Clinical Alert - May 2020

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MAY 2020










EXECUTIVE EDITOR Anna Schreck Bird PharmD DEPUTY EDITORS Jessica Czechowski PharmD Lara Frick PharmD, BCPS, BCPP Carole Kerzic RPh Leslie Pittman PharmD

TRENDING TOPICS NEW MULTIPLE SCLEROSIS DRUG The United States (US) Food and Drug Administration (FDA) has approved ozanimod (Zeposia®), a new oral medication for multiple sclerosis (MS). Ozanimod is indicated for the treatment of relapsing forms of MS in adults, including clinically isolated syndrome, relapsingremitting disease, and active secondary progressive disease. This sphingosine 1-phosphate (S1P) receptor modulator inhibits the ability of lymphocytes to leave the lymph nodes, thereby decreasing lymphocytes in the peripheral blood. Although the exact mechanism by which ozanimod acts in MS is not fully known, it may be related to decreasing lymphocytes in the central nervous system (CNS). FDA approval of ozanimod was based on efficacy and safety findings from 2 randomized, active-controlled, phase 3 studies evaluating 2,659 patients with relapsing MS: SUNBEAM and RADIANCE. In these trials, ozanimod was compared to 30 mcg of interferon (IFN) beta-1a given intramuscularly (IM) once weekly. Ozanimod was dosed as 0.92 mg orally once daily, following dose titration. The primary endpoint, the annualized relapse rate (ARR) over 12 months (SUNBEAM) or 24 months (RADIANCE), was significantly lower in ozanimod-treated patients compared to patients who received IFN beta-1a, with a 38% to 48% relative reduction, respectively (p<0.0001). Ozanimod is contraindicated in patients with recent cardiovascular (CV) events within the past 6 months. It is also contraindicated in patients with certain underlying cardiac conduction abnormalities. Patients with severe untreated sleep apnea, as well as those who are currently taking a monoamine oxidase (MAO) inhibitor, should not receive ozanimod. Ozanimod carries a number of warnings/precautions, including increased risk of infection (e.g., potential for progressive multifocal leukoencephalopathy [PML]).

2 | MAY 2020

Due to the safety profile, a number of assessments are required prior to the first dose, including a complete blood count (CBC) with lymphocytes, an electrocardiogram (ECG) to evaluate for preexisting conduction abnormalities, liver function tests, and varicella zoster virus (VZV) antibody testing. Patients with a history of uveitis or macular edema also require an ophthalmic assessment, and all patients should be evaluated for concurrent or past immunosuppressant medications. Ozanimod joins fingolimod (Gilenya®) and siponimod (Mayzent®) as the third approved oral agent within the S1P receptor modulator class, all of which are approved for relapsing forms of MS. Siponimod and ozanimod are approved for use only in adults, whereas fingolimod is indicated in patients ≥ 10 years of age. In contrast to the other 2 agents in this class, first dose monitoring is not required for ozanimod in the product labeling. Moreover, ozanimod does not require pre-treatment genetic testing as required prior to initiation of siponimod. Ozanimod will be available in 3 capsule strengths, 0.23 mg, 0.46 mg, and 0.92 mg, allowing for the 7-day up-titration schedule of 0.23 mg once daily on days 1 to 4, 0.46 mg once daily on days 5 to 7, and 0.92 mg once daily on day 8 and thereafter. Capsules should be swallowed whole and can be taken with or without food. The manufacturer, Bristol-Myers Squibb (BMS), announced that the launch of ozanimod has been postponed due to the COVID-19 pandemic; they plan to collaborate with the healthcare community to determine availability timeline.

TRENDING TOPICS continued RANITIDINE MARKET REMOVAL The FDA has requested that all manufacturers immediately withdraw ranitidine (Zantac®, generics) products, including both prescription and over-the-counter (OTC) formulations, from commercialization in the US, due to potential for the N-nitrosodimethylamine (NDMA) impurity to increase in the product over time, especially when stored above room temperature. The resulting increase in NDMA may lead to levels above the FDA’s acceptable daily intake threshold. As a result of the immediate market withdrawal, ranitidine products will no longer be available for use in the US. The FDA first became aware of the NDMA impurity in ranitidine during the summer of 2019. NDMA is classified as a probable human carcinogen. Low levels of NDMA, as found in food and water, do not pose a risk for cancer; however, ingesting higher than the recommended amount over an extended period of time may increase the likelihood of cancer. The FDA is advising patients with a ranitidine prescription to speak with their healthcare provider (HCP) about treatment alternatives for their condition prior to discontinuing their medication. Patients who are taking OTC ranitidine are advised to immediately stop taking and dispose of the medication. Other approved prescription and OTC products are available that do not carry the risk of NDMA exposure, for those patients who require continued treatment.

COVID-19: NOTABLE DEVELOPMENTS The National Institute of Health (NIH) and the Foundation for the NIH have launched a new partnership with other public and private institutions to support the development of vaccines and other therapies for COVID-19. This new international collaboration, Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), involves various pharmaceutical manufacturers, the FDA, the Centers for Disease Control and Prevention (CDC), the European Medicines Agency (EMA), and other organizations. ACTIV’s efforts will include implementing a process for prioritization of vaccine and drug candidates, streamlining clinical studies, and sharing resources to increase the development of therapies for COVID-19.

3 | MAY 2020

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The FDA has initiated a new program, the Coronavirus Treatment Acceleration Program (CTAP), for expediting the development of novel treatments for COVID-19. As of April 19, 2020, the special emergency program reported 72 therapeutic agents in trials and 211 in the planning stages. As of mid-April, the FDA had received more than 900 inquiries regarding potential COVID-19 drugs in development and plans to review these in order of strongest scientific merit. Moreover, the FDA is coordinating efforts for the development of blood-related therapies, including convalescent plasma and hyperimmune globulin. At the end of March, the FDA issued emergency use authorizations (EUAs) for hydroxychloroquine sulfate and chloroquine phosphate tablets. This was to allow product from the Strategic National Stockpile to be used to treat adult and adolescent patients who are hospitalized with COVID-19 when a clinical trial is not available or participation in a trial is not feasible. At the end of April, the FDA issued a drug safety communication due to the potential for both of these medications to cause abnormal heart rhythms which can be life-threatening. The FDA states that using these drugs alone or in combination with azithromycin should only be done within a clinical trial or under the circumstances dictated by the EUA; the FDA will provide additional information regarding these risks as data becomes available. The FDA also recently announced prioritization for the review of any submitted Abbreviated New Drug Applications (ANDAs) for hydroxychloroquine and chloroquine. Regarding other drugs and therapies that the FDA is responsible for reviewing for approval, the agency currently has been able to meet program user fee goals for the New Drug Program, the Generic Drug Program, and the Biologics and Biosimilars Performance Programs; however, they have stated that it may not be possible to continue this performance level due to COVID-19 efforts. Reprioritization will occur, as needed, to address drug shortages and supply chain issues. The American College of Rheumatology (ACR) issued guiding principles on allocation of hydroxychloroquine during the pandemic, since it is a therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. ACR recommendations include maintaining adequate supplies of hydroxychloroquine for all

TRENDING TOPICS continued COVID-19: NOTABLE DEVELOPMENTS continued patients requiring the medication. Product should be allocated for SLE patients, especially pregnant patients, as even a short disruption of therapy may result in a flare or necessitate a switch to another therapy with lower efficacy and/or safety. For use in COVID-19 patients, product is recommended to be allocated to allow for study in clinical trials as preand post-exposure prophylaxis, as well as for active cases. Allocation decisions are recommended to be based on local supply of hydroxychloroquine and adjusted as needed with time. Hydroxychloroquine should not be used for COVID-19 prophylaxis in an unrestricted manner unless there is clinical trial data demonstrating efficacy in this setting. The Infectious Diseases Society of America (IDSA) published guidelines on management of hospitalized patients with COVID-19 recommending, in the context of a clinical trial, the following: hydroxychloroquine or chloroquine, corticosteroids for patients with acute respiratory distress syndrome (ARDS), and convalescent plasma (knowledge gap recommendation). The following are recommended only in the context of a clinical trial: hydroxychloroquine or chloroquine plus azithromycin, lopinavir/ritonavir (Kaletra®), or tocilizumab (Actemra®) (knowledge gap recommendation). IDSA suggests against the use of corticosteroids in patients with COVID-19 pneumonia (conditional recommendation). The American Thoracic Society (ATS) has issued interim guidance on management of COVID-19 pending empirical evidence. For hospitalized patients with COVID-19 and pneumonia, they advise that hydroxychloroquine or chloroquine may be used on a case-by-case basis if the patient’s condition is severe and the drug is not in short supply. For outpatients with COVID-19 or hospitalized patients without pneumonia, ATS made no recommendation for or against use of hydroxychloroquine or chloroquine. For hospitalized patients with COVID-19 who have evidence of pneumonia, ATS makes no suggestion for or against the investigational agent remdesivir, lopinavir/ ritonavir, tocilizumab, or systemic corticosteroids.

4 | MAY 2020

The NIH has released a “living” document guideline to assist HCPs in the treatment of COVID-19 patients. Recommendations will be updated frequently as new data becomes available. Pre- and post-exposure prophylaxis are not recommended outside the setting of a clinical trial (strong recommendation; expert opinion). Furthermore, they do not recommend additional laboratory testing or a specific treatment for suspected or confirmed cases of asymptomatic or pre-symptomatic disease (strong recommendation; expert opinion). Currently, data are insufficient to recommend for or against use of antiviral agents or immunomodulatory drugs for patients with mild, moderate, severe, or critical disease (strong recommendation; expert opinion). These treatment recommendations are not designed to be used as mandates; treatment is recommended to be individualized for each patient by their provider. On May 1, 2020, the FDA issued an EUA allowing for the distribution and use of the investigational antiviral drug remdesivir in the US. The EUA allows for the use of remdesivir for treating suspected or laboratoryconfirmed COVID-19 in children and adults who are hospitalized with severe disease characterized by low blood oxygen levels, requirement for oxygen therapy, a mechanical ventilator, or extracorporeal membrane oxygenation (ECMO). Preliminary clinical trial data suggest remdesivir may help shorten the time to recovery in hospitalized COVID-19 patients with severe disease. Remdesivir is administered in a hospital, inpatient setting via intravenous (IV) infusion by a HCP. For more resources on COVID-19, visit the Magellan Rx Coronavirus (COVID-19) Update webpage. For the most current information, visit the FDA, the CDC, the NIH, and the World Health Organization (WHO). State and local health departments also provide valuable information regarding management in local communities.


CORNER VA AND DOD CHRONIC INSOMNIA AND SLEEP APNEA PRACTICE GUIDELINES The US Department of Veterans Affairs (VA) and US Department of Defense (DoD) Evidence-Based Practice Work Group has published clinical practice guidelines for the management of chronic insomnia disorder and obstructive sleep apnea (OSA). The guideline is designed to be used by HCPs to assist in the evaluation, treatment, and management of VA and DoD patients with either of these sleep disorders. The guidelines contain 41 recommendations. For the diagnosis and assessment of OSA, the work group suggests that patients with sleep symptoms be screened using the STOP questionnaire to determine risk for OSA. While polysomnography remains the gold standard for diagnosis of OSA, the work group suggests use of a manually scored type III home sleep apnea test (HSAT), using an event index ≥ 15 events per hour, to establish a diagnosis of moderate to severe OSA in patients with high pretest probability for OSA. For patients with a high pretest probability and a nondiagnostic HSAT result, the guideline recommends repeat testing with the HSAT or polysomnography. For diagnosis of chronic insomnia disorder, evaluation includes self-reported measurements, as well as detailed assessment of sleep, medical, substance, and psychiatric history. For treatment of OSA, positive airway pressure (PAP) is recommended for the entire duration of each sleep period. The panel suggests continuing PAP for the management of OSA even if the duration of use is < 4 hours per night in order to improve adherence. Additionally, patients should be provided educational, behavioral, and supportive strategies to enhance adherence early in treatment. Opioids, as well as sedative hypnotics and alcohol, can potentially exacerbate OSA and therefore should be avoided or used cautiously.

5 | MAY 2020

For the treatment of chronic insomnia disorder, the guidelines recommend cognitive behavioral therapy for insomnia (CBT-I), which modifies sleep-specific thoughts and behaviors. Behavioral components of CBT-I include sleep restriction therapy, stimulus modification, relaxation techniques, and education on sleep hygiene. Cognitive components focus on changing maladaptive thoughts regarding sleep. The work group suggests CBT-I as first-line therapy for the treatment of chronic insomnia disorder over pharmacotherapy. Additionally, the guidelines suggest against the use of sleep hygiene education alone for chronic insomnia disorder. The guidelines state that nonpharmacological interventions for the treatment of insomnia are more effective than pharmacotherapy; however, the work group recognizes that some patients will require short-term pharmacotherapy. For patients in whom a short course of pharmacotherapy is appropriate, low-dose doxepin (3 mg or 6 mg) or a nonbenzodiazepine benzodiazepine receptor agonist (BZRA) (e.g., zolpidem [Ambien®], zaleplon [Sonata®], eszopiclone [Lunesta®]) is suggested. If a nonbenzodiazepine BZRA is utilized, the lowest effective dose should be used for the shortest duration, and patients should be counseled regarding risks of these medications. Evidence is currently inadequate to recommend for or against use of either ramelteon (Rozerem®) or suvorexant (Belsomra®) for chronic insomnia disorder. Benzodiazepines, trazodone, and antipsychotics are suggested against for the treatment of chronic insomnia disorder. In addition, the work group suggests against the use of the following OTC or herbal agents for the treatment of chronic insomnia disorder: diphenhydramine, melatonin, valerian, chamomile, and kava. Additional research evaluating the combination of treatment strategies for OSA and insomnia is warranted, as well as comparative effectiveness studies assessing various treatment modalities.


HIGHLIGHTS • Amneal has issued a voluntary consumer-level recall of 3 lots of nizatidine oral solution 15 mg/mL packaged in 480 mL bottles due to detection of NDMA above the established FDA limit. Product was distributed nationwide by Gemini Laboratories, a subsidiary of Amneal. Consumers with affected product should stop taking the medication and can contact Inmar for further instructions. • Avet has issued a voluntary consumer-level recall of 8 lots of tetracycline HCl capsules USP, 250 mg and 500 mg in 100-count bottles. The recall is due to low out-of-specification dissolution test results which could result in low drug levels in the body and treatment failure. Product was distributed under the Heritage Pharmaceuticals’ label. • The US Preventive Services Task Force (USPSTF) recently expanded their recommendation for hepatitis C virus (HCV) infection screening to include all adults aged 18 to 79 years (recommendation grade B); previously, only adults born between 1945 and 1965 were recommended for screening, as well as others who were at high risk. For the majority of adults, a one-time screening is recommended; however individuals with continued risk (e.g., past or current injection drug use) should be screened periodically. Similarly, in areas where the HCV infection rate is ≥ 0.1%, the CDC recommends that all adults be screened at least once and all pregnant women be screened with each pregnancy. • Cannabidiol oral solution (Epidiolex®), previously designated a Schedule V controlled substance, has been descheduled and is no longer considered to be a controlled substance by the Drug Enforcement Agency (DEA). Epidiolex is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome in patients ≥ 2 years of age. It was descheduled due to its low potential for abuse and established medical use.

6 | MAY 2020

• The American Society of Hematology (ASH) published updated guidelines on the management of immune thrombocytopenia (ITP). The update provides recommendations regarding managing ITP in children and adults, including those who are newly diagnosed and those with persistent and chronic disease who are refractory to first-line treatment with non-lifethreatening bleeding. A variety of potential management modalities are detailed for these patients, including pharmacological therapies (e.g., corticosteroids, IV immunoglobulin, anti-D immunoglobulin, rituximab, and thrombopoietin receptor agonists). • Cenobamate (Xcopri®) has been scheduled by the DEA as a Schedule V controlled substance. Cenobamate oral tablet was approved in November 2019 for the treatment of partial-onset seizures in adults. Launch is expected in Spring 2020. • The FDA has approved Cipla’s generic version of Proventil® HFA (albuterol sulfate) metered dose inhaler. It is indicated for patients ≥ 4 years of age for the prevention of exercise-induced bronchospasm, as well as for the treatment or prevention of bronchospasm in patients with reversible obstructive airway disease. Cipla has stated that shipments will be released in an allocated manner and that product will be donated due to the COVID-19 pandemic. An authorized generic version of Proventil is already commercially available. • The FDA has reported that 3 brand-name pain medications manufactured by Janssen will be permanently discontinued as a business decision. These products include brand-name versions of fentanyl extendedrelease film (Duragesic®), acetaminophen/tramadol tablets (Ultracet®), and tramadol tablets (Ultram®). The agency is recommending that these medications remain on formularies until July 31, 2021, October 31, 2022, and September 30, 2022, respectively, when the last batch of each product expires.







nadofaragene firadenovec FDK Therapies

• Intravesical • Gene therapy

Bladder cancer (Bacillus CalmetteGuérin [BCG] unresponsive, nonmuscle invasive)

May-Jun 2020

olaparib (Lynparza®) AstraZeneca

• Oral • Poly ADP-ribose polymerase (PARP) inhibitor

Prostate cancer

May-Jun 2020

ticagrelor (Brilinta®) AstraZeneca

• Oral • P2Y12 inhibitor

Atherosclerosis in patients with type 2 diabetes mellitus (T2DM)

May-Aug 2020

omalizumab (Xolair®) Genentech

• SC • Anti-IgE antibody

Nasal polyposis

May-Sept 2020

padeliporfin di-potassium Steba Biotech

• IV • Photosensitizer

Prostate cancer (localized)


avapritinib (Ayvakit™) Blueprint Medicines

• Oral • Tyrosine kinase inhibitor

Gastrointestinal stromal tumor (4th-line)


dasotraline Sumitomo Dainippon

• Oral • Serotonin, norepinephrine, dopamine reuptake inhibitor

Binge eating disorder


rucaparib (Rubraca®) Clovis Oncology

• Oral • PARP inhibitor

Prostate cancer (BRCA 1/2 mutant, recurrent, metastatic castrateresistant)


apomorphine Sumitomo Dainippon

• Oral transmucosal • Dopamine receptor agonist

Parkinson’s disease (off-episodes)


artesunate La Jolla

• Dosage form not specified • Antimalarial

Malaria (severe)


L-lactic acid/citric acid/ potassium bitartrate Evofem

• Intravaginal • pH buffer



dupilumab (Dupixent®) Regeneron

• SC • Interleukin-4 (IL-4) inhibitor

Atopic dermatitis (ages 6 to 11 years)


IV = intravenous; SC = subcutaneous

7 | MAY 2020




New Drugs ferric pyrophosphate citrate (Triferic AVNU®) Rockwell Medical

• NDA approval 03/27/2020 • Indicated for the replacement of iron to maintain hemoglobin in adults with hemodialysis-dependent chronic kidney disease (HDD-CKD); not intended for use in patients receiving peritoneal dialysis and has not been studied in patients receiving home hemodialysis • Iron replacement product • Injection: 6.75 mg iron (III) per 4.5 mL solution in single-dose luer lock ampule • Recommended dosage is 6.75 mg iron (III) administered IV over 3 to 4 hours at each hemodialysis session via pre-dialyzer infusion line, post-dialyzer infusion line, or a separate connection to the venous blood line • Product availability is expected following completion of evaluation programs occurring in the 3Q 2020

levonorgestrel/ethinyl estradiol (no trade name) Exeltis

• 505(b)(2) NDA approval 03/30/2020 • Indicated for use by females of reproductive potential to prevent pregnancy • Combination hormonal contraceptive • Oral tablets: 21 active tablets (white-colored), each containing levonorgestrel 0.1 mg/ethinyl estradiol 0.02 mg, and 7 inactive tablets (peach-colored) • Recommended dosage is either 1) swallow whole on an empty stomach or 2) chew then swallow immediately with a full glass of 8 ounces of water on an empty stomach, started on day 1 or on a Sunday and taken at the same time each day in the order directed on the blister pack • Boxed warning for cigarette smoking and serious CV events

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

8 | MAY 2020



New Drugs continued coagulation factor VIIa recombinant-jncw (Sevenfact®) Hema Biologics

• BLA approval 04/01/2020 • Indicated for the treatment and control of bleeding episodes in patients ≥ 12 years of age with hemophilia A or B with inhibitors; not indicated for congenital factor VII deficiency • Coagulation factor VIIa • Injection: 1 mg and 5 mg lyophilized powder in single-use vial • Recommended dosage is weight-based and dependent on severity of bleeding; for mild to moderate bleeds, 75 mcg/kg IV every 3 hours until hemostasis is achieved or a loading dose of 225 mcg/kg IV and if hemostasis is not achieved within 9 hours, then additional doses of 75 mcg/kg IV every 3 hours until hemostasis; for severe bleeds, a 225 mcg/kg IV dose, followed if needed 6 hours later with 75 mcg/kg IV every 2 hours • Boxed warning for thrombosis

selumetinib (Koselugo™) AstraZeneca

• NDA approval 04/10/2020; Breakthrough Therapy, Orphan Drug, Priority Review, Rare Pediatric Disease Designation • Indicated for the treatment of pediatric patients ≥ 2 years of age with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) • Mitogen-activated protein kinase kinases 1 and 2 (MEK 1/2) inhibitor • Oral capsules: 10 mg and 25 mg • Recommended dosage is 25 mg/m2 twice daily, approximately every 12 hours, on an empty stomach until disease progression or unacceptable toxicity; reduce the dose to 20 mg/m2 twice daily for moderate hepatic impairment (Child-Pugh B)

mitomycin (Jelmyto™) Urogen

• 505(b)(2) NDA approval 04/15/2020; Breakthrough Therapy, Orphan Drug, Priority Review • Indicated for adults with low-grade upper tract urothelial cancer (LG-UTUC) • Alkylating agent • Pyelocalyceal solution: Two 40 mg single-dose vials (SDV) of mitomycin and 1 vial of 20 mL sterile hydrogel for reconstitution • Recommended dosage is 4 mg per mL instilled via ureteral catheter or nephrostomy tube, with total instillation volume not to exceed 15 mL given once weekly for 6 weeks; for patients with a complete response 3 months following initiation, instillations can be administered once a month for a maximum of 11 additional instillations; administer 1.3 g of oral sodium bicarbonate the evening before, the morning of, and 30 minutes prior to the instillation procedure • Product availability is expected in 2Q 2020

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

9 | MAY 2020



New Drugs continued ephedrine sulfate (Emerphed™) Nexus

• 505(b)(2) NDA approval 04/17/2020 • Indicated for the treatment of clinically important hypotension in the setting of anesthesia • Sympathomimetic amine • Injection: 50 mg/10 mL ephedrine sulfate (equivalent to 38 mg/10 mL ephedrine base) in a ready-to-use SDV • Recommended dosage is 5 mg to 10 mg administered by IV bolus with additional boluses as needed; maximum total dose of 50 mg

pemigatinib (Pemazyre™) Incyte

• NDA approval 04/17/2020; Accelerated Approval, Breakthrough Therapy, Orphan Drug, Priority Review • Indicated for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test; continued approval may depend on confirmatory trial results • Kinase inhibitor • Oral tablets: 4.5 mg, 9 mg, 13.5 mg • Recommended dosage is 13.5 mg once daily for 14 consecutive days, followed by 7 days off in 21-day cycles continued until disease progression or unacceptable toxicity • Immediate launch is expected

tucatinib (Tukysa™) Seattle Genetics

• NDA approval 04/17/2020; Breakthrough Therapy, Orphan Drug, Priority Review, Project Orbis, Real-Time Oncology Review (RTOR) • Indicated in combination with trastuzumab and capecitabine for adults with advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, including patients with brain metastases, who have received ≥ 1 prior anti-HER2-based regimens in the metastatic setting • Tyrosine kinase inhibitor • Oral tablet: 50 mg and 150 mg • Recommended dosage is 300 mg twice daily with or without food until disease progression or unacceptable toxicity; reduce the dose to 200 mg twice daily in severe hepatic impairment

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

10 | MAY 2020



New Drugs continued sacituzumab govitecanhziy (Trodelvy™) Immunomedics

• BLA approval 04/22/2020; Accelerated Approval, Breakthrough Therapy, Priority Review • Indicated for the treatment of adults with metastatic triple-negative breast cancer (mTNBC) who have received ≥ 2 prior therapies for metastatic disease; continued approval may depend on confirmatory trial results • Trop-2-directed antibody and topoisomerase inhibitor conjugate • Injection: 180 mg lyophilized powder in SDVs for reconstitution • Recommended dosage is 10 mg/kg via IV infusion once weekly on days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity; premedicate to prevent infusion reactions and chemotherapy-induced nausea and vomiting • Boxed warning for neutropenia and diarrhea

opicapone (Ongentys®) Neurocrine Biosciences

• NDA approval 04/24/2020 • Indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes • Catechol-O-methyltransferase (COMT) inhibitor • Oral capsules: 25 mg and 50 mg • Recommended dosage is 50 mg once daily at bedtime; reduce dose to 25 mg once daily at bedtime in patients with moderate hepatic impairment (Child-Pugh B); do not consume food 1 hour before or after opicapone dose • Launch is expected in 2020

Expanded Indications ixekizumab (Taltz®) Eli Lilly

• sBLA approval 03/26/2020 • Expanded indication for the treatment of moderate to severe plaque psoriasis in pediatric patients ≥ 6 years of age who are candidates for systemic therapy or phototherapy » Previously approved in adults only with moderate to severe plaque psoriasis » Also approved for adults with active psoriatic arthritis and adults with active ankylosing spondylitis • Recommended pediatric dose is weight-based, with the starting dose ranging from 40 mg to 160 mg one time, and then every-4-week dosing thereafter ranging from 20 mg to 80 mg

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

11 | MAY 2020



Expanded Indications continued durvalumab (Imfinzi®) AstraZeneca

• sBLA approval 03/27/2020 • New indication, in combination with etoposide and either carboplatin or cisplatin, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) » Previously approved for stage III non-small cell lung cancer (NSCLC) in select adults » Also indicated for certain adults with locally advanced or metastatic urothelial carcinoma (accelerated approval) • Recommended dosage for ES-SCLC is 1,500 mg by IV infusion over 60 minutes every 3 weeks prior to etoposide and either carboplatin or cisplatin chemotherapy for 4 cycles, then every 4 weeks as a single agent; reduce dose in patients weighing ≤ 30 kg

luspatercept-aamt (Reblozyl®) Celgene

• sBLA approval 04/03/2020; Orphan Drug • New indication for adults with anemia failing an erythropoiesis stimulating agent and requiring ≥ 2 red blood cell (RBC) units over 8 weeks with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/ myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/ MPN-RS-T); not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia » Also approved for the treatment of anemia in adults with beta thalassemia who require regular RBC transfusions • Recommended starting dosage remains weight-based at 1 mg/kg once every 3 weeks by SC injection, with dose titration based on response and interruption of therapy for adverse reactions

encorafenib (Braftovi®) Array Biopharma

• sNDA approval 04/08/2020; Breakthrough Therapy, Priority Review • New indication, in combination with cetuximab, for the treatment of adults with metastatic colorectal cancer (CRC) who have received prior therapy and have a BRAF V600E mutation, as detected by an FDA-approved test; not indicated for patients with wild-type BRAF CRC » Also approved in combination with binimetinib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation as detected by an FDA-approved test; not indicated for patients with wild-type BRAF melanoma • Recommended dosage for CRC is 300 mg orally once daily with or without food

duloxetine (Cymbalta®) Eli Lilly

• sNDA approval 04/20/2020 • Expanded indication to include pediatric patients ages 13 to 17 years with fibromyalgia » Previously approved in adults only for fibromyalgia » Also approved for major depressive disorder in adults, generalized anxiety disorder in patients ≥ 7 years of age, diabetic peripheral neuropathic pain in adults, and chronic musculoskeletal pain in adults • Recommended dosage in pediatric patients with fibromyalgia is 30 mg once daily; may be increased to 60 mg once daily based on response and tolerability

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant. References:

12 | MAY 2020

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