MRx Clinical Alert - November 2021

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DEPUTY EDITORS Jessica Czechowski PharmD Lara Frick PharmD, BCPS, BCPP Carole Kerzic RPh Leslie Pittman PharmD


TRENDING TOPICS DRUG FOR ANCA-ASSOCIATED VASCULITIS The US FDA has approved ChemoCentryx’s avacopan (Tavneos™) as an adjunctive therapy for adults with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]), in combination with standard therapy including glucocorticoids; it does not eliminate the need for glucocorticoid use. Avacopan is the first oral complement 5a receptor (C5aR) inhibitor and blocks C5a-mediated neutrophil activation. It is supplied as 10 mg oral capsules with a recommended dosage of 30 mg twice daily with food. ANCA-associated vasculitis (AAV), a systemic autoimmune disorder, is characterized by inflammation and the destruction of small blood vessels by neutrophils. GPA and MPA are considered the two primary forms of ANCA vasculitis. Organs affected can include the kidneys, gastrointestinal tract, lungs, and skin. Therapies include immunosuppressants such as glucocorticoids, cyclophosphamide, and rituximab (Rituxan®, biosimilars). A phase 3, randomized, double-blind, active-controlled, 52-week clinical trial (ADVOCATE) of patients with newly diagnosed or relapsed AAV (n=330) evaluated the efficacy and safety of avacopan 30 mg twice daily for 52 weeks compared to prednisone tapered, 60 mg/day to 0, over 20 weeks. At week 26, remission was achieved in 72.3% of avacopan patients and 70.1% of prednisone patients (95% confidence interval [CI], -6 to 12.8; p<0.001 for noninferiority; p=0.24 for superiority). At week 52, avacopan demonstrated superiority to prednisone for sustained remission (65.7% versus 54.9%, 95% CI, 2.6 to 22.3; p<0.001 for noninferiority; p=0.007 for superiority). Avacopan carries warnings/precautions for hepatotoxicity, hypersensitivity reactions, hepatitis B virus reactivation, and serious infections.


The FDA has amended the EUAs for COVID-19 vaccines to include booster doses following VRBPAC’s recommendations. A single booster of Moderna’s COVID-19 vaccine ≥ 6 months after the primary series is allowed for the following populations: age ≥ 65 years 2 | NOVEMBER 2021

old, age 18 to 64 years old who are at high risk of severe COVID-19, and age 18 to 64 years old with frequent institutional or occupational exposure to SARS-CoV-2. A single booster of the Janssen COVID-19 vaccine is allowed for adults ≥ 18 years old ≥ 2 months after initial vaccination with the single-dose vaccine. Additionally, the available COVID-19 vaccines can be used as a “mix and match” booster dose in eligible individuals after completing primary vaccination with a different available COVID-19 vaccine. Furthermore, the FDA clarified that a single booster dose of the Pfizer-Biontech COVID-19 vaccine can be administered ≥ 6 months after completion of the primary series to individuals 18 to 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2. The CDC has endorsed ACIPs’ recommendations which align with the FDA’s amendments. Following the FDA’s VRBPAC recommendation, the FDA authorized emergency use of the Pfizer-Biontech COVID-19 vaccine for the prevention of COVID-19 in children 5 to 11 years old given as two 10 mcg doses administered 21 days apart. This dose is one-third of the adolescent/adult dose and demonstrated safety and a significant immune response in 2,268 children. The CDC has endorsed ACIPs’ recommendation on the EUA age expansion. Merck and Ridgeback have announced the submission of an EUA for molnupiravir, an oral antiviral drug, for the treatment of mild-to-moderate COVID-19 in at-risk adults. The interim analysis of the phase 3 MOVe-OUT clinical study demonstrated an approximately 50% reduction in hospitalization or death through day 29 with molnupiravir versus placebo (7.3% versus 14.1%, respectively, p=0.0012). The FDA’s AMDAC will convene to discuss the EUA request on November 30, 2021. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, CDC, NIH, NIH guidelines, and WHO websites. State and local health departments also provide valuable information regarding management in local communities. As the COVID-19 landscape is fluid, assumptions are subject to change.


HAPPENINGS & HIGHLIGHTS • Lupin is voluntarily recalling all batches of irbesartan tablets, USP in the strengths of 75 mg, 150 mg, and 300 mg, as well as irbesartan/hydrochlorothiazide tablets, USP in the strengths of 150 mg/12.5 mg and 300 mg/12.5 mg to the consumer level due to the N-nitrosoirbesartan impurity (a probable human carcinogen). • Lilly is voluntarily recalling lot D239382D (expiration April 2022) of Glucagon® Emergency Kit for Low Blood Sugar (glucagon for injection, 1 mg per vial; diluent for glucagon, 1 mL syringe; NDC 00002-8031-01), to the consumer/user level. This lot is being recalled due to a product complaint that the vial of glucagon was in liquid form instead of the powder form; the liquid form may not reverse severe low blood sugar due to loss of potency, leading to adverse health events. • The FDA granted regular approval to pembrolizumab (Keytruda®) as a single agent for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1, as determined by an FDA-approved test; previously, this was an Accelerated Approval. Dosing for this indication is 200 mg every 3 weeks or 400 mg every 6 weeks IV over 30 minutes.

• Bayer is voluntarily recalling all unexpired Lotrimin® AF (miconazole nitrate) and Tinactin® (tolnaftate) spray products with lot numbers starting with TN, CV, or NAA, distributed between September 2018 to September 2021, to the consumer level. The recall is due to the presence of benzene in some samples. The recall is precautionary as the levels found are not anticipated to result in adverse health consequences; however, benzene is a carcinogen and, depending on level and length of exposure, can lead to blood cancers or disorders. • Roche has voluntarily withdrawn atezolizumab’s (Tecentriq®) indication for use in combination with paclitaxel protein-bound (Abraxane®) for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1, as determined by an FDA-approved test. Atezolizumab received Accelerated Approval for this use in March 2019. The postmarketing requirement, IMpassion131 study, did not achieve the primary endpoint of PFS in the first-line setting, and the FDA does not consider this indication currently appropriate due to recent developments in this treatment setting.

DRUG INFORMATION HAPPENINGS • The AASLD has published updated practice guidance for the diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome, replacing the 2012 guidelines. • The ICER has published a final evidence report on the comparative clinical effectiveness and value of eculizumab (Soliris®) and efgartigimod (investigational) for the treatment of generalized myasthenia gravis. • The USPSTF has issued final recommendations on aspirin for preventing preeclampsia and recommends lowdose aspirin (81 mg/day) after 12 weeks gestation as prevention in those who are at high risk for preeclampsia (Grade B). • The USPSTF has issued final recommendations for chlamydia and gonorrhea and recommends screening for both in all sexually active women ≤ 24 years old and in women ≥ 25 years old who are at increased risk (Grade B for both infections).







ropeginterferon alfa-2b Pharmaessentia

• SC • Pegylated interferon

Polycythemia vera


maribavir Takeda

• Oral • Benzimidazole riboside

Cytomegalovirus infection treatment (post solid organ or hematopoietic cell transplant)


omidenepag isopropyl Santen

• Ophthalmic • Selective EP2 receptor agonist

Glaucoma/ocular hypertension


vosoritide Biomarin

• SC • Natriuretic peptide



bevacizumab (biosimilar to Genentech’s Avastin®) Bio-Thera

• IV • Vascular endothelial growth factor (VEGF) inhibitor

Brain cancer; Cervical cancer; Colorectal cancer; Non-small cell lung cancer; Ovarian cancer; Renal cell carcinoma


sodium thiosulfate Fennec

• IV • Chelating agent

Chemotherapy-induced ototoxicity prevention


ciltacabtagene autoleucel Janssen/Legend

• IV • Chimeric antigen receptor T-cell immunotherapy

Multiple myeloma (relapsed or refractory)


episalvan Amryt

• Topical • Keratinocyte activator

Epidermolysis bullosa


pacritinib CTI

• Oral • Janus kinase inhibitor



plinabulin Beyondspring

• IV • Mitotic inhibitor

Chemotherapy-induced neutropenia prevention


trivalent hepatitis B vaccine VBI Vaccines

• IM • Hepatitis B vaccine

Hepatitis B infection prevention


4 | NOVEMBER 2021




New Drugs adalimumab-adbm (Cyltezo®) Boehringer Ingelheim

• sBLA 10/15/2021; interchangeable biosimilar to adalimumab (Humira®); an interchangeable biosimilar product may be substituted for the reference product without the intervention of the prescriber, at the pharmacy, depending on state pharmacy substitution laws • Indicated for certain patients with the following conditions: adults with moderately to severely active rheumatoid arthritis, moderately to severely active juvenile idiopathic arthritis in patients ≥ 2 years old, adults with active psoriatic arthritis, adults with active ankylosing spondylitis, moderately to severely active Crohn’s disease in patients ≥ 6 years old, adults with moderately to severely active ulcerative colitis (effectiveness has not been established in patients who have lost response/were intolerant to TNF blockers), and adults with moderate to severe chronic plaque psoriasis • TNF blocker • Injection: 40 mg/0.8 mL and 20 mg/0.4 mL in single-dose prefilled glass syringes • Recommended dosage is based on patient’s condition, age, and/or body weight given by SC injection under the guidance of a physician; following proper training in injection technique, patients or caregivers may administer if determined appropriate by an HCP and with follow-up, as needed • Boxed warning for serious infections and malignancy • Product availability is expected in July 2023

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.



New Drugs continued celecoxib/tramadol HCl (Seglentis®) Esteve

• 505(b)(2) NDA approval 10/15/2021; Standard Review • Indicated for the management of acute pain in adults that is severe enough to require an opioid analgesic and for which alternative treatments are inadequate • Due to the risks of addiction, abuse, and misuse with opioids, even at recommended doses, use should be reserved for patients in whom alternative treatment options (non-opioid analgesics) have not been or are not expected to be tolerated or provide adequate analgesia • NSAID/opioid agonist combination • Oral tablet: 56 mg celecoxib/44 mg tramadol HCl • Recommended dosage is to initiate with 2 tablets every 12 hours as needed for pain relief considering the patient’s pain severity, response, past analgesic experience, and risk for addiction, abuse, and misuse; use for the shortest duration consistent with individual treatment goals and discuss availability and need for access to naloxone; patients should be closely monitored for respiratory depression, particularly during the first 24 to 72 hours of starting therapy, and therapy should not be discontinued abruptly in a physically dependent patient • Boxed warnings for addiction, abuse, and misuse; opioid analgesic REMS; lifethreatening respiratory depression; accidental ingestion; CV thrombotic events; GI bleeding, ulceration, and perforation; ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children; neonatal opioid withdrawal syndrome; interactions with drugs affecting cytochrome P450 isoenzymes; risks from concurrent use with benzodiazepines or other CNS depressants • Product availability is expected in early 2022

naloxone HCl (Zimhi™) Adamis

• 505(b)(2) NDA 10/15/2021; Standard Review • Indicated in adult and pediatric patients for the emergency treatment of known or suspected opioid overdose as manifested by respiratory and/or CNS depression; intended for immediate administration as emergency therapy in settings where opioids may be present; not a substitute for emergency medical care • Injection: 5 mg/0.5 mL solution in a single-dose prefilled syringe • Recommended dosage is to administer as quickly as possible to adults or pediatric patients IM or SC into the anterolateral part of the thigh (through clothing, if needed); prolonged respiratory depression can lead to CNS damage or death; intended for administration by those ≥ 12 years of age; emergency medical care should be received immediately after use and continue to observe the patient until emergency services arrive; if the desired response is not achieved after 2 or 3 minutes, or if the patient does not respond, additional doses may be administered every 2 to 3 minutes until emergency medical assistance arrives • Product availability is expected in 1Q 2022

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.

6 | NOVEMBER 2021



New Drugs continued varenicline (Tyrvaya™) Oyster Point

• • • • •

ranibizumab (Susvimo™) Genentech

• BLA approval 10/22/2021 • Indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD) in patients who have previously responded to ≥ 2 intravitreal injections of a VEGF inhibitor • VEGF inhibitor • Injection: 100 mg/mL solution in a SDV for intravitreal use with the Susvimo ocular implant; do not substitute Susvimo with other ranibizumab products • Recommended dosage is 2 mg (0.02 mL of 100 mg/mL solution) continuously delivered via the Susvimo implant with refills every 24 weeks; supplemental treatment with 0.5 mg intravitreal ranibizumab injection may be administered in the affected eye if needed; the initial fill and ocular implant insertion and removal procedures are required to be performed under aseptic conditions by a physician experienced in vitreoretinal surgery, and the refill-exchange procedures are required to be performed under aseptic conditions by a physician experienced in ophthalmic surgery • Boxed warning for endophthalmitis with a 3-fold higher rate of occurrence compared to monthly ranibizumab intravitreal injections • Product availability is expected within months of approval

triamcinolone acetonide (Xipere™) Clearside Biomedical

505(b)(2) NDA approval 10/15/2021; Standard Review Indicated for the treatment of signs and symptoms of dry eye disease Cholinergic agonist Nasal spray solution: 0.03 mg/0.05 mL spray (60 sprays per bottle) Recommended dosage is 1 spray in each nostril twice daily (approximately 12 hours apart)

• • • • •

505(b)(2) NDA approval 10/22/2021; Standard Review Indicated for the treatment of macular edema associated with uveitis Corticosteroid Injectable suspension: 40 mg/mL in a SDV Recommended dosage is 4 mg (0.1 mL) administered as a suprachoroidal injection using the SCS Microinjector® syringe by a trained HCP; injection should take place under aseptic conditions with adequate anesthesia and a broad-spectrum microbicide applied to the periocular skin, eyelid, and ocular surface before the suprachoroidal injection; after the injection, patients should be monitored for increased intraocular pressure (via perfusion of the optic nerve head or tonometry) • Product availability is expected in 1Q 2022

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.

7 | NOVEMBER 2021

Glossary: AASLD American Association for the Study of Liver Diseases

CV cardiovascular

NIH National Institutes of Health

SDV single-dose vial

ACIP Advisory Committee on Immunization Practices

EUA Emergency Use Authorization

NSAID nonsteroidal antiinflammatory drug

TNF tumor necrosis factor

FDA Food and Drug Administration

PD-L1 programmed death-ligand 1

USPSTF US Preventive Services Task Force

GI gastrointestinal

AMDAC Antimicrobial Drugs Advisory Committee CDC Centers for Disease Control and Prevention CNS central nervous system COVID-19 Coronavirus Disease 2019


8 | NOVEMBER 2021

PFS progression-free survival

HCl hydrochloride

HCP healthcare professional ICER Institute for Clinical and Economic Review IM intramuscular IV intravenous

REMS Risk Evaluation and Mitigation Strategy SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 SC subcutaneous

© 2021, Magellan Health. All rights reserved.

US United States

VRBPAC Vaccines and Related Biological Products Advisory Committee WHO World Health Organization

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