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JULY 2020

CLINICAL

ALERT YOUR MONTHLY SOURCE FOR DRUG INFORMATION HIGHLIGHTS

EDITORIAL STAFF EDITOR IN CHIEF Maryam Tabatabai PharmD

TRENDING TOPICS

COVID-19 UPDATE

BIOSIMILAR CORNER

DRUG INFORMATION HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

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


TRENDING TOPICS HOT TOPIC: METFORMIN ER RECALLED DUE TO NDMA The United States (US) Food and Drug Administration (FDA) has informed the public and healthcare providers (HCPs) about recalls involving select lots of metformin extended-release (ER) that were found to contain levels of N-Nitrosodimethylamine (NDMA) above the acceptable intake level (> 96 ng/day) during agency testing. Metformin, a biguanide used to control hyperglycemia, is generally recommended as a 1st-line agent for most patients with type 2 diabetes mellitus (T2DM), and consequently, it is widely used. To prevent unnecessary hyperglycemia and its complications, the FDA urges patients to continue to use metformin, even following recalls, until they are able to consult with their HCP to prescribe an alternative. Five manufacturers have issued voluntary recalls of their metformin ER products due to NDMA levels exceeding the acceptable threshold. Affected lots include all lots from Apotex and Amneal, 1 lot from Marksans (labeled as Time-Cap), 1 lot from Lupin, and 14 lots from Teva (labeled as Actavis). The FDA has posted detailed information regarding the recalls on their website. The FDA does not expect NDMA, a common contaminant found in water and select foods (e.g., cured or grilled meats, dairy products, vegetables), to cause harm when ingested at low levels over a period of several years. At levels exceeding daily intake recommendations over a long time period, NDMA may increase the risk of cancer. Previously, several lots of select angiotensin II receptor blockers (ARBs) and heartburn medications (e.g., ranitidine, nizatidine) were recalled due to the same impurity. Subsequently, the FDA requested withdrawal of all ranitidine products from the market due to NDMA. To prevent further risk, the FDA has asked all manufacturers of metformin ER to test every batch of product prior to release in the US. Previously, this concern had been 2 | JULY 2020

reported in countries outside of the US, but the FDA’s testing at the time did not demonstrate levels exceeding the FDA’s acceptable daily intake limit. The FDA has reevaluated this risk following a citizen petition filed by a private laboratory and will continue to inform the public of their future findings and related voluntary recalls.

ICER EVIDENCE REPORT ON CF THERAPIES The Institute for Clinical and Economic Review (ICER) has released an evidence report on the treatments for cystic fibrosis (CF) evaluating the comparative clinical effectiveness and value of elexacaftor/tezacaftor/ivacaftor (Trikafta™). The report also provides an update of new data since the May 2018 review of ivacaftor (Kalydeco®), lumacaftor/ivacaftor (Orkambi®), and tezacaftor/ivacaftor (Symdeko®). Trikafta, Kalydeco, Orkambi, and Symdeko are all cystic fibrosis transmembrane conductance regulator (CFTR) modulators indicated for specific CF patients. Trikafta received FDA approval in October 2019 and is indicated for the treatment of CF in patients ≥ 12 years old who have at least 1 F508del mutation in the CFTR gene. About 90% of CF patients have at least 1 copy of the F508del mutation. Based on the current indication for patients ≥ 12 years of age, about 17,000 patients in the US are eligible for Trikafta. For the indicated populations, Trikafta received an “A” evidence rating corresponding with high certainty that the drug provides a substantial net health benefit over standard of care as well as over Symdeko. Patients receiving Trikafta reported significant improvement in their health after starting therapy. Improvements were noted in the patients’ coughing, the number of pulmonary events, as well as reliance on certain supportive therapies (e.g., insulin, laxatives, hypertonic saline). Furthermore, they reported being able to engage in activities (e.g., exercising, social events) that prior to starting Trikafta were not possible. ICER also concluded Trikafta was


TRENDING TOPICS continued likely to be at least as good as using Symdeko and potentially better in the unstudied subpopulation of patients who are heterozygous for the F508del mutation and a residual function mutation. The new real-world data for Kalydeco, Orkambi, and Symdeko confirmed the previously established ICER evidence ratings. Evidence demonstrates with high certainty that, compared to best supportive care, in the population of patients that each agent is indicated for use, Kalydeco has a substantial net health benefit, Orkambi carries a small net health benefit, and Symdeko has at least a small net health benefit with the potential for a substantial benefit. ICER expects most eligible patients will receive the new agent Trikafta rather than these therapies.

COVID-19: NOTABLE DEVELOPMENTS Preliminary findings from the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial have demonstrated a potential benefit from the corticosteroid dexamethasone in certain patients with severe respiratory complications from the novel coronavirus infection (COVID-19). The trial is evaluating a number of potential treatments at more than 170 hospitals in the United Kingdom. Patients were randomized to dexamethasone 6 mg once daily given orally or by intravenous (IV) injection for 10 days (n=2,104) or usual care (n=4,321). In the usual care study arm, the 28-day mortality rate was highest for those requiring ventilation (41%), followed by patients who required oxygen (25%); the lowest 28-day mortality rate was observed in patients who did not have any respiratory intervention (13%). Data demonstrated dexamethasone decreased deaths by one-third in ventilated patients (rate ratio [RR] 0.65, 95% confidence interval [CI] 0.48 to 0.88, p=0.0003) and one-fifth in patients receiving oxygen (RR 0.8, 95% CI, 0.67 to 0.96; p=0.0021); however, a benefit was not seen in patients not using respiratory support (RR 1.22, 95% CI 0.86 to 1.75; p=0.14). Due to the potential public health implications, researchers are in the process of publishing the full study findings as quickly as possible. In June 2020, the FDA revoked the emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate. This decision was

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made following determination that the criteria for the EUA was no longer met, since chloroquine and hydroxychloroquine were likely not effective for treating COVID-19 and carried the potential for serious safety issues (cardiac events, etc.). As a result, it was determined the benefits do not outweigh the risks of using these medications for the purposes provided on the previously issued EUA. Relatedly, the FDA recently issued a warning to HCPs on a new potential drug interaction for the investigational IV antiviral drug remdesivir. Based on non-clinical laboratory data, concurrent use with chloroquine or hydroxychloroquine may lead to decreased antiviral activity of remdesivir. Although the decreased antiviral activity has not been observed in the clinical setting, the FDA has updated the fact sheets for HCPs for remdesivir to warn of this potential interaction. Additional updates have been made to these fact sheets clarifying dosing and administration recommendations and adding safety information and recent clinical trial data. Corresponding updates were also made to the fact sheet for patients and caregivers. The FDA issued an EUA in May 2020 for remdesivir allowing distribution and administration by HCPs for COVID-19 in adults and pediatric patients hospitalized with severe disease; the safety and efficacy evaluations of remdesivir are ongoing. The FDA has collaborated with the National Institutes of Health (NIH) to update the CURE ID crowdsourcing application (app) to improve the ability to share information on treating COVID-19 patients who are not eligible for clinical trials. The app can be accessed from a mobile device or via the website. The FDA has also released a new website with resources for HCPs and a guidance document providing details on the impact of COVID-19 on FDA meetings, user fee application timelines, and reviews of drug and biological applications. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, the Centers for Disease Control and Prevention (CDC), the NIH, and the World Health Organization (WHO) websites. State and local health departments also provide valuable information regarding management in local communities.


BIOSIMILAR CORNER NEW NEULASTA® BIOSIMILAR

UPDATED PURPLE BOOK OF BIOLOGICS

Pegfilgrastim-apgf (Nyvepria™), a new biosimilar to reference product Neulasta® (pegfilgrastim), has received FDA approval. Pegfilgrastim-apgf is a leukocyte growth factor indicated to decrease the incidence of infection as manifested by febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. It is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. Neulasta carries an additional indication for patients with hematopoietic subsyndrome of acute radiation syndrome. Nyvepria is not interchangeable with Neulasta.

The Purple Book database has been updated to include all FDA-licensed biological products approved by the Center for Drug Evaluation and Research (CDER). This includes biologics previously approved as new drug applications (NDAs) that are now deemed to be approved under a biologics license application (BLA) under section 351 of the Public Health Service Act, which took effect in March 2020. In addition to including these transitioned biologic products (insulin, growth hormone, etc.), the 2nd iteration of the searchable Purple Book database allows for downloadable reports, including historical reports highlighting new or updated products.

Approval of pegfilgrastim-apgf was based on data demonstrating the product was highly similar to reference product Neulasta. The recommended dosing for patients with cancer receiving myelosuppressive chemotherapy is 6 mg subcutaneously (SC) once per chemotherapy cycle (not to be administered between 14 days before and 24 hours following cytotoxic chemotherapy). For pediatric patients weighing < 45 kg, weight-based dosing should be used. For pediatric patients < 10 kg, dosing is 0.1 mg/kg. Pegfilgrastim-apgf will be supplied as a 6 mg/0.6 mL solution in a single-dose prefilled syringe for manual use only. A patient or caregiver can administer after receiving training from an HCP. Unlike pegfilgrastim biosimilars, reference product Neulasta is also available co-packaged with an on-body injector. None of the biosimilars are supplied or indicated for use with this device. Pegfilgrastim-apgf is the 4th biosimilar to Neulasta to receive FDA approval. Other biosimilars to Neulasta in order of FDA approval are pegfilgrastim-jmdb (Fulphila™), pegfilgrastim-cbqv (Udenyca®), and pegfilgrastim-bmez (Ziextenzo™). Pegfilgrastim-apgf (Nyvepria) is expected to launch later in 2020 and will be available from Pfizer/ Hospira. 4 | JULY 2020

Future updates will include all FDA-licensed biologic products approved by the Center for Biologics Evaluation and Research (CBER) as well as additional enhanced features. As a result of this 2nd phase of updates, the CDER List of Licensed Biological Products will no longer be updated or available; however, the CBER List of Licensed Biological Products will continue to be updated and available until all of the CBER-regulated products are in the database. The new searchable Purple Book database provides enhanced functionality and additional transparency through its comprehensive compilation of information on biologics. The FDA’s intent is to increase public awareness about these products and provide information on biosimilars and products deemed interchangeable. The complete database will also include details regarding product exclusivity. The searchable Purple Book database can be accessed at purplebooksearch.fda.gov, and the current portable document format (PDF) list of CBER-regulated products is available separately.


DRUG INFORMATION

HIGHLIGHTS • Among the estimated 7,000 known rare diseases, < 10% have an available FDA-approved treatment. As part of their goal to build a Rare Disease Cures Accelerator, the FDA announced a request for public information and comments regarding short- and long-term objectives of a global clinical trials network, its organizational structure, investigator experience, models of governance, leverage opportunities, information required, milestones and timelines, and potential challenges. • The American Gastroenterological Association (AGA) and the Joint Task Force on Allergy-Immunology Practice Parameters issued a clinical practice guideline on the management of eosinophilic esophagitis (EoE). The group recommends topical glucocorticosteroids over no treatment. Key suggestions include the use of proton pump inhibition over no treatment in symptomatic patients and topical glucocorticosteroids over oral glucocorticosteroids. Following remission after a shortterm course of topical glucocorticosteroids, continuation of topical glucocorticosteroids is suggested over treatment discontinuation. The guideline suggests against the use of anti-immunoglobulin E (anti-IgE) therapy for EoE. Additional statements pertain to use of an elemental diet, an empiric 6-food elimination diet, an allergy testing-based elimination diet, and therapies that are only recommended in the context of a clinical trial. • The American Society of Colon and Rectal Surgeons (ASCRS) issued clinical practice guidelines for the treatment of left-sided colonic diverticulitis. Regarding medical management of acute diverticulitis, certain patients with uncomplicated diverticulitis can be treated without antibiotics, and non-operative treatment of diverticulitis can include antibiotics. Although mesalamine, rifaximin, and probiotics are not generally recommended for risk reduction for recurrent diverticulitis, these agents may reduce chronic symptoms. Interventions to possibly decrease the likelihood of diverticulitis include tobacco cessation, physical exercise, weight loss, and decreased meat intake.

• The FDA has issued a safety alert regarding certain lots of epinephrine 0.3 mg auto-injectors due to possible malfunction related to the yellow “stop collar.” Some products may not contain the yellow “stop collar,” and without this component, the device may deliver a double dose when administered. Affected products include select lots by Amneal Pharmaceuticals and Impax Laboratories. The safety alert provides detailed instructions for patients and HCPs on how to visually inspect the device to ensure the yellow “stop collar” is present. If missing, the product can be replaced for no additional cost. Notably, the products are not recalled. Due to the nature of the product, patients and caregivers should utilize the product they have on hand, with awareness of the risks. • The American College of Rheumatology (ACR) published guidelines regarding the management of gout. Strong recommendations include the use of urate-lowering therapy (ULT) for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares. ULT should be guided to a target serum urate of < 6 mg/dL. Notably, allopurinol is the preferred 1st-line agent for all patients starting ULT. The ACR strongly recommends a xanthine oxidase inhibitor over probenecid for those with moderate to severe chronic renal impairment. Initial low doses for allopurinol or febuxostat followed by titration are strongly recommended. The group strongly recommends concomitant anti-inflammatory prophylaxis for 3 to 6 months. For gout flares, colchicine, a nonsteroidal anti-inflammatory drug (NSAID), or a glucocorticoid is strongly recommended. The group also strongly recommends switching to pegloticase in those who have failed treatment with xanthine oxidase inhibitors, uricosurics, or other agents. • Acella Pharmaceuticals issued a voluntary recall of 13 lots of 30 mg, 60 mg, and 90 mg thyroid tablets, USP (NP Thyroid®) in 100-count bottles to the consumer level due to testing demonstrating superpotency (up to 115% labeled quantity of liothyronine [T3]).


PIPELINE

NEWS

UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER

FORMULATION THERAPEUTIC CLASS

PROPOSED CLINICAL USE

ANTICIPATED FDA APPROVAL

dantrolene (Ryanodex®) Eagle

• IV • muscle relaxant

Exertional heat stroke

July 9, 2020

leronlimab Cytodyn

• SC • viral entry inhibitor

Human immunodeficiency virus (HIV)-1 infection

July 10, 2020

cantharidin Verrica

• topical • blistering agent

Molluscum contagiosum

July 13, 2020

guselkumab (Tremfya®) Genentech

• IV, SC • interleukin-23 inhibitor

Psoriatic arthritis

July 13, 2020

oxymetazoline Osmotica

• ophthalmic • vasoconstrictor

Blepharoptosis

July 16, 2020

capsaicin (Qutenza®) Grünenthal

• transdermal • transient receptor potential vanilloid 1 agonist

Diabetic peripheral neuropathy

July 17, 2020

calcipotriene/betamethasone dipropionate MC2

• topical • vitamin D analog/corticosteroid

Psoriasis

July 20, 2020

sodium oxybate Jazz

• oral • central nervous system (CNS) depressant

Narcolepsy

July 21, 2020

donepezil Corium

• transdermal • acetylcholinesterase inhibitor

Alzheimer’s disease

July 30, 2020

cannabidiol (Epidiolex®) GW

• oral • cannabinoid

Tuberous sclerosis complex

July 31, 2020

fluticasone furoate/ umeclidinium bromide/ vilanterol (Trelegy Ellipta) GlaxoSmithKline

• inhaled • corticosteroid/anticholinergic/ beta2-adrenergic agonist

Asthma

July 31, 2020

triheptanoin Ultragenyx

• oral • lipid replacement therapy

Long-chain fatty acid oxidation disorders

July 31, 2020

IV = intravenous; SC = subcutaneous

6 | JULY 2020


RECENT FDA

APPROVALS DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs clobetasol propionate (Impeklo™) Mylan

• 505(b)(2) NDA approval 05/19/2020 • Indicated for the relief of inflammatory and pruritic manifestations of corticosteroidresponsive dermatoses in patients ≥ 18 years; do not use for rosacea or perioral dermatitis or in patients < 18 years due to high rates of hypothalamic-pituitaryadrenal (HPA) axis suppression • Topical corticosteroid • Lotion: 0.05% in metered-dose pump • Recommended dosage is to apply directly to affected areas twice daily for a maximum of 10 actuations per application or 20 actuations a day for a duration of 2 weeks; for moderate to severe plaque psoriasis (PsO), treatment can be extended for another 2 weeks for localized lesions without adequate improvement

apomorphine hydrochloride (Kynmobi™) Sunovion

• 505(b)(2) NDA approval 05/21/2020 • Indicated for acute, intermittent treatment of “off” episodes of Parkinson’s disease • Non-ergoline dopamine agonist • Sublingual film: 10 mg, 15 mg, 20 mg, 25 mg, 30 mg • Recommended dosage is initiated under supervision of an HCP starting at 10 mg when the patient is in an “off” state and titrated to a maximum single dose of 30 mg for a maximum of 5 doses per day; treatment with a concurrent antiemetic (e.g., trimethobenzamide) is recommended, starting 3 days prior to the 1st dose • Product availability is expected in September 2020

lactic acid, citric acid, potassium bitartrate (Phexxi™) Evofem

• 505(b)(2) NDA approval 05/22/2020 • Indicated for on-demand prevention of pregnancy in females of reproductive potential • Vaginal pH regulator contraceptive • Vaginal gel: 5 g pre-filled single-dose vaginal applicator of lactic acid (1.8%), citric acid (1%), potassium bitartrate (0.4%) • Recommended dosage is 1 applicator vaginally immediately before or up to 1 hour before each episode of vaginal intercourse • Product availability is expected in early September 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.


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued artesunate (no brand name) Amivas

solifenacin succinate (Vesicare LS™) Astellas

• 505(b)(2) NDA approval 05/26/2020; Orphan Drug, Priority Review • Indicated for initial treatment of severe malaria in adults and pediatrics; treatment of severe malaria with artesunate should be followed by a complete treatment course of an appropriate oral antimalarial regimen as it does not treat the hypnozoite liver stage forms of Plasmodium and will therefore not prevent malaria relapses due to Plasmodium vivax or Plasmodium ovale • Antimalarial • Injection: 110 mg artesunate powder in single-dose vials (SDVs) for reconstitution with the supplied diluent • Recommended dosage is 2.4 mg/kg IV as a slow bolus over 1 to 2 minutes at 0 hours, 12 hours, and 24 hours, then once daily until patient is able to tolerate oral therapy • Product availability is expected in the next few months • NDA approval 05/26/2020; Priority Review • Indicated for neurogenic detrusor overactivity in patients ≥ 2 years • Muscarinic antagonist • Oral suspension: 5 mg/5 mL • Recommended dosage is weight-based starting at 2 mL orally once daily • Product availability is expected in late 2020

minocycline hydrochloride (Zilxi™) Foamix

• 505(b)(2) NDA approval 05/28/2020 • Indicated for inflammatory lesions of rosacea in adults • Tetracycline • Topical foam: 1.5% suspension • Recommended dosage is to apply to affected areas once daily; gently rub into the skin • Product availability is expected in 4Q 2020

elagolix/estradiol/ norethindrone acetate (Oriahnn™) Abbvie

• 505(b)(2) NDA approval 05/29/2020 • Indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women; use should be limited to 24 months due to the risk of continued bone loss which may be irreversible • Combination of a gonadotropin-releasing hormone (GnRH) receptor antagonist, an estrogen, and a progestin • Oral capsules: elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg; elagolix 300 mg • Recommended dosage is 1 combination capsule in the morning and 1 elagolix capsule in the evening, not to exceed 24 months of therapy • Boxed warning for thromboembolic disorders and vascular 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 | JULY 2020


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued inebilizumab-cdon (Uplizna™) Viela Bio

• BLA approval 06/11/2020; Breakthrough Therapy, Orphan Drug • Indicated for neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive • CD19-directed cytolytic antibody • Injection: 100 mg/10 mL solution in a SDV • Recommended dosage is 300 mg, then a 300 mg dose 2 weeks after, followed by subsequent doses of 300 mg every 6 months beginning 6 months after the initial dose, each dose administered as an IV infusion

insulin glargine (Semglee™) Mylan

• 505(b)(2) NDA approval deemed to be a BLA 06/11/2020 • Indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus (T1DM) and in adults with T2DM • Long-acting human insulin analog • Injection: 100 units/mL (U-100) in 10 mL multiple-dose vial; 3 mL prefilled pen • Recommended dosage is administered once daily at any time of day via SC injection into the abdominal area, thigh, buttocks, or upper arm and is individualized

dolutegravir (Tivicay PD) ViiV

• NDA approval 06/12/2020; Priority Review • Indicated in combination with other antiretroviral (ARV) agents for HIV-1 infection in adults (treatment-naïve or -experienced) and in pediatric patients (treatment-naïve or -experienced but integrase strand transfer inhibitor [INSTI]-naïve) ≥ 4 weeks of age and weighing ≥ 3 kg • HIV-1 INSTI • Tablets for oral suspension: 5 mg; not bioequivalent or interchangeable with dolutegravir (Tivicay) tablets • Recommended dosage for pediatric patients is weight-based (5 mg to 30 mg once daily); adult dose is 50 mg once or twice daily depending on patient characteristics

insulin lispro-aabc (Lyumjev™) Lilly

• BLA approval 06/15/2020 • Indicated to improve glycemic control in adults with diabetes mellitus • Rapid-acting human insulin analog • Injection: 100 units/mL (U-100) in 10 mL multiple-dose vial, 3 mL KwikPen®, Junior KwikPen, Tempo Pen™, and cartridges; 200 units/mL (U-200) 3 mL KwikPen • Recommended dosage is individualized and administered SC or IV

lurbinectedin (Zepzelca™) Pharma Mar

• NDA approval 06/15/2020; Accelerated Approval, Orphan Drug, Priority Review, Project Orbis • Indicated for adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy; continued approval may require demonstration of benefit in confirmatory clinical trials • Alkylating agent • Injection: 4 mg of lyophilized powder in SDV for reconstitution • Recommended dosage is 3.2 mg/m2 by IV infusion over 60 minutes every 21 days • Product availability is expected in early July

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.


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

Expanded Indications brigatinib (Alunbrig®) Ariad

• sNDA approval 05/22/2020; Assessment Aid, Orphan Drug, Priority Review • Expanded indication for adults with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test » Previously indicated in patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib (Xalkori®) (Accelerated Approval) • Recommended dosage is 90 mg orally once daily for 7 days, then increase to 180 mg once daily, with or without food

dupilumab (Dupixent®) Regeneron

• sBLA approval 05/26/2020 • Expanded indication for patients ≥ 6 years with moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable » Previously only indicated for use in AD patients ≥ 12 years » Also indicated as an add-on maintenance treatment for certain patients ≥ 12 years with asthma and in certain adults with rhinosinusitis with nasal polyposis • Recommended dosage in AD for pediatric patients is SC weight-based doses

nivolumab + ipilimumab (Opdivo® + Yervoy®) Bristol-Myers Squibb

• sBLA approval 05/26/2020; Assessment Aid, Fast Track, Priority Review, Project Orbis, Real-Time Oncology Review • New indication for the 1st-line treatment of adults with metastatic or recurrent NSCLC with no epidermal growth factor receptor (EGFR) or ALK genomic tumor aberrations in combination with 2 cycles of platinum-doublet chemotherapy • Recommended dosage is nivolumab 360 mg IV every 3 weeks and ipilimumab 1 mg/kg IV every 6 weeks and histology-based, platinum-doublet chemotherapy every 3 weeks for 2 cycles, followed by nivolumab in combination with ipilimumab continued until disease progression, unacceptable toxicity, or up to 2 years

piperacillin/tazobactam (Zosyn®) Wyeth

• sNDA approval 05/26/2020 • Expanded indication for nosocomial pneumonia from 2 months of age to < 18 years » Previously only indicated for nosocomial pneumonia in adults » Also indicated in adults for female pelvic infections, community-acquired pneumonia, skin and skin structure infections, and for intra-abdominal infections in patients ≥ 2 months • Recommended dosage for nosocomial pneumonia in pediatric patients ≤ 40 kg and age 2 months to 9 months is 90 mg/kg IV every 6 hours; for pediatric patients that weigh ≤ 40 kg and age > 9 months, recommended dosing is 112.5 mg/kg IV every 6 hours; pediatric patients weighing > 40 kg should receive the adult dose

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 | JULY 2020


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

Expanded Indications continued bedaquiline (Sirturo®) Janssen

• sNDA approval 05/27/2020; Accelerated Approval • Expanded indication for patients ≥ 5 years and weighing ≥ 15 kg as part of a combination regimen for the treatment of pulmonary multi-drug resistant tuberculosis (MDR-TB); use should be reserved for when an effective treatment regimen cannot otherwise be provided; continued approval may require demonstration of benefit in confirmatory clinical trials » Already indicated for this use in adults and pediatric patients 12 to < 18 years and weighing ≥ 30 kg (Accelerated Approval) • Recommended dosage for patients ≥ 5 years and weighing ≥ 15 kg is based on body weight with patients 15 kg to < 30 kg receiving 200 mg orally once daily for weeks 1 and 2, followed by 100 mg orally three times per week for weeks 3 to 24; for patients ≥ 30 kg, 400 mg orally once daily for weeks 1 and 2, followed by 200 mg orally three times per week for weeks 3 to 24; administer tablets with food

ticagrelor (Brilinta®) AstraZeneca

• sNDA approval 05/28/2020 • New indication for the reduction of risk of 1st myocardial infarction (MI) or stroke in patients with coronary artery disease (CAD) at high risk for such events; efficacy was established in a population with T2DM » Also indicated to reduce the risk of cardiovascular (CV) death, MI, and stroke in patients with acute coronary syndrome (ACS) or a history of MI • Recommended dosage is 60 mg orally twice daily along with a daily maintenance dose of 75 to 100 mg of aspirin

bevacizumab (Avastin®) Genentech

• sBLA approval 05/29/2020 • New indication in combination with atezolizumab (Tecentriq®) for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy » Also indicated for select patients with metastatic colorectal cancer (CRC), NSCLC, recurrent glioblastoma, metastatic renal cell carcinoma (RCC), persistent/recurrent or metastatic cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer • Recommended dosage for HCC is 15 mg/kg IV after administration of 1,200 mg of atezolizumab IV on the same day every 3 weeks until disease progression or unacceptable toxicity

ixekizumab (Taltz®) Lilly

• sBLA approval 05/29/2020 • New indication for adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation » Also indicated for adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS) and patients ≥ 6 years with moderate to severe PsO who are candidates for systemic therapy or phototherapy • Recommended dosage is 80 mg by SC injection every 4 weeks

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.


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

Expanded Indications continued ramucirumab (Cyramza®) Lilly

• sBLA approval 05/29/2020; Assessment Aid • New indication for 1st-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) mutations, in combination with erlotinib (Tarceva®) » Already indicated in combination with docetaxel (Taxotere) for select patients with metastatic NSCLC with disease progression on or after platinum-based chemotherapy and for select patients with the following cancers: gastric, CRC, and HCC • Recommended dosage in combination with erlotinib for NSCLC is 10 mg/kg every 2 weeks by IV infusion continued until disease progression or unacceptable toxicity

axitinib (Inlyta®) PF Prism

• sNDA approval 06/04/2020 • Expanded indication in combination with avelumab (Bavencio®) or pembrolizumab (Keytruda®) for the 1st-line treatment of advanced RCC » Also indicated as a single agent for the treatment of advanced RCC after failure of 1 prior systemic therapy • Recommended dosage for 1st-line advanced RCC with avelumab or pembrolizumab is 5 mg orally twice daily with or without food in combination with IV avelumab (800 mg every 2 weeks) or IV pembrolizumab (200 mg every 3 weeks or 400 mg every 6 weeks) until disease progression or unacceptable toxicity; dose escalation above the initial 5 mg dose may be considered at intervals of ≥ 2 or ≥ 6 weeks when given with avelumab or pembrolizumab, respectively

imipenem/cilastatin/ relebactam (Recarbrio™) Merck

• sNDA approval 06/04/2020; Fast Track, Priority Review, Qualified Infectious Disease Product (QIDP) • New indication in adults with hospital-acquired bacterial pneumonia/ventilatorassociated bacterial pneumonia (HABP/VABP) caused by susceptible gram-negative microorganisms » Also indicated in adults who have limited or no alternative treatment options for complicated urinary tract infections (cUTI), including pyelonephritis and complicated intra-abdominal infections (cIAI) • Recommended dosage is 1.25 g by IV infusion over 30 minutes every 6 hours

nivolumab (Opdivo®) Bristol-Myers Squibb

• sBLA approval 06/10/2020; Assessment Aid, Orphan Drug, Priority Review • New indication for unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy » Also indicated for select patients with the following types of cancer: melanoma, NSCLC, SCLC, RCC, classical Hodgkin lymphoma (cHL), squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), CRC, and HCC • Recommended dosage for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks by IV infusion

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.

12 | JULY 2020


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

Expanded Indications continued etanercept-szzs (Erelzi™) Sandoz

• sBLA 06/11/2020 approval • Expanded indication to include patients ages 4 to 17 years with chronic moderate to severe PsO who are candidates for systemic therapy or phototherapy » Previously indicated for adults only with PsO » Also indicated for rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA) in patients ≥ 2 years, PsA, AS • Recommended dosage for pediatric PsO patients weighing ≥ 63 kg is 50 mg once weekly by SC injection; there is not a dosage form that allows weight-based dosing for pediatric patients < 63 kg

dolutegravir (Tivicay) ViiV

• sNDA 06/12/2020 approval; Priority Review • Expanded indication to include treatment-naïve and -experienced, INSTI-naïve patients weighing ≥ 14 kg to < 30 kg in combination with other ARV agents for the treatment of HIV-1 infection » Previously indicated in combination with other ARV agents for HIV-1 infection in adults and in pediatric patients weighing ≥ 30 kg » Also indicated in combination with rilpivirine (Edurant®) as a complete regimen for the treatment of HIV-1 infection in select adults • Recommended dosage for adults is 50 mg once or twice daily depending on patient characteristics; for pediatric patients ≥ 14 kg, the dosage is weight-based (40 mg or 50 mg once daily)

canakinumab (Ilaris®) Novartis

• sBLA 06/16/2020; Priority Review • Expanded indication to include patients with active adult-onset Still’s disease (AOSD) » Previously indicated for active systemic juvenile idiopathic arthritis (SJIA) in patients ≥ 2 years » Also indicated for various forms of periodic fever syndromes • Recommended dosage for Still’s disease (AOSD and SJIA) is 4 mg/kg (maximum of 300 mg) SC every 4 weeks for patients with a body weight ≥ 7.5 kg

gemtuzumab ozogamicin (Mylotarg™) Wyeth

• sBLA approval 06/16/2020; Priority Review • Expanded indication for newly diagnosed CD33-positive acute myeloid leukemia (AML) to include pediatric patients ≥ 1 month » Previously indicated for this use in adults only » Also indicated for relapsed or refractory CD33-positive AML in patients ≥ 2 years • Recommended dosage for pediatric patients ≥ 1 month is 3 mg/m2 for patients with body surface area (BSA) ≥ 0.6 m2 and 0.1 mg/kg for patients with BSA < 0.6 m2 given once in combination with standard chemotherapy for the 1st induction cycle and given once in combination with standard chemotherapy for the 2nd intensification cycle depending on the risks and benefits via IV infusion over 2 hours

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.


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

Expanded Indications continued pembrolizumab (Keytruda®) Merck

• sBLA 06/16/2020; Accelerated Approval, Assessment Aid, Priority Review • New indication for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) (≥ 10 mutations/megabase [mut/Mb]) solid tumors, as detected by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options; safety and efficacy in pediatric patients with TMB-H CNS cancers have not been determined; continued approval may require demonstration of benefit in confirmatory clinical trials » Also indicated for select patients with the following types of cancer: melanoma, NSCLC, SCLC, SCCHN, cHL, primary mediastinal large b-cell lymphoma (PMBCL), UC, microsatellite instability-high (MSI-H), gastric, esophageal, cervical, HCC, Merkel cell carcinoma (MCC), RCC, and endometrial carcinoma • Recommended dosage for TMB-H in adults is 200 mg every 3 weeks or 400 mg every 6 weeks, and 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics; administered as an IV infusion over 30 minutes

secukinumab (Cosentyx®) Novartis

• sBLA 06/16/2020 approval • New indication of active nr-axSpA in adults with objective signs of inflammation » Also indicated for adults with the following: moderate to severe PsO who are candidates for systemic therapy or phototherapy; active PsA, active AS • Recommended dosage for nr-axSpA can be administered with a loading dose as 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter, or without a loading dose as 150 mg every 4 weeks; administered by SC injection

burosumab-twza (Crysvita®) Ultragenyx

• sBLA 06/18/2020 • New indication for fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in patients ≥ 2 years » Also indicated for X-linked hypophosphatemia (XLH) in patients ≥ 6 months • Recommended dosage is administered SC by an HCP with pediatric TIO patients receiving 0.4 mg/kg every 2 weeks initially, and adult TIO patients receiving 0.5 mg/kg every 4 weeks initially

tazemetostat (Tazverik™) Epizyme

• NDA 06/18/2020; Accelerated Approval, Fast Track, Orphan Drug, Priority Review • New indication for adults with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment options; continued approval may require demonstration of benefit in confirmatory clinical trials » Also indicated for patients ≥ 16 years with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection (Accelerated Approval) • Recommended dosage is 800 mg orally twice daily with or without food

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:

fascrs.org

14 | JULY 2020

fda.gov

gastro.org

icer-review.org

ox.ac.uk/

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rheumatology.org

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Clinical Alert - July 2020  

Clinical Alert - July 2020  

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