MRx Clinical Alert - March 2021

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MARCH 2021








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


TRENDING TOPICS COVID-19: NOTABLE DEVELOPMENTS The United States (US) Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for Janssen’s single-dose coronavirus disease 2019 (COVID-19) vaccine. The EUA included interim data from the phase 3 ENSEMBLE study demonstrating 66.1% efficacy overall for prevention of moderate to severe COVID-19 at 28 days following vaccination and 72% efficacy in the US. Additionally, interim analysis showed 85.4% efficacy in prevention of severe disease and complete protection from COVID-19 related hospitalization and death by day 28. The FDA authorized the investigational vaccine for active immunization to prevent COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals ≥ 18 years old. The vaccine utilizes a recombinant adenovirus type 26 vector and is a refrigerated (2°C to 8°C) suspension in a multi-dose vial for administration as a single 0.5 mL intramuscular (IM) injection. Authorization occurred following the February 26, 2021 meeting of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) review of the vaccine. Additionally, the FDA has issued an EUA for Lilly’s bamlanivimab and etesevimab, when used in combination, for the treatment of mild to moderate COVID-19 in adults and pediatric patients (≥ 12 years old weighing ≥ 40 kg) who test positive for SARS-CoV-2 and are at a high risk for progressing to severe COVID-19. These agents should not be used in patients who are hospitalized, require oxygen, or require an increase in baseline oxygen flow rate due to COVID-19. Both agents are neutralizing immunoglobulin G1 (IgG1) monoclonal antibodies that bind to distinct epitopes on the receptor binding domain of the SARS-CoV-2 spike protein. Both are supplied as 700 mg/20 mL sterile injections for dilution and subsequent intravenous (IV) infusion consisting of 700 mg of bamlanivimab 2 | MARCH 2021

and 1,400 mg of etesevimab. A single infusion should be administered as soon as possible following the positive viral test and within 10 days of symptom onset. Bamlanivimab monotherapy previously received an EUA for select patients with COVID-19 in November 2020. Etesevimab is only authorized for use with bamlanivimab. The EUA for the combination is based on data from the phase 2/3 BLAZE-1 and phase 2 BLAZE-4, ongoing, randomized, double-blind, placebocontrolled clinical trials. On February 10, 2021, the Advisory Committee on Immunization Practices (ACIP) issued updated interim recommendations regarding the use of the authorized messenger RNA (mRNA) COVID-19 vaccines from Pfizer-BioNTech and Moderna. The changes include updated recommendations for managing, preventing, and reporting administration errors; clarification on contraindications and precautions; information on injection-site reactions; tuberculosis testing; and quarantine recommendations. Following exposure to someone with COVID-19, fully vaccinated individuals are not required to quarantine. The Centers for Disease Control and Prevention (CDC) announced 21 retail pharmacy partners in The Federal Retail Pharmacy Program for COVID-19 Vaccination, a collaboration between the federal government, pharmacies, and local governments aimed to increase COVID-19 vaccination access. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, the CDC, the Infectious Diseases Society of America (IDSA) guidelines, the National Institutes of Health (NIH), the NIH guidelines, and World Health Organization (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 • The FDA issued a Drug Safety Communication to alert the public and healthcare providers (HCPs) about preliminary results from a safety clinical study that showed an increased risk of serious heart-related problems and cancer with Pfizer’s tofacitinib (Xeljanz®, Xeljanz XR®). HCPs should consider the risks and benefits when deciding to prescribe or continue treatment with tofacitinib. Patients should be instructed not to discontinue tofacitinib treatment without first discussing these concerns with their HCP. In February 2019 and July 2019, the FDA issued a Drug Safety Communication and subsequent Boxed Warning, respectively. Both warned of an increased risk of blood clots and death associated with a 10 mg twice daily dose for the treatment of rheumatoid arthritis (RA). This dose is only approved for the treatment of ulcerative colitis (UC). The agency is working with the manufacturer to obtain and evaluate additional data and will communicate their final conclusions as soon as there is more information available.

• For the week ending February 20, 2021, the CDC is reporting influenza activity in the US continues to be lower than usual for this time of year. All jurisdictions with sufficient data reported minimal influenza-like illness (ILI); however, these data could be impacted by COVID-19 and should be interpreted carefully. • Apotex issued a voluntary recall of 2 lots of enoxaparin sodium injection, USP to the consumer level due to a packaging error resulting in incorrect syringe barrel markings. Barrel markings of 150 mg/mL (corresponding to the 120 mg/0.8 mL strength) were inadvertently used for packaging instead of 100 mg/mL markings (corresponding to the 100 mg/mL strength), and vice versa, leading to either too high or too low of an enoxaparin dose on administration. This could lead to episodes of bleeding or clotting, respectively. To date, no reports of adverse events related to use of these 2 lots have been reported.

DRUG INFORMATION HAPPENINGS • The CDC has published a Morbidity and Mortality Weekly Report (MMWR) detailing methods to enhance the fit of cloth and medical masks in order to decrease SARS-CoV-2 exposure. • The FDA has published an alert for HCPs and compounders on the risks associated with compounding of remdesivir (Veklury®), and cautions against compounding remdesivir. Furthermore, the FDA recommends the FDA-approved drug be used in patients who are prescribed remdesivir. • The FDA has released a summary of vaccine safety surveillance being instituted for COVID-19 vaccines. • The US Preventive Services Task Force (USPSTF) issued a final recommendation statement regarding interventions for tobacco smoking cessation in adults, including pregnant patients. They recommend that all adults are questioned regarding tobacco use, advised to stop using tobacco, and receive behavioral interventions for cessation (Grade A). Non-pregnant adults should also be provided FDA-approved pharmacotherapy for tobacco cessation (Grade A; insufficient evidence for assessment in pregnant patients). Evidence is also insufficient to provide recommendations regarding the use of electronic cigarettes.







tanezumab Pfizer/Eli Lilly

• IV, SC • Anti-nerve growth factor (NGF) antibody

Osteoarthritis pain

Mar-Jun 2021

axicabtagene ciloleucel (Yescarta®) Gilead

• IV • Chimeric antigen receptor T cell (CAR T) immunotherapy

Follicular lymphoma (R/R)


ropeginterferon alfa-2b Pharmaessentia

• SC • Pegylated interferon

Polycythemia vera


ponesimod Janssen

• Oral • Sphingosine 1-phosphate receptor modulator

Multiple sclerosis (relapsing)


rilonacept (Arcalyst®) Regeneron

• SC • Interleukin-1 (IL-1) antagonist

Pericarditis (recurrent)


roxadustat AstraZeneca

• Oral • Hypoxia-inducible factorstabilizer

Chronic renal failureassociated anemia (dialysisdependent/independent)


idecabtagene vicleucel Bristol-Myers Squibb/ Bluebird Bio

• IV • CAR T immunotherapy

Multiple myeloma (after 3+ prior therapies)


dasiglucagon Zealand

• SC • Glucagon analog

Hypoglycemia (diabetesrelated)


tivozanib hydrochloride monohydrate Aveo

• Oral • Vascular endothelial growth factor (VEGF) receptor inhibitor

Renal cell cancer


IV = intravenous; SC = subcutaneous; R/R=relapsed/refractory

4 | MARCH 2021

Marginal zone lymphoma (R/R)




New Drugs tepotinib hydrochloride (Tepmetko®) EMD Serono

• NDA approval 02/03/2021; Accelerated Approval, Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review, Project Orbis, Real-Time Oncology Review (RTOR) • Indicated for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal epithelial transition (MET) exon 14 skipping alterations; select patients for treatment based on the presence of MET exon 14 skipping alterations; however, a test to detect MET exon 14 skipping alterations in NSCLC is not available; continued approval may require demonstration of benefit in confirmatory clinical trials • MET kinase inhibitor • Tablets: 225 mg • Recommended dosage is 450 mg orally once daily at approximately the same time each day with food until disease progression or unacceptable toxicity

lisocabtagene maraleucel (Breyanzi®) Juno Therapeutics

• BLA approval 02/05/2021; Breakthrough Therapy, Orphan Drug, Regenerative Medicine Advanced Therapy (RMAT) • Indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma after ≥ 2 lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), highgrade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B • Not indicated for the treatment of patients with primary central nervous system lymphoma • CD19-directed genetically modified autologous T cell immunotherapy • Cell suspension for infusion with each mL containing 1.5 × 106 to 70 × 106 chimeric antigen receptor (CAR)-positive viable T cells (consisting 1:1 of the CD8 and CD4 components) with each component supplied separately in 1 to 4 single-dose 5 mL vials • Recommended dosage is a single IV autologous dose containing 50 to 110 × 106 CAR-positive viable T cells (consisting of CD8 and CD4 components) administered in a certified healthcare facility • Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicities • Available only through a Risk Evaluation and Mitigation Strategy (REMS) program

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 umbralisib tosylate (Ukoniq™) TG Therapeutics

• NDA approval 02/05/2021; Accelerated Approval, Assessment Aid, Orphan Drug (marginal zone lymphoma [MZL], follicular lymphoma [FL]), Priority Review (MZL) • Indicated for the treatment of adults with 1) relapsed or refractory MZL who have received ≥ 1 prior anti-CD20-based regimen; and 2) relapsed or refractory FL who have received ≥ 3 prior lines of systemic therapy; continued approval may require demonstration of benefit in confirmatory clinical trials • Kinase inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon • Tablets: 200 mg • Recommended dosage is 800 mg orally once daily with food at the same time every day until disease progression or unacceptable toxicity; prophylaxis for Pneumocystis jirovecii pneumonia (PJP) should be provided and prophylaxis for cytomegalovirus (CMV) infection, including CMV reactivation, should be considered

evinacumab-dgnb (Evkeeza™) Regeneron

• BLA approval 02/11/2021; Breakthrough Therapy, Orphan Drug, Priority Review • Indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering treatments for adults and pediatric patients ≥ 12 years with homozygous familial hypercholesterolemia (HoFH) • Safety and efficacy have not been established in patients with other causes of hypercholesterolemia (e.g., heterozygous familial hypercholesterolemia [HeFH]); effects on cardiovascular morbidity and mortality have not been established • Angiopoietin-like 3 (ANGPTL3) inhibitor • Solution for injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) in single-dose vial (SDV) • Recommended dosage is 15 mg/kg IV infusion over 60 minutes once monthly (every 4 weeks); LDL-C should be evaluated as clinically appropriate; the LDL reducing effect can be assessed as early as 2 weeks following initiation

trilaciclib dihydrochloride (Cosela™) G1 Therapeutics

• NDA approval 02/12/2021; Breakthrough Therapy, Priority Review • Indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer • Transient cyclin-dependent kinase (CDK) 4 and 6 inhibitor • Injectable: 300 mg as a lyophilized cake in a SDV • Recommended dosage is 240 mg/m2 as an IV infusion over 30 minutes completed within 4 hours before the start of chemotherapy on each day chemotherapy is administered; if discontinued, wait 96 hours from the last dose prior to resumption of chemotherapy

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.


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