MRx Clinical Alert - March 2022

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MARCH 2022










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

TRENDING TOPICS EUA — BEBTELOVIMAB FOR COVID-19 The FDA has granted an EUA to bebtelovimab, an investigational monoclonal antibody (mAb) from Eli Lilly. It is authorized for emergency use for the treatment of mildto-moderate COVID-19 in adults and pediatric patients (≥ 12 years old weighing ≥ 40 kg) with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative approved or authorized COVID-19 treatment options are not accessible or clinically appropriate. It is not authorized for use in patients who are hospitalized or who, due to COVID-19, require oxygen therapy/respiratory support or an increase in baseline respiratory support. It is also not authorized for mild-tomoderate COVID-19 in regions where infection is likely to have been caused by a non-susceptible variant. Bebtelovimab is supplied as a solution in an SDV (175 mg/2 mL) with administration as a single 175 mg dose via IV injection as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset. Patients should be monitored during administration for infusion-related reactions and for ≥ 1 hour following completion of the injection. Bebtelovimab binds to the spike protein of SARS-CoV-2, blocking its attachment to the human ACE2 receptor; laboratory data has shown that it is active against the Omicron variant and BA.2 Omicron subvariant. The EUA is based on data from the randomized, phase 1/2 BLAZE-4 clinical study evaluating bebtelovimab alone and in combination with other mAbs for mild-to-moderate COVID-19. The trial included a low-risk subject portion that was placebo-controlled and open-label portions in high-risk subjects. Generally, the rate of COVID-19related hospitalization and death through day 29 was lower for those who received bebtelovimab alone or with other mAbs than that seen with placebo in past trials of other mAbs in high-risk patients. However, the data should be interpreted with caution due to differences in circulating variants and patient risk factors. The most common adverse effects were infusion-related reactions (0.3%), pruritus (0.3%), and rash (0.8%). 2 | MARCH 2022

BEHAVIORAL HEALTH CORNER: 2020 SURVEY Results from the 2020 National Survey on Drug Use and Health (NSDUH) by SAMHSA have been released. Overall, an estimated 52.9 million US adults (21%) were found to have any mental illness (e.g., mental, behavioral, or emotional disorder) with females affected more than males (25.8% versus 15.8%). The prevalence was highest among young adults 18 to 25 years old (30.6%), followed by adults 26 to 49 years old (25.3%); adults ≥ 50 years old had the lowest rates (14.5%). Prevalence of any mental illness was greatest for adults identifying as ≥ 2 races (35.8%) and lowest for Asian adults (13.9%); the prevalence for White adults was 22.6%. Additional details are provided on use of mental health services, prevalence of serious mental illness, and mental disorders in adolescents.

COVID-19: NOTABLE DEVELOPMENTS The FDA has revised the EUA for sotrovimab to clarify it is not authorized for use in geographic areas where infection is likely to have been caused by a variant that is not susceptible to the agent. The previously scheduled VRBPAC meeting evaluating the EUA request for use of the Pfizer-Biontech COVID-19 vaccine in children 6 months to 4 years old has been postponed following new data provided by Pfizer. These data are from an ongoing clinical trial, and the FDA has stated that an update will be provided on rescheduling the meeting after receipt and evaluation of third dose data for this age group. The CDC has endorsed the ACIPs’ recommendation regarding use of the FDA-approved Moderna COVID-19 vaccine (Spikevax™) in adults ≥ 18 years old. The CDC has published an MMWR on the effectiveness of a third dose of either mRNA vaccine in preventing COVID-19 hospitalization in adults; compared with receipt of 2 mRNA COVID-19 vaccine doses, receiving a third dose (booster dose) increased vaccine effectiveness for prevention of hospitalization for immunocompetent adults from 82% to 97% and for immunocompromised adults from 69% to 88%. The FDA has updated the Q&A webpages for both FDA-approved COVID-19 vaccines: Spikevax and Comirnaty®. Please refer to the COVID-19 disclaimer at the end of the publication.


HAPPENINGS & HIGHLIGHTS • For the week ending February 19, 2022, the CDC reported that influenza activity continues to be sporadic across the US, with increasing activity in some areas. No jurisdictions report very high or high influenza-like illness (ILI) activity, 2 moderate, 3 low, 48 minimal, and 2 with insufficient data. As of February 8, 2022, no current shortages are being reported for antiviral medications. • The FDA has approved the first generic to Allergan’s Restasis® (cyclosporine ophthalmic emulsion, 0.05%) from Mylan. It is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca (also known as dry eye). • In October 2021, Oncopeptides announced withdrawal of Pepaxto® (melphalan flufenamide) based on overall survival data (HR, 1.104 versus pomalidomide) from the phase 3 OCEAN study. However, in January, the company rescinded the withdrawal after further analysis of OCEAN data and other trial data. Use in the US is currently on hold, but Oncopeptides will discuss the new data with the FDA. Pepaxto received Accelerated Approval in combination with dexamethasone for adults with R/R multiple myeloma who have received ≥ 4 prior lines of therapy and whose disease is refractory to ≥ 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed mAb.

• GSK has received approval for a new 40 mg/0.4 mL liquid formulation of mepolizumab (Nucala®) packaged in a safety syringe device for use in children 6 to 11 years old as add-on maintenance treatment for severe eosinophilic asthma. The new formulation allows mepolizumab to be administered to children 6 to 11 years old by a caregiver. • The FDA is investigating a possible increased risk of death with umbralisib (Ukoniq™) based on data from the UNITY trial in patients with chronic lymphocytic leukemia (CLL), an unapproved clinical use. Data revealed a possible increased risk for death in patients treated with a combination of umbralisib and an anti-CD20 mAb drug compared to those treated with standard therapy. Umbralisib received Accelerated Approval for use in certain adults with R/R marginal zone lymphoma or follicular lymphoma. HCPs should evaluate patient progress and discuss risks versus benefits of umbralisib with patients. • Gilead announced the voluntary withdrawal of idelalisib’s (Zydelig®) indications for relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic leukemia. These uses were approved under an Accelerated Approval based on objective response rates of 54% and 58%, respectively. The decision to withdraw these uses is based on difficulty enrolling patients in the confirmatory trial. Idelalisib’s indication for relapsed CLL will remain.

DRUG INFORMATION HAPPENINGS • The American Heart Association (AHA) has released a presidential advisory on Penicillin Reactions in Patients with Severe Rheumatic Heart Disease. • The CDC has published an MMWR on updated recommendations from the ACIP on use of the 15-valent pneumococcal conjugate vaccine (PCV) and 20-valent PCV in the US. • The Institute for Clinical and Economic Review (ICER) has released a final evidence report on the effectiveness and value of tirzepatide (investigational; Eli Lilly) for the treatment of type 2 diabetes. • The US Preventive Services Task Force (USPSTF) has published a final recommendation statement on screening for atrial fibrillation; for asymptomatic adults ≥ 50 years old, current evidence is inadequate to evaluate the benefits versus harms of screening for atrial fibrillation (Grade I: insufficient).







donepezil Corium

• Transdermal • Acetylcholinesterase inhibitor

Alzheimer’s disease (mild to severe)


ganaxolone Marinus

• IV, Oral • GABA receptor agonist

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorderrelated seizures


relatlimab/nivolumab Bristol-Myers Squibb

• IV • Anti-lymphocyte activation gene-3 (LAG-3) inhibitor/ Programmed cell death 1 (PD-1) inhibitor

Melanoma (unresectable or metastatic, ages ≥ 12 years)


udenafil Dong-A Socio/Allergan

• Oral • Phosphodiesterase 5 (PDE5) inhibitor

Single ventricle heart disease after Fontan palliation


vadadustat Akebia/Otsuka

• Oral • Hypoxia-inducible factor (HIF) stabilizer

Anemia due to chronic kidney disease (dialysis-dependent, dialysis-independent)


benegrastim Evive

• SC • Colony stimulating factor (CSF)



dexmedetomidine Bioxcel

• SL • Selective α2-adrenoreceptor agonist sedative

Bipolar disorder-related acute agitation; Schizophreniarelated acute agitation


4 | MARCH 2022




New Drugs faricimab-svoa (Vabysmo™) Genentech

• BLA approval 01/28/2022 • Indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME) • Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitor • Injection: 120 mg/mL solution in an SDV • Recommended dosage is administered by intravitreal injection by a qualified physician (prescribing information describes dosage and administration details) » nAMD: 6 mg/0.05 mL every 4 weeks for the first 4 doses; may be repeated every 2, 3, or 4 months based on optical coherence tomography and visual acuity evaluations » DME: 6 mg/0.05 mL every 4 weeks for ≥ 4 doses; subsequent treatment may be extended or reduced with a range of 1 to 2 months between doses based on the central subfield thickness of the macula as measured by optical coherence tomography; 6 monthly loading doses followed by treatment every 2 months is an alternative dosing regimen

baclofen oral suspension (Fleqsuvy™) Azurity

• 505(b)(2) NDA approval 02/04/2022; Standard Review • Indicated for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity, and may also be of some value in patients with spinal cord injuries and other spinal cord diseases • Not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders • GABA-ergic agonist • Oral suspension: 25 mg/5 mL • Recommended dosage is 5 mg three times daily; dose may be increased in 5 mg increments every 3 days based on clinical response and tolerability to a maximum dose of 80 mg/day (20 mg four times a day); to discontinue, slowly decrease the dosage to minimize adverse effects



New Drugs continued sutimlimab-jome (Enjaymo™) Bioverativ/Sanofi

• BLA approval 02/04/2022; Breakthrough Therapy, Orphan Drug, Priority Review • Indicated to decrease the need for red blood cell transfusion due to hemolysis in adults with cold agglutinin disease (CAD) • Complement inhibitor • Injection: 1,100 mg/22 mL (50 mg/mL) solution in an SDV • Recommended dosage is weight-based administered as an IV infusion by an HCP over 1 to 2 hours (depending on the patient’s body weight) weekly for 2 weeks then every 2 weeks thereafter » 39 kg to < 75 kg: 6,500 mg » ≥ 75 kg: 7,500 mg

mitapivat (Pyrukynd®) Agios

• NDA approval 02/17/2022; Fast Track, Orphan Drug, Priority Review • Indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency • Pyruvate kinase activator • Oral tablet: 5 mg, 20 mg, 50 mg • Recommended starting dosage is 5 mg twice daily; titrate from 5 mg twice daily to 20 mg twice daily, and then increase to the maximum dose of 50 mg twice daily with dose increases made every 4 weeks; evaluate hemoglobin (Hb) and transfusion requirement prior to increasing to the next dose level; some patients may achieve normal Hb at 5 mg twice daily or 20 mg twice daily; discontinue therapy if no benefit is seen by 24 weeks, based on Hb and hemolysis results, as well as transfusion requirements

505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant. Glossary: ACE2 angiotensin-converting enzyme 2 ACIP Advisory Committee on Immunization Practices BLA Biologics License Application CDC Centers for Disease Control and Prevention

FDA Food and Drug Administration

NDA New Drug Application

SC subcutaneous

GABA gamma-aminobutyric acid

NIH National Institutes of Health

SDV single-dose vial

GSK GlaxoSmithKline

Q&A question & answer

SL sublingual

HCP healthcare professional

R/R relapsed or refractory

US United States

HR hazard ratio

SAMHSA Substance Abuse and Mental Health Services Administration

VRBPAC Vaccines and Related Biological Products Advisory Committee

SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

WHO World Health Organization

IV intravenous

COVID-19 Coronavirus Disease 2019

MMWR Morbidity and Mortality Weekly Report

EUA Emergency Use Authorization

mRNA messenger ribonucleic acid


COVID-19 Disclaimer: 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. 6 | MARCH 2022

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