2018

A MAGAZINE OF THE ALPHA-1 FOUNDATION

ALPHA- -TO-ONE

Features

SPOTLIGHT Jeanine D’Armiento: a new leader New Board Chair, Jeanine D’Armiento, MD, PhD .............................................................................page 4

FRONTIERS Investigators’ meeting How do we know what our research grantees have accomplished ...............................................................page 6 The Clinical Resource Centers (CRC) Forum Every other year, CRCs are invited to catch up on the latest information ...................................................page 7 MZ Carrier State in Alpha-1 Antitrypsin Deficiency A summary of clinical manifestations of the MZ carrier state ..................................................................page 12 17th Gordon Snider Critical Issues Workshop The workshop featured the NIH and the NHLBI COPD National Action Plan ......................................page 19 Alpha-1 research studies enrolling The latest Alpha-1 studies enrolling volunteers through the Alpha-1 Research Registry ..............................page 32 ALPHA LIFE Alpha-1 Foundation Donor Recognition Dinner The ongoing research would not be possible without the generosity of our major donors ..................................page 14 Steven Shurtz: waiting for the next phase A close interview of an Alpha by an Alpha. Richard Lovrich visits long-time friend Steven Shurtz ................page 26 ALPHA-1 KIDS A mother to the rescue When a mother does what has to be done to save her child ........................................................................page 28

IN YOUR INTEREST Escape to the Cape: Team Alpha-1 made it happen, again This year, 100 riders and 82 volunteers helped raise $100,000 for Alpha-1 research ...............................page 11 Globally connected by a common purpose The 7th Alpha-1 Global Patient Congress in 2019 in Croatia ..............................................................page 21 ALPHA-1 COMMUNITY Camaraderie and support in the Northeast Support Group Leaders keep up the good work ......................................................................................page 8 Bob Nichols: serving others for more than three decades A retired professional paramedic/firefighter and now AlphaNet Coordinator ..............................................page 17 Ken Richmond: “The job is not done, yet” Advocacy plays an important role in our community ...............................................................................page 24 ASK THE ALPHA DOC Steven Hays, MD, as our guest physician in this issue ............................................................................page 22

CALENDAR 2018 - 2019 Support group meetings, webinars, events and education days in Alpha-1 ...................................................page 31 Cover photo by Richard Lovrich

fb.com/alpha1foundation www.alpha1.org

@AlphaFriend

@alpha1foundation

@Alpha-1FDN 3

SPOTLIGHT

Jeanine D’Armiento:

New leadership at the Foundation J

eanine M. D’Armiento, MD, PhD, is the new chair of the Board of Directors at the Alpha-1 Foundation. D’Armiento previously served on the Executive Committee of the Foundation and now embarks on a new chapter as the gavel is passed from Gordon E. Cadwgan, PhD, who is now immediate past chair.

She has had a soft spot for the Foundation since very early in her career, when she attended research events sponsored by the Foundation, and met co-founder John W. Walsh and Robert A. Sandhaus, MD, PhD, clinical director of the Foundation and

D’Armiento wears many hats in her day-to-day work at Columbia University in New York City. She is a professor of medicine, where she directs the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics, as well as the Center for Lymphangioleiomyomatosis (LAM) and Rare Lung Disease. Her clinical center serves as a tertiary referral center for the Northeast region, and cares for patients with LAM and Alpha-1 Antitrypsin Deficiency (Alpha-1). She is a leader who brings a deep understanding of the science and the clinical needs of Alpha-1 patients. Her volunteer commitment to the Foundation is a gift to our constituency. D’Armiento’s early career was focused on emphysema and chronic obstructive pulmonary disease (COPD). In graduate school, she began investigating an enzyme called MMP-1, part of a whole family called “metalloproteases” that destroy lung tissue. “In college I had worked with some premier biochemists who had isolated that family of proteases,” she says.

D’Armiento with staff at her laboratory at Columbia University Medical Center (CUMC)

1.877.2.CURE.A1 (228.7321)

medical director of AlphaNet: “very early in my career, while doing my PhD, I was looking at lung injury and COPD. At the time, Alpha-1 meetings were the place to be because everybody who was somebody in COPD research would be there, so, as a young investigator I wanted to be there, too,” she explains. “My first encounter with Alpha-1 was at an American Thoracic Society (ATS) meeting. John (Walsh) and Sandy (Sandhaus) were very warm and very encouraging, they were a big part of the connection for me. The networking I was able to do at those meetings was critical as a young investigator trying to get into the research field,” she adds.

John W. Walsh and Jeanine D’Armiento, MD, PhD

In fact, D’Armiento’s first grant for lung research came from the Foundation in 2004, when she was awarded a postdoctoral research fellowship to study cigarette smoke and cell signaling in emphysema. MMP-1 was a part of that study. “Most of my research in rare diseases is founded on that work,” she says. “The Foundation grant helped me to achieve National Institutes of Health (NIH) funding for lung disease, just what I wanted to do,” she says. As a young researcher, she attended many Foundation-sponsored events at the ATS annual meeting and elsewhere, and “the interaction between the Board, researchers and clinicians, and patients was exceptional. Patients lead the Foundation with great respect for healthcare professionals, and vice versa.” D’Armiento accepted an invitation from John Walsh and Marcia Ritchie, previous vice president and chief operating officer of the Foundation to join the Board in 2011, and has been a member ever since. “They were both on the phone and said that they would like me to join the Board. I was a little in shock because I did not expect that, but at the same time I was so honored,” she says. www.alpha1.org

Her vision as Chair of the Board As the new chair of the Board of Directors, D’Armiento’s vision focuses on bringing the patient support and research networks closer together for a cohesive and effective approach that will ultimately benefit both. “I believe that the key to this organization is the link between patient support and research, and the best way to approach this is to bring together some of the programs that we have, for example, get our Clinical Resource Centers (CRCs) really connected with the patients, but also connected with research, so we have a seamless approach to our population,” she explains. “I think it’s important to strengthen both sides: research and patient support, and the best way to do that is through our really high-quality clinical centers. I think that is something I see moving forward,” she adds. Today, her broad research work includes Alpha-1 and ranges from COPD to asthma to smoke injury. In March, she was honored by the Celtic Connection committee with the Shillelagh Award for her work in Alpha-1 research and her active role as a board member. “I consider it a great privilege to chair the Foundation’s Board of Directors and look forward to doing amazing work as we progress together toward a cure for Alpha-1,” she finished. To learn more about Jeanine D’Armiento, MD, PhD, and her new role as the chair of the Board, please visit our website at www.alpha1.org. 1 ALPHA-1 FOUNDATION 5

FRONTIERS 6

Investigators’ Meeting:

How do we know what our research grantees have accomplished?

he Alpha-1 Foundation has been sponsoring research grants for nearly 20 years. To date, it has invested more than $71 million to support alpha-1 antitrypsin research (AAT) and related programs at 112 institutions worldwide. All research applications are peer-reviewed for scientific merit before they are funded. However, the outcome of the proposed research and hence its impact on our understanding of alpha-1 liver and lung disease cannot be predicted with certainty. For example, an investigator may propose to find out why the mutant AAT protein is not secreted from the liver and aim to develop a specific treatment for the defect. Their research may clarify the reason for the abnormal secretion, but the suggested treatment may fail. The study must be judged partially successful because it identified the defective mechanism but not a treatment for it. This information is brought to the attention of the research community at large because another investigator may target the secretion defect with another solution that works. How does the result of the research get disseminated? There are two major ways to accomplish this. One is the publication of the research findings in the scientific literature where it is easily accessible by other researchers. The other is to present the data at a scientific meeting. Therefore, the Foundation withholds the last payment on an active research grant until evidence is submitted that the work has been published in a journal or submitted as an abstract to a national or international scientific meeting. In addition, the Foundation created the Biennial Investigators’ Meeting on alpha-1 antitrypsin for investigators who have been supported by Foundation grants during the two years preceding the meeting. The fourth conference of this sort took place in Miami, Florida on Sept. 7, 2018. The four sessions

Investigators’ Meeting, September 7, 2018 in Miami, Florida

of the meeting addressed mechanisms of lung disease, mechanisms of liver disease, observational studies in patients with Alpha-1 Antitrypsin Deficiency (Alpha-1), and novel therapies. There were 23 individual presentations followed by productive discussions. While all research reports were fascinating and contributed to a better understanding of Alpha-1 related lung and liver disease, a few stood out in their impact on advancing research. Chris Mueller, MD, from the University of Massachusetts (UMass), has developed an ATT knock-out mouse model that mimics many features of COPD in patients with Alpha-1 and will certainly help future drug development for the condition. Joseph Kaserman, MD, from Boston University (BU), explained his novel and innovative research to reprogram human cells to mimic native liver cells from individuals with and without Alpha-1 that can be used to test new drugs in vitro. Monica Goldklang, MD, from Columbia University presented a unique imaging technique that can identify a mechanism of lung cell loss, a feature of COPD. This mechanism is “druggable” and may be valuable in future interventional studies. Other presentations addressed new ways to make recombinant alpha-1 for therapy, new approaches to promote proper folding of misfolded alpha-1 and several inflammatory processes unique to alpha-1 and potentially targetable with new drugs. In addition there was a presentation on the medical costs of Alpha-1-related COPD in the U.S. showing that when adjusting for augmentation therapy, the health cost of COPD in Alphas is twice that for common COPD. The objective of the meeting was to create a forum for scientific discourse among investigators interested in Alpha-1 and supported by the Foundation. This goal was clearly met and we look forward to the next Investigators’ Meeting in 2020. 1 ALPHA-1 FOUNDATION

1.877.2.CURE.A1 (228.7321)

he Clinical Resource Centers (CRCs) of the Alpha-1 Foundation are the more than 80 geographically dispersed medical practices with experience in identifying and treating individuals with Alpha-1 Antitrypsin Deficiency (Alpha-1). Many of the CRCs also conduct basic and clinical research into Alpha-1. Every other year, representatives from each of our CRCs are invited to get caught up on the latest information about Alpha-1 and to share their advice and experience with others. The most recent CRC Forum was held in Miami, Florida, on September 8th. Forty CRCs attended the Forum and the networking reception that accompanied it. The reception included industry partners and Foundation board members. During the day long Forum, CRC physicians and staff were introduced to the Foundation’s interim CEO, Miriam O’Day who welcomed all to Miami. Jim Donohue, MD, the chair of the working group that oversees the CRC program, introduced the agenda for the meeting and the goals of the CRC program. Adam Wanner, MD, the Foundation’s scientific director, presented the Foundation’s latest iteration of the research agenda, a living document that is revised on a regular basis to reflect the most important and interesting areas of current Alpha-1 research. Jeanine D’Armiento, MD, PhD, the Foundation’s board chair, reviewed an exciting research project that the Foundation is considering, which helps identify the risks of lung and liver disease in those with an MZ genotype for Alpha-1, and whether specific therapy might be beneficial in this group. It is anticipated that, as this project moves forward, it will eventually be large enough to include all the CRC sites as investigators. Jeffrey Teckman, MD, presented the latest information on liver disease in Alpha-1 and advances in management of this condition. The morning session continued with talks by Robert A. Sandhaus, MD, PhD, FCCP, Karen Fraser,

and Kristen Holm, PhD, MPH, reviewing the AlphaNet health management and REACH programs as well as some of the information learned through the many questionnaires that AlphaNet participants complete each year. Just before lunch, Roberto Balderas, the Foundation’s grassroots advocacy manager, reviewed his program with the CRC participants. Three augmentation therapy industry partners gave short updates, as well. After lunch, Charlie Strange, MD, talked about challenges associated with recruiting Alphas to participate in clinical trials and ways to improve the clinical trial experience for participants. This was followed by Kenneth Goodman, PhD, FACMI, the director of bioethics at the University of Miami School of Medicine, talking about ethical issues in clinical trial recruitment. The day ended with Sandhaus moderating an exchange of information among the CRCs about challenges they’ve identified in Alpha-1 management and ways they’ve found to solve them. In summary, this was the most successful CRC Forum held by the Foundation based on the number of sites who attended and the quality of the discussion among the sites. We will be following up with all the CRCs based on the information shared during the sessions and look forward to shared educational and study opportunities utilizing the combined resources of our nationwide CRC network. All this is aimed at continuously improving the care of those affected by Alpha-1.

FRONTIERS

Clinical Resource Center Forum held in Miami

Attendees at the 2018 Clinical Resource Center Forum in Miami, Florida

Several action items were identified that the Foundation was charged with addressing. These included the following: • Inform CRC directors about currently enrolling studies and invitations to participate in studies sent to patients in their geographic areas. • Provide example letter templates to all CRCs that can be used for a variety of insurance issues and appeals on behalf of Alpha-1 patients. • Update the Foundation website to include copies of the new physician’s pocket guide and promotional flyers. 1 ALPHA-1 FOUNDATION

www.alpha1.org

ALPHA-1 COMMUNITY

Camaraderie and support in the Northeast Alpha Mainers support group Portland, ME Brian Pelletier was diagnosed with Alpha-1 Antitrypsin Deficiency (Alpha-1) in 2003. He created the Alpha Mainers support group in 2008, but shortly after he moved to Boston, Massachusetts, because he was listed for a lung transplant. Pelletier did not give up the group; when he recovered from surgery, he went right back and identified Valarie Hale as a co-leader. To their amazement, they quickly found themselves covering the whole state of Maine, having meetings from Portland to Caribou. The Alpha Mainers meet from four to six times per year and what Pelletier finds most satisfying is making sure Alphas do not go down the same path as he did: “it took me a long while to get diagnosed. I got tested for Alpha-1 but my doctor read the test wrong, which was an issue, this made me get more proactive,” he says. Pelletier also makes sure that Alphas are aware of the programs and options available to them and get the support they need. “When you get diagnosed you feel alone, so being able to talk to another Alpha is the best. The big thing is the camaraderie.”

CT Nutmeggers support group Colchester, CT Faithe Petty co-leads the CT Nutmeggers with Christopher Town, PhD. For Petty, the most satisfying aspect of being a support group leader is seeing everybody come together and support each other, “the camaraderie in the group is very rewarding. As a caregiver, being part of that and seeing other caregivers come to our meetings with Alphas, is such an amazing experience,” she says. The opportunity of meeting together to talk between Alphas, caregivers, family members, 8

and seeing how they can all rely on one-another, is very rewarding for Petty. The CT Nutmeggers meet quarterly.

Capital Region of NY Alpha-1 support group Albany, NY Carolyn Koch recently became the support group leader of the Capital Region of New York. Richard Lovrich founded the group in 2016. For Koch, the most important thing is to provide the group members with what they need, whether it is information or someone to talk to: “just the community and knowing that you are not alone, and to be able to share your feelings and what you are going through is the most important thing. Also, I want to be able to bring more people into the group and help more Alphas,” she says. The group used to meet at the Proctors Performing Arts Center, in Schenectady, but it recently moved to the Pulmonary Rehabilitation Center at St. Peter’s Hospital, in Albany. The new location provides easier access to Alphas and medical assistance, if needed. The group had meetings in September and October, and Koch is currently planning upcoming meetings for 2019. We need support group leaders in: Alaska, Delaware, Hawaii, Mississippi, Montana, New Hampshire, New Jersey, New Mexico, North Carolina, North Dakota, Rhode Island and Vermont. Please contact Barbee Bennington, support group and program coordinator, at (855) 351-6610 or (480) 285-6177, or via email at bbennington@alpha1.org. 1 ALPHA-1 FOUNDATION

1.877.2.CURE.A1 (228.7321)

NOW AVAILABLE READY-TO-INFUSE

PROLASTIN C LIQUID

The #1 prescribed alpha-1 therapy for over 25 years is now available in a new, ready-to-infuse liquid formulation. • 15-minute infusion time remains the same • Proven to effectively raise the alpha1-antitrypsin protein levels in patients with alpha1-antitrypsin deficiency, also known as alpha-1

• With PROLASTIN-C LIQUID, all your PROLASTIN DIRECT® program benefits and services remain the same

• The PROLASTIN DIRECT program gives you the confidence that ongoing personalized support is there for you when needed

Steve M. and his wife, Ellen. Steve has been on therapy since 2007.

Visit our new website, www.prolastin.com/LIQUID, for more information and patient-friendly resources.

Important Safety Information PROLASTIN®-C LIQUID is an alpha1-proteinase inhibitor (human) (alpha1-PI) indicated for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of alpha1-PI (alpha1-antitrypsin deficiency).

Hypersensitivity reactions, including anaphylaxis, may occur. Monitor vital signs and observe the patient carefully throughout the infusion. If hypersensitivity symptoms occur, promptly stop PROLASTIN-C LIQUID infusion and begin appropriate therapy.

Limitations of Use • The effect of augmentation therapy with any alpha1PI, including PROLASTIN-C LIQUID, on pulmonary exacerbations and on the progression of emphysema in alpha1-PI deficiency has not been conclusively demonstrated in randomized, controlled clinical trials

Because PROLASTIN-C LIQUID is made from human plasma, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.

• Clinical data demonstrating the long-term effects of chronic augmentation or maintenance therapy with PROLASTIN-C LIQUID are not available

The most common adverse reactions during PROLASTIN-C LIQUID clinical trials in >5% of subjects were diarrhea and fatigue, each of which occurred in 2 subjects (6%).

• PROLASTIN-C LIQUID is not indicated as therapy for lung disease in patients in whom severe alpha1-PI deficiency has not been established PROLASTIN-C LIQUID is contraindicated in immunoglobulin A (IgA)-deficient patients with antibodies against IgA or patients with a history of anaphylaxis or other severe systemic reaction to alpha1-PI products.

Please see brief summary of the full Prescribing Information for PROLASTIN-C LIQUID on adjacent page. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

July 2018

BN/PRL/0618/0047(1)

PROLASTIN®-C LIQUID

Alpha1-Proteinase Inhibitor (Human) HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PROLASTIN®-C LIQUID safely and effectively. See full prescribing information for PROLASTIN-C LIQUID. PROLASTIN®-C LIQUID (Alpha 1-Proteinase Inhibitor [Human]) Solution for Intravenous Injection Initial U.S. Approval: 1987 ---------------INDICATIONS AND USAGE ------------PROLASTIN-C LIQUID is an Alpha1-Proteinase Inhibitor (Human) (Alpha1-PI) indicated for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of Alpha1-PI (alpha1-antitrypsin deficiency). Limitations of Use: • The effect of augmentation therapy with any Alpha1-PI, including PROLASTIN-C LIQUID, on pulmonary exacerbations and on the progression of emphysema in Alpha1-PI deficiency has not been conclusively demonstrated in randomized, controlled clinical trials. • Clinical data demonstrating the long-term effects of chronic augmentation or maintenance therapy with PROLASTIN-C LIQUID are not available. • PROLASTIN-C LIQUID is not indicated as therapy for lung disease in patients in whom severe Alpha1-PI deficiency has not been established. -----------DOSAGE AND ADMINISTRATION--------For intravenous use only. • Dose: 60 mg/kg body weight intravenously once per week. • Dose ranging studies using efficacy endpoints have not been performed with any Alpha1-PI product, including PROLASTIN-C LIQUID.

• Use a sterile 15 micron in-line filter when administering the product (not supplied). • Administration: 0.08 mL/kg/min as determined by patient response and comfort. ---------DOSAGE FORMS AND STRENGTHS------For injection: approximately 1,000 mg in a singleuse vial containing 20 mL of solution for injection. ------------------CONTRAINDICATIONS ---------------• Immunoglobulin A (IgA) deficient patients with antibodies against IgA. • History of anaphylaxis or other severe systemic reaction to Alpha1-PI. -----------WARNINGS AND PRECAUTIONS --------• Severe hypersensitivity and anaphylactic reactions may occur in IgA deficient patients with antibodies against IgA. Discontinue administration of the product and initiate appropriate emergency treatment if hypersensitivity reactions occur. • Because PROLASTIN-C LIQUID is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ------------------ADVERSE REACTIONS---------------The most common adverse reactions during PROLASTIN-C LIQUID clinical trials in > 5% of subjects were diarrhea and fatigue, each of which occurred in 2 subjects (6%). To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics Inc. at 1-800520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Grifols Therapeutics Inc. Research Triangle Park, NC 27709 USA U.S. License No. 1871

3045824-BS Revised: 9/2017

Team Alpha-1 made it happen, again

Written by Judith Vargas-Vila

very September, the scenic coast of Cape Cod, Massachusetts, is the perfect stage for the annual Escape to the Cape fundraising bike trek, a 165-mile bicycle ride from Plymouth to Provincetown. An unforgettable three-day weekend filled with fun and camaraderie. This year, 100 riders and 82 volunteers on Team Alpha-1 came together and helped raise $100,000 for Alpha-1 Antitrypsin Deficiency (Alpha-1) research and related programs, and this is how it happened:

Through the eyes of an Alpha... Paint this picture in your mind: Alpha-1 volunteers working together, making peanut butter, jelly and fluffernutter sandwiches, pitching and moving tents as riders pass towards Provincetown; and now add the views of little New England towns, sparkling water and sand dunes, wheeling seabirds and the fresh salt-breath of the Atlantic. You are there, at the Escape to the Cape. Take part and make a difference. There will be another Escape to the Cape next year. Come join us or take a local walk event to your town.

IN YOUR INTEREST

Escape to the Cape:

There was a crowd and “I have Alpha-1 creative chaos at every Antitrypsin Deficiency. bike rest stop, and I also have had we gathered at night a double lung to enjoy each other’s transplant. I was part company; the air was of this excitement. I filled with excitement had the satisfaction and goodwill. Hundreds of knowing I was on of generous people had the front line here, come together after a day not sitting in the of hard work pushing background always their bodies and bikes to receiving.” cover the miles scheduled and continued to ride the rest of the weekend to earn money for research into Alpha-1. One hundred bikers enrolled to ride for Alpha-1, many of them Alphas riding with an oxygen “Some have tank, or even new lungs, participated for joining riders of all many years. experience levels, all Some rode for a bringing funding for family member, research. Enthusiasm or a friend, or for and friendship, delight the many Alphas to be working together, that cannot find and eagerness to share experiences flooded the breath to ride the roads. themselves.” Team Alpha -1 included volunteers from pharmaceutical companies and riders from research labs that are searching for the cure, including the medical research team from Boston University. After three decades, there are new young teams of supporters forming to carry on the work and create memories. Some have participated for many years. Those who can’t ride were not left out. Some of us purple-shirted volunteers helped especially in cheering the riders. We could all shout “thank you!” as they crunched by on their cleats and jumped back onto their bikes. This successful event brings camaraderie, compassion and fundraising for a cure. Once you participate, you will Thank you to AlphaNet, be forever changed. 1 ALPHA-1 FOUNDATION CSL Behring, Dohmen Life Science Services, Grifols, and Shire for their amazing support.

www.alpha1.org

FRONTIERS

MZ Carrier State in Alpha-1 Antitrypsin Deficiency (Alpha-1)

n recent years, the Alpha-1 patient community has raised concerns about the potential for lung and/or liver disease in the MZ carrier state. To address this concern, the Alpha-1 Foundation hosted the 16th Gordon L. Snider Critical Issues Workshop on Nov. 13, 2017, in Bethesda, Maryland. The workshop, “MZ Carrier State in Alpha-1 Antitrypsin Deficiency,” featured two expert-led sessions: Carrier States in Rare Diseases and Observational and Mechanistic Studies in Alpha-1 Antitrypsin Deficiency. There were 70 attendees representing academia, the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and industry and voluntary healthcare organizations. The purpose of the workshop was to summarize what is currently known about the clinical manifestations and biology of the MZ carrier state and to develop an action plan to address the unanswered questions. The presentations were opened by Joshua Denny, MD, MS, who reported on a Vanderbilt-based database that links electronic medical records to a DNA repository to explore phenotype-genotype relationships. Based on the analysis of 250,000 samples, the data showed an elevated risk score for clinical disease in MZ carriers, suggesting that the MZ carrier state impacts one’s general health status. Noel McElvaney, MD, BCh, BAO, FRCPI, FRCPC, from the Royal College of Surgeons in Dublin, showed in a family-based longitudinal study that MZ carriers who smoke (but this is not the case for MZ non-smokers) have an accelerated decline in lung function over time. This important finding is strengthened by the National Heart

Lung and Blood Institute (NHLBI) sponsored COPDGene project as reported at the meeting by Marilyn Foreman, MD, MS, from Morehouse Medical School. She stated that MZ carriers may confer a chronic obstructive pulmonary disease (COPD) risk. Presentations then turned to liver disease in MZ or MS carriers. First, Pavel Strnad, MD, from the University of Aachen in Germany, presented the results of a study involving carriers of the MZ and MS genotypes and non-carriers. The investigators found that MZ carriers had significantly higher liver enzymes and evidence of liver cirrhosis than non-carriers. A possible mechanism for this observation was offered by David Lomas, MD, PhD, from the University of London, U.K. He reported that the MZ protein can form polymers by showing that a single copy of the Z allele is sufficient to form polymers within liver cells and may act as a co-factor in driving liver disease in MZ carriers. It was a highly informative conference that provided new information on lung and liver disease in MZ heterozygotes that identified gaps in our current understanding of the condition and pointed to future research needed. With the advent of direct-to-consumer genotyping platforms, the detection rate of MZ carriers is expected to rise, and with it the need to better serve that growing population. In this sense, the conference was timely and successful in pointing to future research that will clarify the health management for this population. The meeting proceedings have been formally published in greater detail in the Journal of Translational Research in Rare Diseases (Trans Sci Rare Dis 2018; 3: 105-120).

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A discussion to summarize what is currently known and what still needs to be investigated about lung and liver disease in the MZ carrier state took place. Based on the state of the science, as summarized at the meeting, the following conclusions were drawn and recommendations made:

A. Risk of lung and liver disease in individuals with the MZ genotype: • Those who smoke are at greater risk for COPD than smokers in the general population • Occupational and environmental exposures may also influence lung disease in smokers • Those who do not smoke are not at an increased risk for COPD • They are at increased risk for end-stage adult liver disease • Heavy alcohol use and Hepatitis C are likely to increase the risk of end-stage liver disease

B. What more would we like to know? • What is the magnitude of the risk for lung and liver disease in the MZ population? • Is there a difference in the clinical and pathological type of lung and liver disease between the MZ and ZZ genotypes? • Are there modifier genes that increase the risk of lung or liver disease in individuals with the MZ genotype? • What is the mechanism of lung and liver disease in MZ carriers? • Does Alpha-1 in MZ individuals with COPD influence the severity of disease exacerbations? • Does COPD in MZ carriers progress after smoking cessation? • Should we treat MZ carriers with COPD differently from MM COPD patients? • Does silencing the Z protein in the liver have beneficial effects on lung disease?

C. Potential research strategies: • Choosing specific biomarkers for observational and interventional clinical studies in MZ heterozygotes • Use large population-based studies taking advantage of existing databases to assess the risk of lung or liver disease in MZ heterozygotes • Determine the impact of the Z protein on cell-based and animal-based models of lung disease • Determine how to design a trial of MZ heterozygotes for augmentation therapy

www.alpha1.org

1 ALPHA-1 FOUNDATION

ALPHA LIFE

Alpha-1 Foundation

Donor Recognition Dinner

n Thursday, Sept. 6, 2018, Alpha-1 Foundation philanthropists, patients, physicians, investigators and industry partners joined together in Miami, Florida, at the biennial Alpha-1 Foundation Donor Recognition Dinner. The evening kicked off with a keynote speaker, Emer Reeves, PhD, from the Royal College of Surgeons, Ireland, who presented the latest findings on the Alpha-1 Antitrypsin Deficiency (Alpha-1) research she leads. Major Donors recognized at Donor Dinner The ongoing research and findings would not be possible without the generosity of our major donors, corporations and foundations that have supported our commitment to finding a cure for Alpha-1 and to improving the lives of those affected by Alpha-1 worldwide. The evening honored new members to the giving circles and thanked all major donors for their continued support. A new circle was created and named the Visionary Circle, and was presented to AlphaNet AlphaNet staff and Alpha-1 Foundation board members for donating over $50 million to the Alpha-1 Foundation. 1 ALPHA-1 FOUNDATION

1.877.2.CURE.A1 (228.7321)

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Important Safety Information Zemaira® is indicated to raise the plasma level of alpha1-proteinase inhibitor (A1-PI) in patients with A1-PI deficiency and related emphysema. The effect of this raised level on the frequency of pulmonary exacerbations and the progression of emphysema have not been established in clinical trials. In clinical studies, the following adverse reactions were reported in at least 5% of subjects receiving Zemaira: headache, sinusitis, upper respiratory infection, bronchitis, fatigue, increased cough, fever, injection-site bleeding, nasal symptoms, sore throat, and swelled blood vessels. Please see full Important Safety Information and brief summary of prescribing information for Zemaira on the following page.

Zemaira is manufactured and distributed by CSL Behring LLC. Zemaira® and CareZ® are registered trademarks of CSL Behring LLC. Zemaira® Signature SavingsSM and CSL Behring AssuranceSM are service marks of CSL Behring LLC. ©2017 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA www.CSLBehring-us.com www.Zemaira.com ZMR-0101-OCT17

Important Safety Information ZemairaÂŽ is indicated to raise the plasma level of alpha1-proteinase inhibitor (A1-PI) in patients with A1-PI deficiency and related emphysema. The effect of this raised level on the frequency of pulmonary exacerbations and the progression of emphysema have not been established in clinical trials. Zemaira may not be suitable for everyone; for example, people with known hypersensitivity to components used to make Zemaira, those with a history of anaphylaxis or severe systemic response to A1-PI products, and those with certain IgA deficiencies. If you think any of these may apply to you, ask your doctor. Early signs of hypersensitivity reactions to Zemaira include hives, rash, tightness of the chest, unusual breathing difficulty, wheezing, and feeling faint. Immediately discontinue use and consult with physician if such symptoms occur. In clinical studies, the following adverse reactions were reported in at least 5% of subjects receiving Zemaira: headache, sinusitis, upper respiratory infection, bronchitis, fatigue, increased cough, fever, injection-site bleeding, nasal symptoms, sore throat, and swelled blood vessels. Because Zemaira is made from human blood, the risk of transmitting infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated. Please see brief summary of prescribing information for Zemaira below. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Based on September 2015 revision.

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

serving others for more than three decades obert (Bob) Nichols was born and raised time of fear in Maryland, and he currently lives in the and doubt, an town of Forrest Hill with his 26-year-old angel arrived at son and 22-year-old daughter. Nichols the right time: smiles when he talks about his family, his AlphaNet “we are a close family unit and spend as much time coordinator, as possible together,” he says; and then an even wider Jenny Faull. smile comes along as he continues: “they are, and “She would call me each month and track me down as I always will be, my inspiration! I feel so blessed to have was in the hospital over 50 times in three years. I didn’t been able to stay in their lives and experience so much make it easy on her, but Jenny never quit trying. She gave with them.” me the reassurance that I wasn’t alone in my battle and that there was a large community behind me. I knew that Nichols is a retired Baltimore County professional if given the chance to work with those in need, I would paramedic/firefighter who served for almost 27 years. consider it an honor and a privilege,” he says. He invested many years of his professional life into becoming one of the highest-trained providers in his Nichols was blessed and received the gift of life with a field. He served as a volunteer for 10 years, sharing his double lung transplant in 2010, which gave him a new skills with others to bring greater awareness to public chance and a new perspective on life. It also came with safety. Nichols spent countless hours teaching people the opportunity of becoming an AlphaNet coordinator, of all ages and occupations in multiple settings and something that he is greatly thankful for. collaborated with his local newspaper on a variety of “I have made lifelong friends, including the donor’s articles to promote safety and good health. family, my companion coordinator who walked with me, Nichols’ passion for serving others and helping the and others who have given me this opportunity to be community benefits AlphaNet in his current role as a here. When I think back over the eight years I have been coordinator for the northeast area of the United States. given and of all those people and events that I would have “I may not be repelling out of a window to rescue missed, I can’t help but feel so blessed,” he explains. someone anymore, but I am grateful to be able to help His diagnosis allowed him and his Alphas in need,” he says. to have a chance at proper “From Maryland to Maine, family For Nichols, this is how it lifestyle changes, treatment and a I strive to provide the same better quality of life. Deep down, he all started: after 15 years of experiencing symptoms that doctors wonderful support that was knew that his new-found purpose believed were due to asthma and his would be to bring this awareness to given to me and continue years of firefighting, he was properly other families in hopes that, with the caring tradition of diagnosed with Alpha-1 Antitrypsin early detection and treatment, other ‘Alphas Serving Alphas.’” Deficiency (Alpha-1) in 2007. Once Alphas can enjoy an improved quality his diagnosis was determined, his of life, like him. “If I can help one family was tested. This revealed three brothers and his person from ever experiencing what I did, then I will feel two children that have the Z gene. I have realized this purpose,” he finishes. A few years after being diagnosed, Nichols’ health Nichols recommends the Alpha-1 Foundation website for began to decline rapidly. He found himself “clinging information about Alpha-1 at www.alpha1.org, and he for life” and felt like he was the only one with this also encourages Alphas to get an AlphaNet coordinator. condition. “It was very frustrating to have had all this To learn more about AlphaNet and the network medical knowledge and not be able to have known of coordinators, please visit their website at what I was dealing with,” Nichols explains. www.alphanet.org. 1 ALPHA-1 FOUNDATION Starting infusions was a difficult ordeal but during this

www.alpha1.org

ALPHA-1 COMMUNITY

Bob Nichols:

(877) 228-7321 | www.alpha1.org

The 2017 COPD National Action Plan was he Alpha-1 Foundation is excited to created in partnership with the Centers for Disease have hosted the 17th Gordon L. Snider Critical Issues Workshop, in Manhattan, Control and Prevention (CDC) and aims to establish a national agenda to address New York, the needs of the 16 million people on Nov. 15, 2018. The who are living with COPD and the Workshop highlighted Alpha-1 is the millions of others who do not realize the National Institutes of leading identified that they have it. The Workshop Health, National Heart, featured three sessions including Lung, and Blood Institute genetic risk factor for discussions and recommendations on (NHLBI) 2017 COPD National Action Plan. developing COPD. the Role of Exacerbations in COPD; COPD Targeted Detection and James Kiley, MD, director Emerging Biomarkers in Alpha-1 of the NHLBI Lung and COPD. The Alpha-1 Foundation’s goal is to Division kicked off the workshop that focused on stimulate discussion and new ideas, and ultimately the role of genetic chronic obstructive pulmonary to publish the proceeds of the Workshop. disease (COPD), or Alpha-1, within the plan.

FRONTIERS

COPD National Action Plan and Alpha-1 working together

The five goals of the 2017 COPD National Action Plan: • Empower people with COPD, their families, and caregivers to recognize and reduce the burden of COPD. • Improve the prevention, diagnosis, treatment, and management of COPD by improving the quality of care delivered across the healthcare continuum. • Collect, analyze, report, and disseminate COPD-related public health data that drive change and track progress. • Increase and sustain research to better understand the prevention, pathogenesis, diagnosis, treatment and management of COPD. • Translate national policy, educational and program recommendations into research and public health care actions. 1 ALPHA-1 FOUNDATION

For more information on the COPD National Action Plan, you can visit www.copd.nih.gov. www.alpha1.org

 With or without lung disease (including those who’ve been transplanted)?  With liver disease?

 Parent of an Alpha child between newborn and 18 years of age? If you answered “yes” to any of these questions, REACH may be for you! AlphaNet’s free REACH program provides you with an Alpha Coordinator to give you the information, education and one-on-one support you need to stay as healthy as possible. You are NOT alone!

For more information about the REACH program, please call (855) 876-8422 or visit www.alphanet.org/REACH to take the free REACH Risk Assessment. Designed specifically for individuals with severely deficient Alpha-1 genes.

IN YOUR INTEREST

Globally connected by a common purpose lpha-1 Global, a program of the Alpha-1 A Foundation, is convening the 7th Alpha-1 Global Patient Congress on April 4-6, 2019, in

Dubrovnik, Croatia Following the 6th Global Patient Congress in Lisbon, Portugal, in April 2017, Alpha-1 Global Dubrovnik, Croatia. This event will bring together has continued to develop avenues for the global patients, physicians and researchers from 40 community to collaborate and learn from each other. countries to exchange new findings about Alpha-1 The need for strengthening the Alpha-1 message Antitrypsin Deficiency (Alpha-1). The congress will and reinforcing patient advocacy were the main start on the evening of April 4, with a reception and topics during the meeting. dinner, and will conclude late Saturday afternoon. “We have a closely-knit Alpha-1 community,” says All Alpha-1 stakeholders will be invited to Gutierrez. “We work hard to provide training for participate in the discussion of solutions to the issues local advocacy and ways for regional collaboration faced by the global Alpha-1 community, including between Alpha-1 leaders.” access to augmentation therapy. Congress attendance in Dubrovnik will broaden The Global Patient Congress aims to: stakeholder relationships around the world and create more deeply engaged patient representatives, • Present the latest trends on Alpha-1 research, inspired to participate in future campaigns, events therapies and patient care and educational opportunities at the national and • Develop strategies to expand access to regional levels. augmentation therapy • Broaden individual awareness and participation to Prior to the Patient Congress, the 4th International Research Conference on Alpha-1 Antitrypsin will inspire local action take place between April 3-4. This is a meeting • Exchange best practices and success stories in for invited researchers and discussants, yet open to advocacy and collaborative efforts any observers interested in Alpha-1 research. The • Provide networking opportunities between Research Conference will end with a reception and patients and experts dinner for both Research Conference participants and Patient Congress participants. Connecting points Adam Wanner, MD, scientific director of the Since its inception in 2013, Alpha-1 Global has connected patients with local associations and assisted Alpha-1 Foundation explains: “This is the fourth time we are combining the International Research association start-ups. Its network has grown to include representatives from the patient, medical and Conference on Alpha-1 with the Global Patient Congress. This set up has proven successful since research communities in more than 40 countries. stakeholder groups in the global Alpha-1 space can “We believe that the close relationships across all convene in one place.” patient, clinician and scientific communities will accelerate earlier diagnosis, disease management and the role of patient registries,” says Gonny Gutierrez, Cristina Barbiero (Italy), mother to director of Alpha-1 Global. “Networking and three Alpha-1 children has been a connecting individuals and organizations is a big vibrant and active leader for many part of what we offer the international community. years within the community. Outside We are globally connected for a common purpose,” of being a busy marketing executive she adds. Beginnings In April 2013, Barcelona, Spain, was the setting for the 4th International Alpha-1 Patient Congress. It was the result of this gathering of leaders from 20 countries and from discussions regarding the community’s successes, failures and needs, that a united resolve to stay connected as a collaborative global patient community was formed. To help assist with the building of a global communications network, the Alpha-1 Foundation offered its leadership and resources. www.alpha1.org

in Milan, she finds the time to create new ways to drive advocacy efforts throughout Italy and inspire other country leaders to do the same.

“It’s my privilege to spearhead the design of an Alpha-1 Awareness Campaign concept for Italy and possibly other countries,” Barbiero states. “We’ve requested input from other country leaders to ensure the best outcome. This is a true collaboration and we look forward to presenting our campaign at the Patient Congress in Dubrovnik.”

For event information please visit: www.alpha-1global.org

1 ALPHA-1 FOUNDATION 21

ASK THE ALPHA DOC

Alpha-1 related lung disease Can an Alpha donate blood? Can they donate their organs? Great question. If you are an Alpha and you have mild or no lung disease, you may be able to donate blood. However, if you are receiving augmentation therapy, because it is made from pooled blood products, then many blood banks will not accept your blood donation. If you have severe lung disease or if you have had a recent infection or exacerbation, it is generally not advised to donate blood. Alphas can certainly donate their organs but will likely not be able to donate their liver nor lungs if there is evidence of lung disease.

Can an Alpha smoke, vape or eat marijuana? Since the risk of developing lung disease related to Alpha-1 Antitrypsin Deficiency (Alpha-1) is significantly increased by smoking, Alpha-1 patients should not smoke. In addition, Alphas should avoid being exposed to second hand smoke, occupational smoke, fumes or particulate matter. Regarding vaping, this should also be avoided. While vaping has been promoted by the tobacco industry as a “safer” form of inhaling tobacco, there is a lot unknown about its safety. The inhaled vaporized fluid contains not only nicotine, but also numerous chemicals. The effects of these inhaled chemicals on the lungs is not known, but there are already reports of patients who have developed

severe lung disease following vaping. Eating marijuana, which may be used as an appetite stimulant or relief of pain and/or anxiety will not pose a lung health risk to Alphas.

What is the connection to lack of oxygen and heart failure? How and why does my lung condition affect my heart? Will this go away post-transplant? If an Alpha develops severe lung disease, he/ she may also develop a problem with their heart known as pulmonary hypertension. Pulmonary hypertension is when the blood pressure within the lungs is too high. It places a strain on the right side of the heart which can cause right heart failure if it progresses. Pulmonary hypertension is caused by two problems in patients with advancing emphysema. First, the lung damage causes injury to the small blood vessels (capillaries). Second, low oxygen levels cause the blood vessels in the lungs to constrict. Both problems in Alpha-1 related lung disease contribute to pulmonary hypertension. Therefore, ensuring adequate oxygenation is an important component to the therapy plan in Alpha-1. The good news is that these problems will resolve after lung transplantation.

1.877.2.CURE.A1 (228.7321)

At what point should an Alpha consider lung transplant? At what percentage of lung function do most lung transplants occur? In general, lung transplantation should be considered as a treatment for Alpha-1 lung disease when the disease has progressed to where it will be difficult for the lungs to support the person’s life over the next one to two years. This can be difficult to estimate so physicians generally use multiple characteristics to help make this determination. One of these characteristics is the degree of airflow obstruction, estimated by FEV1 (the amount of air one can blow out in one second). When FEV1 is lower than 25% of predicted, one should consider referral for transplant evaluation. Other characteristics include low oxygen and high carbon dioxide levels in the blood, pulmonary hypertension, frequent hospitalizations, weight loss and reduced exercise capacity. 1 ALPHA-1 FOUNDATION

Steven R. Hays, MD, during his presentation “Update on Lung Transplantation for Alpha-1” during the Alpha-1 Foundation’s 27th Annual National Education Conference in San Francisco, California, on June 30, 2018.

www.alpha1.org

Our guest physician for the Ask the Alpha Doc section is Steven R. Hays, MD, professor of medicine in the Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, and medical director of the Advanced Lung Disease and Lung Transplant Program of the University of California, San Francisco (USCF). Hays attended Northwestern University before returning to Kansas to attend the University of Kansas School of Medicine, where he obtained his medical degree, completed his residency and served as chief resident in Internal Medicine. He then went to UCSF where he completed specialty training in lung transplant medicine. He has been on the faculty at UCSF since 2003 and has served as the medical director of the Lung Transplant program since 2011. Initially an airway biologist set on understanding the mysteries of bronchiolitis obliterans, Hays shifted his focus to improving lung transplant patient care and outcomes in a more direct way. Over the last 15 years, he has worked with his colleagues in the lung transplant program to develop a patient care system that provides rigorous, consistent and state of the art care while promoting continuous quality improvement using clinical data - a “learning healthcare system.”

ALPHA-1 COMMUNITY

“The job is not done, yet” says advocate

Ken Richmond Making a difference for 17 years

dvocacy plays an important role in our community, more so when it comes to fighting for what is right for those that are most affected by Alpha-1 Antitrypsin Deficiency (Alpha-1): Alphas themselves.

Capitol Hill Advocacy Day in the early 2000s, a project created by John W. Walsh, co-founder of the Alpha-1 Foundation and Miriam O’Day, senior director of public policy for the Foundation at the time (and currently its Interim CEO).

After being diagnosed in 1995, Ken Richmond followed the advice of his doctor, Mark Brantly, MD: keep pushing hard and not to take it easy and relax, due to his condition.

That Hill Day focused on two primary goals: ensuring access to care for Alphas and supporting key legislation that would lead to the formation of the Rare Diseases Clinical Research Network (RDCRN). This program is currently under the National Center for Advancing Translational Sciences (NCATS).

So, he chose to keep pushing hard. Richmond joined the online community and began conversations with Alphas from all over the United States. In 1997 he attended his first National Conference in Framingham, Massachusetts, where he made the decision to actively get involved in the growing Alpha-1 community. The benefits were information, resources, and clinical trials already happening. He started his volunteerism in advocacy with the working group that led the first Alpha-1 24

Richmond participated in the 2008 ruling by the U.S. Department of Transportation to ease access of medical oxygen for airline passengers, a decision that had a direct impact on the Alpha-1 community. The policy change allowed portable oxygen concentrators to be used as carry-on; much like laptop computers. More recently, Richmond was an U.S. Food and Drug Administration (FDA) panel member at

1.877.2.CURE.A1 (228.7321)

the Patient-Focused Drug Development Workshop focused on Alpha-1 in September 2015. He also participated in the creation of a National Action Plan for chronic obstructive pulmonary disease (COPD) in 2016, as well as in the 21st Century Cures Act, passed in 2017, designed to help accelerate medical product development and bring new innovations and advances in technology to patients who need them faster and more efficiently. “The job is not done, yet. From the early 2000s to the present I have been going to Capitol Hill on a regular basis, calling and emailing congressmen in the House of Representatives and the Senate regarding our cause,” said Richmond. “I bring my voice as a patient advocate to Capitol Hill to help our community,” he added.

repurposed therapy is designated to treat a rare disease and obtain an approved rare disease indication from the FDA on the drug label. This could double the number of treatments for rare disease patients. The Access to Precision Medicine Act addresses how to reduce barriers to genetic and genome testing by encouraging the expansion of health insurance coverage of genetic and genomic testing, including diagnostic, predictive and presymptomatic testing, and whole genome sequencing. At a time when the U.S. Federal Government, from the National Institutes of Health (NIH) to the FDA are finding ways to listen, learn and incorporate the patient voice into decisions, we need strong voices like Richmond’s.

As part of the 2018 Rare Disease Day initiative by the National Organization of Rare Disorders (NORD), Please contact Roberto Balderas, grassroots advocacy Richmond attended Rare Disease Week on Capitol manager at the Alpha-1 Foundation, if you would Hill, in Washington DC, which brings the rare like to become an Alpha-1 advocacy ambassador, at disease community members from across the country rbalderas@alpha1.org or call (877) 228-7321 ext. 205. together to be educated on federal legislative issues, If you are interested in advocating on behalf of the meet other advocates, and share their unique stories Alpha-1 community, please register at our Action Center with legislators. He attended, along with the Alpha-1 to get started, at www.alpha1.org/action-center. 1 ALPHA-1 Foundation, the 2018 RDLA (Rare Disease Legislative FOUNDATION Advocates) Legislative Conference, to explore the legislative process, legislation currently under consideration by Congress, and “Richmond has been effective advocacy techniques to working to make build relationships with members a difference and of Congress and staff. to make his voice Richmond held meetings at the heard on Capitol offices of Senator Tim Kaine and Senator Mark Warner, where he Hill for the past supported the Orphan Product 17 years, with the Extensions Now – Accelerating purpose of having Cures and Treatments Act S1509/ that voice turned HR1223, (the OPEN Act), and the Access to Precision Medicine into actions that Act (HR5062), respectively. benefit the Alpha-1 The OPEN Act seeks for community. His biopharmaceutical companies work earned him the to consider repurposing already Alpha-1 Foundation approved therapies for rare National Advocacy diseases, by providing an additional six months of market Award in the exclusivity for the drug being summer of 2017.” repurposed. The sponsor company must demonstrate that the www.alpha1.org

ALPHA LIFE

Steven Shurtz: waiting for the next phase Written by: Richard Lovrich

n a hilltop outside of San Francisco, California, sits a low-slung home that shows only its simple garage doors, a hint of native landscaping and a handsome garden gate to the outside world. That gate, perfect in proportion and carefully crafted in its details, speaks volumes about homeowner Steven Shurtz.

An alpha-1 antitrypsin level test led to genetic testing and by telephone the physician informed Shurtz that “the good news is that we now know what you’ve got, the bad news is that we now have to deal with it.” In 2009 at 59 years of age, Shurtz received his diagnosis of Alpha-1 Antitrypsin Deficiency (Alpha-1).

In 2010, with a diagnosis but no real plan Shurtz began his career as an audio engineer in for oxygen, keeping up with augmentation 1974 at storied EMI studios, advancing to the therapy and without antibiotics, Shurtz position of general manager. After stints at embarked on a whirlwind European journey The Saul Zaentz Film and cinema audio giant for Meyers. In Tallinn, Estonia, he began to Dolby Labs, he ultimately worked for Meyer feel run-down. From Tallinn, he extended Sound, makers of ultra-high-end studio audio his trip to visit post-production facilities in equipment. What they did not make was the United Kingdom where he sought out cinema sound, and responding to a pitch by medical treatment. There he was prescribed Shurtz, Meyer Sound antibiotics. created a cinema line. From the UK, This interview of an Alpha, had become The Dolby Theatre, Shurtz flew to home of the Oscar a conversation between two friends and Amsterdam and, presentations, as before departing from his home on the skipping an audio well as Pixar and trade show, he hill Steven left me with this - “We Alphas Skywalker theaters, checked himself in often hear from others, ‘you look well.’ now use 100 percent to VU University Meyer sound. Hey, it’s only lung disease, right?” Medical Center, a Shurtz first teaching hospital. experienced breathing difficulties in his After test results, the staff informed him that thirties, although with few, full exacerbations. he did not have pneumonia. However, he In an all-too familiar pattern for lung-affected was confined for six days with IV antibiotics, Alphas, these episodes were chalked up to a sentence confirmed by the very large male asthma and allergies. Equally familiar, it took nurse who physically blocked his exit. His many years for his decreasing lung health to wife Joan flew to his side and there they lead him to a pulmonologist. celebrated his 60th birthday. 26

1.877.2.CURE.A1 (228.7321)

Back in the United States, Shurtz resumed travel for work, frequently flying to Los Angeles; flights that were debilitating, prompting him to acquire a portable oxygen concentrator which helped to alleviate his flying fatigue. When his breathlessness increased, full-time oxygen supplementation was prescribed, beginning with two liters pulse. Two became three, three led to four liters and then five liters of full-time continuous flow. By March of 2016, Shurtz was told that he would live for no more than two to three years and that a lung transplant was the only option left to him. It took little convincing for him to embrace the opportunity. Luckily the University of California, San Francisco (UCSF) has a 95 percent survival rate for its lung transplants, the best number in the country. In April 2017, survival became Shurtz’s full-time job, following an amicable split with Meyer Sound. Now on a list, Shurtz waits for the donor lungs that will take him on the next phase of his Alpha-1 journey, a journey along which he has encountered many obstacles. With each new diagnosis, each diminution of his breathing capacity, Shurtz has found the will to fight back, the imagination to adapt and the power to overcome. In April 2018, at home on what would prove to be anything but a normal day, his efforts at breathing suddenly became less effective. With precious breath he called out for his wife Joan, who in turn called 911. Emergency services would arrive within a few,

Joan Shurtz, loving wife and caregiver to Steve Shurtz www.alpha1.org

short minutes, but minutes long enough for Shurtz’s breathing to deteriorate further, time enough for him to wonder if he was going to make it. Once in the ambulance, the team utilized a special machine to force 15 liters of pure oxygen into his body. Fear gave way to a small degree of relief – he was going to be ok – he would survive. Shurtz had suffered a spontaneous pneumothorax, one of his lungs had collapsed. He would spend a total of 12 days in hospital and, always an Alpha that looks on the bright side, he fondly remembers the “two-milliondollar view” of San Francisco and the Bay Bridge from his spacious room at Oakland Medical Center. He is now using a 10-liter per minute concentrator which, centrally located and with a 50-foot hose, allows him full access to his home. At the rate that Shurtz now uses oxygen when out in public or in his yard, a tank does not last very long, and so, he has added a system consisting of five LPM concentrators, attached by a hose to a compressor that can refill special tanks that hold 3000 PSI instead of the normal 2000. That difference is a big one for both his mobility and his independence. At the time of printing, Shurtz was inactivated from the transplant list due to a non-Alpha-1 complication. He is weathering this setback with calm and focus, which have served him well, throughout his Alpha-1 journey. 1 ALPHA-1 FOUNDATION

ALPHA-1 KIDS

A mother to the

rescue D

ara Kass, MD, is a physician originally from Brooklyn, New York, who works as an emergency medicine doctor at Columbia University Medical Center, “but also the mom of three kids and a wife to one husband,” she explains laughing. Sammy is her third child. He was smaller than his siblings and at a little over five pounds at birth, but everything else looked fine. He had a really hard time in the first couple of weeks gaining weight. At six weeks old, a high level of bilirubin in his blood was detected, and just days later he was diagnosed with Alpha-1 Antitrypsin Deficiency (Alpha-1). “We didn’t know that we were carriers. There is no history of Alpha-1, cirrhosis or COPD in our families. We had to go back to our kids, our siblings, and their kids, to figure out how many in our family could be carriers or Alphas,” says Kass. “It’s weird to wrap your head around something you never saw in real life, until it happens to your kid, and that’s what happened to us.” The family joined several Alpha-1 Foundation activities, such as the fundraising walk across the George Washington Bridge, and decided to learn more about the community. But things soon changed; Sammy wasn’t growing out of the liver dysfunction produced by Alpha-1, and around his first birthday he started collecting fluid in his belly, which is a mark of progressive liver disease. In fact, he had scarring in his liver that was not getting any better. The family knew Sammy was going to need a transplant eventually. So, his doctors asked Kass

Dara Kass, MD, and Sammy

whether she would consider being a living donor, and immediately she said yes. “This is when being a doctor helps because I processed all the alternatives, especially how hard it is to get an organ in our area,” Kass remarks. “There were a lot of scary moments. You pray that things work, you pray that everybody wakes up from the anesthesia. There are a lot of things that are scary. It’s a big surgery for a two-year-old. There are a lot of things that can go wrong in a transplant, but Sammy didn’t have any of that. There is some pain and discomfort, but it’s totally worth it,” remembers Kass. Kass says that it is normal for mothers in this situation to be sad sometimes and it’s okay to be happy sometimes too. Those emotions come in waves and you can appreciate the good days and you can be sad on the bad days, and that’s fine. After the transplant, Kass started giving a lecture annually on Sammy as a case study, at the New York University (NYU) Medical Center, and they bring in two Alpha-1 patients to meet medical students every year. So, now Sammy goes with 1.877.2.CURE.A1 (228.7321)

these two other Alpha-1 patients every year and they talk about the transplant, about living with Alpha-1, and put a face to Alpha-1 for medical school students in the first year of medical school. Kass explains that she takes advantage of the resources in the Alpha-1 community, and that the science is moving forward. The Foundation helped her, and she thinks it can help everybody in different ways. “You can be afraid and be uncertain, it can be scary, but it’s important to appreciate everything that is positive. It’s never that bad. There is always going to be a better day ahead of you. I find, and it makes me sad, a lot of people get consumed by this. It defines how they see their kids every day. It defines how they see themselves. And they lose the joy of other moments of their life. We can do it, together, whatever that is, whoever your together is,” confessed Kass. From left to right: Dara, Sammy (6), Michael, Charlie (9), Hannah (11)

A father to the rescue “Two weeks after he was born, in 1989, my son William showed signs of jaundice and the pediatrician ordered blood work. In a follow-up appointment, they told us he had Alpha-1 and may someday need a liver transplant. In 1994, at five years of age, he was listed for a transplant. We had begun to hear of experimental living transplants being done in Europe and then in Chicago. Finally, in late spring of 1997 the transplant coordinator asked if we were interested in a living transplant, and we jumped at the chance. We were both tested, and my husband was a better match, so on July 15, 1997, my son received a piece of my husband’s liver. My son was on medication for years, but now he isn’t taking any meds. He is 29 years old, and I knock on wood as I say this, he has never had an episode of rejection. We have two other children. Our oldest son James is 31 and a ZZ, and our daughter Katie is 30 and an MZ. I am so glad there is a network for families. I remember when I visited the pediatrician’s William Neville, Becky Neville, James Neville, Markelle Veldez, office 29 years ago, he had never heard of Owen Neville, Katie Neville and Zoe Neville Alpha-1 and had no idea how to have my other two kids tested.” - Becky Neville 1 ALPHA-1 FOUNDATION www.alpha1.org

2019 Educational Scholarships Every year the Alpha-1 Foundation awards educational scholarships to Alphas and their immediate family (children, grandchildren and spouses) to assist those in need to further their education. The application cycle begins in February and the deadline for submissions is April 1st, 2019. awards, granted in June, honor the memory of Alphas who have made a The awa difference within the Alpha-1 community.

For more information, please visit: a1f.org/EducationalScholarships

BIORX IS NOW KNOWN AS

STILL PROVIDING: • Home delivery of multiple alpha-1 augmentation therapies • In-home nursing, caregiver venipuncture training, and drug administration customized to your needs • Access to a pharmacist 365 days a year, 24 hours a day • Expert reimbursement support team • Personal Alpha-1 Solutions advocates for treatment support and resource assistance

WE’RE STRONGER TOGETHER. FOR MORE INFORMATION

CALL: 866.442.4679 VISIT: diplomat.is/specialtyinfusion

28TH ANNUAL NATIONAL CONFERENCE June 21-23

Orlando, FL

SUPPORT GROUP MEETINGS December 2018 Dec. 1 Midwest Alphas Kansas City, MO Southeast Keystone Alphas Hershey, PA Alpha Gators West Palm Beach, FL CT Nutmeggers New Britain, CT Northern Indiana Alphas Fort Wayne, IN Northern Virginia (NOVA) Fairfax, VA Hoosier Alphas Carmel, IN SoCal Roadrunners Palm Desert, CA Glass City – Toledo Alphas Toledo, OH West Virginia Better Together Alphas Princeton, WV Gainesville, FL Alphas Gainesville, FL Dec. 2 Alpha Opportunities King of Prussia, PA Dec. 3 South Central Washington Alphas Kennewick, WA Dec. 6 Massachusetts Alphas Needham, MA Dec. 8 Sacramento Alphas Roseville, CA Alabama Alphas Birmingham, AL O2 Seekers of Bakersfield, CA Bakersfield, CA VA Alpha-1 Connection Richmond, VA Washington Alphas Auburn, WA West Texas Alphas Lubbock, TX AlphaBurgherZ Monroeville, PA Alpha-1 Naples Naples, FL Dec. 9 Central Georgia Alphas Johns Creek, GA Dec. 12 Alphazonies Scottsdale, AZ Dec. 13 Strickly Alphas Wheelersburg, OH Dec. 15 NY/NJ Alphas New York, NY Tampa, FL Alphas Lutz, FL Alpha Okies SG Oklahoma City, OK Dec. 21 Arkansas Alphas Benton, AR January 2019 Jan. 9 Alphazonies Jan. 12 Alpha-1 Naples VA Alpha-1 Connection

Scottsdale, AZ Naples, FL Richmond, VA

Jan. 19 Jan. 26

Reno/Tahoe Alphas Kentucky Alphas Buckeye Alphas Bayou City Alphas FL Gulf Coast Alphas Heart of Georgia Alphas Dallas/Fort Worth Alphas

Reno, NV Shepherdsville, KY Columbus, OH Houston, TX Sarasota, FL Macon, GA Arlington, TX

February 2019 Feb. 2 Northern Virginia (NOVA) SoCal Roadrunners San Diego Alphas Feb. 5 Northwest Arkansas Alphas Feb. 9 Norfolk, VA Alphas Northwest Indiana Alphas Feb. 12 Southwest Missouri Alphas Feb. 13 Alphazonies Feb. 15 Arkansas Alphas Feb. 16 Alphas of Northern Illinois North Alabama Alphas Sacramento Alphas Feb. 23 Alabama Alphas Illiana Alphas

Fairfax, VA Palm Desert, CA Oceanside, CA Fayetteville, AR Norfolk, VA Dyer, IN Joplin, MO Scottsdale, AZ Benton, AR Rockford, IL Huntsville, AL Roseville, CA Birmingham, AL Terra Haute, IN

March 2019 Mar. 2 Alpha Gators Mar. 9 St. Louis Alphas Washington Alphas Chicagoland Alphas Mar. 13 Alphazonies Mar. 14 Strickly Alphas Mar. 16 Utah Alphas Maryland Alphas Kentucky Alphas Idaho Alpha-1 Connection

Miami, FL St. Louis, MO Auburn, WA Wood Dale, IL Scottsdale, AZ Wheelersburg, OH South Jordon, UT Severna Park, MD Shepherdsville, KY Boise, ID

2018-2019 CALENDAR

ALPHA-1 EDUCATION DAYS March 9 Phoenix, AZ August 3 Denver, CO March 30 St. Louis, MO September 28 Minneapolis, MN May 4 Portland, OR October 26 Philadelphia, PA For more information about Education Days, contact Kim Caraballo, (877) 228-7321, ext. 323 or ycaraballo@alpha1.org.

For more information about Support Group Meetings, contact Barbee Bennington, (877) 228-7321, ext. 227 or bbennington@alpha1.org. BUILDING FRIENDS FOR A CURE (BFC) EVENTS Feb. 15 Friends for A Cure, 80’s Dance Party – Feel the Love Jacksonville, FL Sarah & Richard Johnson friendsforacure@comcast.net Mar. 2 Celtic Connection Boston, MA Bob Healy & Fred Walsh bobhealy125@msn.com Apr. 27 Hero Walk Richmond, VA Pam VanScoy vaalpha1herowalk@yahoo.com May. 11 George Washington Bridge Walk New York/New Jersey Joe Reidy joereidy@verizon.net Jun. 8 Iowa Scoop/Walk Johnston, IA Peg Iverson pegiver@mchsi.com For more information on Building Friends for a Cure, please contact Angela McBride, (877) 228-7321 ext. 233 or amcbride@alpha1.org.

SAVE THE DATE

28th Annual National Education Conference JUNE 21 - 23, 2019

Visit a1f.org/alpha1conference for more information

For more information, visit a1f.org/alpha1conference

Please visit the calendar at alpha1.org for more information on these support group meetings and other upcoming events. www.alpha1.org

ALPHA-1 1 FOUNDATION

NONPROFIT ORG U.S. POSTAGE PAID MIAMI, FL PERMIT # 8124

3300 Ponce de Leon Blvd. • Coral Gables, FL 33134

Alpha-1 research studies enrolling The best way to learn about studies you might qualify for is to join the Alpha-1 Research Registry. Here is a list of studies now enrolling volunteers: ADVM-043 Gene Therapy Study Investigational gene therapy treatment study for ZZ and Z/ Null Alphas over the age of 18. Participation lasts 15 months and multiple sites are recruiting. Visit https://clinicaltrials. gov/ct2/show/NCT02168686 for more information.

GLASSIA Study Augmentation therapy study for severely deficient Alphas. Multiple sites recruiting. The study duration is 6 months. Visit https://clinicaltrials.gov/ct2/show/NCT02525861 for more information.

Alpha-1 Carbamazepine Study Study for ZZ or SZ Alphas between 14-80 years old with severe liver disease to test if the drug carbamazepine improves liver disease. Visit https://clinicaltrials.gov/ct2/ show/NCT01379469 for more information.

Lung Imaging Study Columbia University (NY) study for adults aged 45-80 with Alpha-1 or Alpha-1 carrier state with OR without COPD. Visit https://clinicaltrials.gov/ct2/show/NCT02978144 for more information.

Alpha-1 Foundation Liver Study Study for Adult ZZ Alphas to determine the causes and progression of liver disease. “Known Severe Liver Disease” and “Post-Transplant” groups still enrolling. (Liver Biopsy groups ended enrollment). Visit https://clinicaltrials.gov/ ct2/show/NCT02014415 for more information.

O2VERLAP Study COPD Foundation and American Sleep Apnea Association study for adults aged 40 and up diagnosed with both COPD and Obstructive Sleep Apnea (OSA), and with a prescription for CPAP therapy. Study is testing a “virtual classroom” where patients can learn how to best use their machines and improve their self-care. Visit https://clinicaltrials.gov/ct2/show/ NCT03446768 or www.O2VERLAP.org for more information.

COPD Exacerbation Study Columbia University (NY) study for adults aged 35-80 with Alpha-1 or Alpha-1 carrier state AND physician diagnosed COPD. Visit https://recruit.cumc.columbia.edu/clinical_ trial/1523 for more information.

SPARTA Study Augmentation therapy study for severely deficient Alphas. Multiple sites recruiting. The study duration is 3 years. Visit https://clinicaltrials.gov/ct2/show/study/ NCT01983241 for more information.

Hyaluronic Acid Inhalation Study Inhaled therapy study for severely deficient Alphas diagnosed with Emphysema. Multiple sites recruiting. Visit https://clinicaltrials.gov/ct2/show/NCT03114020 for more information.

For more information about these studies or to enroll in the Alpha-1 Research Registry, call 877-886-2383 or visit alphaoneregistry.org