MRx Clinical Alert - September 2021

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



The US FDA has approved Genzyme’s enzyme replacement therapy for late-onset Pompe disease (LOPD), avalglucosidase alfa-ngpt (Nexviazyme). Avalglucosidase alfa-ngpt is a hydrolytic lysosomal glycogen-specific enzyme indicated for treating patients ≥ 1 year old with Pompe disease, also known as glycogen storage disease type II, acid maltase deficiency, or glycogenosis type II. Dosing is based on the patient’s actual body weight (< 30 kg: 40 mg/kg or ≥ 30 kg: 20 mg/kg) and is administered IV every 2 weeks. Nexviazyme carries boxed warnings for infusion-associated reactions (IARs), hypersensitivity reactions, including anaphylaxis, and acute cardiorespiratory failure in susceptible patients.

The FDA has approved a modification to the clozapine REMS program. Beginning November 15, 2021, new requirements will be instituted: pharmacies will not be able to use the telecommunication switch system for verification of safe use conditions, a new Patient Status Form will be used for monthly monitoring of outpatients, prescribers/pharmacies will be required to be recertified by November 15, 2021, and prescribers will be required to re-enroll patients.

Pompe disease is a rare, inherited disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) that leads to accumulation of glycogen in tissues, such as the muscles. This accumulation can result in weakness as well as premature death from respiratory or cardiac failure. About 3,500 people in the US are estimated to have Pompe disease, which can be classified as either infantile-onset Pompe disease (IOPD) or LOPD, which presents at any age. Conditions that affect fewer than 200,000 people in the US are considered Orphan. Nexviazyme provides an exogenous source of GAA and includes alpha-glucosidase conjugated to bis-mannose-6-phosphate (M6P). The M6P receptor is found on the cell surface, and M6P helps to enhance uptake into lysosomes, leading to increased GAA activity that can cleave glycogen. Approval was based on a randomized, double-blinded, 49-week study (COMET) that evaluated Nexviazyme compared to Genzyme’s alglucosidase alfa (Lumizyme®) in treatment-naïve patients with LOPD. The primary endpoint of forced vital capacity (% predicted) demonstrated that Nexviazyme was non-inferior to the comparator. Superiority of Nexviazyme was not met for this endpoint; however, Nexviazyme demonstrated superiority for the secondary endpoint assessing total distance walked in 6 minutes. 2 | SEPTEMBER 2021

COVID-19 NOTABLE DEVELOPMENTS The FDA has approved the first COVID-19 vaccine, Comirnaty®, previously known as the Pfizer-Biontech COVID-19 vaccine; it is approved for prevention of COVID-19 in those ≥ 16 years old. Under EUA, the vaccine remains available for use in those 12 to 15 years old. Additionally, the FDA has amended the EUAs for this vaccine and the Moderna vaccine, both mRNA COVID-19 vaccines, to allow for an additional dose in certain immunocompromised individuals, specifically, solid organ transplant recipients or those diagnosed with conditions that are considered to have an equivalent level of immunocompromise. Furthermore, ACIP has made an interim recommendation for an additional third dose of either of these mRNA vaccines after the initial 2-dose series for those who are moderately to severely immunocompromised. The EUA for casirivimab and imdevimab (Regen-Cov™) has been revised to include use for post-exposure prophylaxis of COVID-19 in adults and pediatric individuals who are at high risk for progression to severe COVID-19, including hospitalization or death. 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 • The FDA has approved the first generic for Pfizer’s smoking cessation agent, Chantix®, as 0.5 mg and 1 mg varenicline tablets from Par. • Pfizer has voluntarily recalled an additional 4 lots of Chantix 0.5 mg/1 mg tablets to the consumer level due to the presence of N-nitroso-varenicline above the acceptable limit; this is an extension of a prior recall. • KVK Tech has voluntarily recalled 2 lots of atovaquone oral suspension, USP 750 mg/5 mL, to the consumer level due to customer complaints of unusual grittiness. This was determined to be likely due to prolonged exposure to extreme cold during shipment. • The FDA has approved pneumococcal 15-valent conjugate vaccine (Vaxneuvance™) for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in adults ≥ 18 years old. ACIP will be meeting in October to discuss and determine recommendations on the use of Vaxneuvance in adults. The immune response elicited by Vaxneuvance was non-inferior to the pneumococcal 13-valent conjugate vaccine (PCV13; Prevnar 13®) for the 13 shared serotypes and superior for shared serotype 3 and for the two serotypes unique to Vaxneuvance, 22F and 33F.

• The indication for use of nivolumab (Opdivo®) as a single agent for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib has been withdrawn. The Accelerated Approval for this use was granted in 2017. Withdrawal of this indication was based on the CheckMate-459 study that did not show overall survival benefits versus sorafenib as first-line therapy. • Romidepsin (Istodax ®) is no longer indicated for peripheral T-cell lymphoma (PTCL) in adults who have received ≥ 1 prior therapy following a withdrawal for this use. Use for PTCL was previously approved under Accelerated Approval; phase 3 confirmatory trial results demonstrated that romidepsin + CHOP (Ro-CHOP) did not meet the primary endpoint of progression free survival in first-line PTCL patients when compared with CHOP alone. • The FDA is requesting a class-wide removal of contraindications against use of statins in all pregnant patients, as the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients; therefore, contraindicating these drugs in all pregnant women is inappropriate. Most patients should stop statins once they become pregnant.

DRUG INFORMATION HAPPENINGS • The American Academy of Pediatrics (AAP) has released interim guidance on post-COVID-19 conditions. • The American College of Cardiology (ACC) has published an Expert Consensus Decision Pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia. • The CDC has published updated treatment guidelines on sexually transmitted infections. • ICER has published the final evidence report on aducanumab-avwa (Aduhelm™) for Alzheimer’s disease. • The US Preventive Services Task Force (USPSTF) has issued final recommendations on screening for gestational diabetes. Screening is recommended for gestational diabetes in asymptomatic pregnant persons at ≥ 24 weeks of gestation (Grade B).







adalimumab (biosimilar for Abbvie’s Humira®) Alvotech

• SC • TNF blocker


September 2021

atogepant Abbvie

• Oral • CGRP inhibitor

Episodic migraine prevention

September 2021

ranibizumab (biosimilar for Genentech’s Lucentis®) Biogen

• Intravitreal • VEGF inhibitor

Wet age-related macular degeneration

Sep-Oct 2021

budesonide (long-acting) Calliditas

• Oral • Corticosteroid

Immunoglobulin A (IgA) nephropathy (Berger’s disease)


ruxolitinib cream Incyte

• Topical • Janus kinase inhibitor

Atopic dermatitis (mildmoderate)


cantharidin Verrica

• Topical • Blistering agent

Molluscum contagiosum


risperidone long-acting Laboratorios Farmacéuticos Rovi

• IM • Atypical antipsychotic



maralixibat Mirum

• Oral • ASBT inhibitor

Alagille syndrome-related cholestatic pruritus


reltecimod Atox Bio

• IV • Immunomodulator

Necrotizing soft tissue infection-related organ dysfunction/failure


AS = ankylosing spondylitis; ASBT = apical sodium-dependent bile acid transporter; CD = Crohn’s disease; CGRP = calcitonin gene-related peptide; JIA = juvenile idiopathic arthritis; PsA = psoriatic arthritis; PSO = plaque psoriasis; RA = rheumatoid arthritis; TNF = tumor necrosis factor; UC = ulcerative colitis; VEGF = vascular endothelial growth factor

4 | SEPTEMBER 2021




New Drugs selexipag (Uptravi®) Janssen

• NDA approval 07/29/2021; Orphan Drug, Standard Review • Indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH • Prostacyclin receptor agonist • Injection: 1,800 mcg of lyophilized powder for reconstitution and dilution in a SDV; previously approved as oral tablets (200 mcg, 400 mcg, 600 mcg, 800 mcg, 1,000 mcg, 1,200 mcg, 1,400 mcg, and 1,600 mcg) • Recommended IV dose is based on the patient’s current oral dose of selexipag; administer IV over 80 minutes twice daily, by an HCP, in patients who are temporarily unable to take oral selexipag therapy

anifrolumab-fnia (Saphnelo™) AstraZeneca

• BLA approval 07/30/2021 • Indicated for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy • The efficacy has not been evaluated in patients with severe active lupus nephritis or severe active CNS lupus, and use is not recommended in these situations • Type I interferon receptor antagonist • Injection: 300 mg/2 mL in a SDV for further dilution • Recommended dosage is 300 mg IV over 30 minutes every 4 weeks, administered by an HCP

belzutifan (Welireg™) Merck

• NDA approval 08/13/2021; Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review, Project Orbis, Product Quality Assessment Aid, Real-Time Oncology Review (RTOR) • Indicated for treatment of adults with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), CNS hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), and who do not require immediate surgery • Hypoxia-inducible factor inhibitor • Oral tablet: 40 mg • Recommended dosage is 120 mg orally once daily with or without food, at the same time each day, taken until disease progression or unacceptable toxicity • Boxed warning regarding embryo-fetal toxicity • Product availability is expected in early September 2021

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 COVID-19 vaccine, mRNA (Comirnaty®) Pfizer-Biontech

• BLA approval 08/23/2021; Priority Review; also available under an EUA for individuals 12 to 15 years old and as a 3rd dose in certain immunocompromised individuals; the FDA has provided a Q&A on the approval • Indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals ≥ 16 years old • Nucleoside-modified mRNA vaccine • Injection: 0.45 mL suspension in a MDV for dilution to six 0.3 mL doses • Recommended dosage is a series of 2 doses (0.3 mL each) 3 weeks apart, administered IM by an HCP

difelikefalin (Korsuva™) Cara

• NDA approval 08/23/2021; Breakthrough Therapy, Priority Review • Indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis (HD) • It has not been studied in patients on peritoneal dialysis and is not recommended for use in this population • Kappa opioid receptor agonist • Injection: 65 mcg/1.3 mL (50 mcg/mL) solution in a SDV • Recommended dosage is 0.5 mcg/kg of target dry body weight administered by IV bolus into the venous line of the dialysis circuit at the end of each HD session • Product availability is expected in 1Q 2022

lonapegsomatropin-tcgd (Skytrofa™) Ascendis

• BLA approval 08/25/2021; Orphan Drug • Indicated for the treatment of pediatric patients ≥ 1 year old who weigh ≥ 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH) • Pegylated human GH (somatropin) • Injection: lyophilized powder in single-dose, dual-chamber, prefilled cartridges containing the drug and diluent in the following strengths: 3 mg, 3.6 mg, 4.3 mg, 5.2 mg, 6.3 mg, 7.6 mg, 9.1 mg, 11 mg, and 13.3 mg • Recommended dosage for treatment-naïve patients and patients switching from daily somatropin therapy is 0.24 mg/kg body weight once weekly at any time of day administered SC into the abdomen, buttock, or thigh with regular rotation of the injection sites; titrate the dose based on response; patients/caregivers can administer following proper training in injection technique

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. Glossary: ACIP Advisory Committee on Immunization Practices

CNS central nervous system COVID-19 Coronavirus Disease 2019

ASCVD atherosclerotic cardiovascular disease CDC Centers for Disease Control and Prevention CHOP cyclophosphamide, doxorubicin, vincristine, and prednisone


6 | SEPTEMBER 2021

SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

IM intramuscular

SC subcutaneous

EUA Emergency Use Authorization

IV intravenous

SDV single dose vial

FDA Food and Drug Administration

MDV multiple dose vial

US United States

mRNA messenger ribonucleic acid

USP United States Pharmacopeia

NIH National Institutes of Health

WHO World Health Organization

HCP healthcare professional

ICER Institute for Clinical and Economic Review

REMS Risk Evaluation and Mitigation Strategy © 2021, Magellan Health. All rights reserved.

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