MRx Clinical Alert - April 2021

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APRIL 2021








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




The Institute for Clinical and Economic Review (ICER) has released the Final Evidence Report on the comparative effectiveness and value of inclisiran (investigational), bempedoic acid (Nexletol®), and bempedoic acid/ ezetimibe (Nexlizet™) for the treatment of heterozygous familial hypercholesterolemia (HeFH) as well as for secondary prevention of atherosclerotic cardiovascular disease (ASCVD).

The FDA has released a summary of new efforts to support rare disease product development. A rare disease is a disease or condition that affects less than 200,000 people in the US. The agency highlights their ongoing commitment to the development of rare disease treatments even during the coronavirus disease 2019 (COVID-19) public health emergency. The agency’s 2020 accomplishments for rare diseases include the approval of 31 novel drugs (58% of novel approvals) and a novel biologic approval with Orphan Drug designation.

Oral bempedoic acid (BA), available with or without ezetimibe (EZE), is an adenosine triphosphate-citrate lyase inhibitor that reduces low-density lipoprotein cholesterol (LDL-C) by decreasing cholesterol synthesis and increasing LDL receptors. Inclisiran is a doublestranded small-interfering ribonucleic acid (siRNA) that inhibits synthesis of proprotein convertase subtilisin/ kexin type 9 (PCSK9). Inclisiran received a complete response letter (CRL) in December 2020 from the United States (US) Food and Drug Administration (FDA) due to unresolved facility inspection-related conditions. The manufacturer, Novartis, is planning to work with the FDA to complete the drug’s review. ICER concluded that evidence suggests the addition of BA to maximally tolerated oral lipid lowering drugs results in a comparable or small incremental net health benefit compared to usual care alone (“C+”). BA may result in a greater decrease in LDL-C in statin-intolerant patients. The C+ rating, also given to BA/EZE compared to EZE alone, was due to the combination’s modest effect on LDL-C levels, safety concerns, and ongoing study findings. For inclisiran, evidence suggests the addition of inclisiran to usual care of maximally tolerated oral lipid lowering therapy results in a net health benefit over usual care alone (at least small, potentially substantial). This is due to the significant decrease in LDL-C and a mechanism of action with a suggested very low likelihood for clinically important adverse effects (AEs).

2 | APRIL 2021

COVID-19 NOTABLE DEVELOPMENTS The FDA has launched the COVID-19 Emergency Use Authorization (EUA) FDA Adverse Event Reporting System (FAERS) Public Dashboard to provide weekly updates of AE data submitted to the database for drugs and biologics authorized under an EUA. The agency has updated the storage requirements for the Pfizer-BioNTech COVID-19 Vaccine, as undiluted frozen vials can be transported and stored at usual pharmaceutical freezer temperatures for up to 2 weeks. Previously, the preferred storage for these vials was in an ultra-low temperature freezer (-80°C to -60°C). The FDA has issued guidance for the development of vaccines, diagnostics, and therapeutics addressing variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. 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 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 • Bryant Ranch Prepack is voluntarily recalling 4 lots of spironolactone tablets, a diuretic, to the consumer level due to mislabeling. Prepackaged bottles labeled as spironolactone 50 mg may contain spironolactone 25 mg tablets and vice versa. Taking lower than the prescribed dose can lead to an increase in blood pressure (BP), edema, and hypokalemia associated with cardiac arrhythmias; taking higher than the prescribed dose could result in hyperkalemia, which could be life-threatening.

• The FDA has rescinded the use of coagulation factor IX, recombinant (Ixinity®) for routine prophylaxis to reduce the frequency of bleeding episodes in adolescents ≥ 12 years of age with hemophilia B. Ixinity still remains indicated for routine prophylaxis in adults, but it is no longer indicated for this use in adolescents. The adolescent routine prophylaxis indication was rescinded because recombinant coagulation factor IX (Rixubis®) carries Orphan-Drug exclusivity for this patient population.

• Genentech has announced it is voluntarily withdrawing the indication for atezolizumab (Tecentriq®) in metastatic urothelial carcinoma (bladder cancer) for patients previously treated with a platinum agent. The 2016 Accelerated Approval for this use was based on data from IMvigor210 study with continued approval for this use based on findings from IMvigor211; however, the latter study did not achieve its primary endpoint. Atezolizumab continues to be FDA-approved for certain patients with other cancers.

• Evolocumab (Repatha®) has received a new dosing regimen for patients with homozygous familial hypercholesterolemia (HoFH): 420 mg subcutaneously (SC) every 2 weeks. The initial recommended dosage for HoFH remains 420 mg once monthly; however, the dosage can be increased to 420 mg every 2 weeks if a clinical response is not reached in 12 weeks. Additionally, patients receiving lipid apheresis may initiate therapy with 420 mg every 2 weeks, corresponding with the apheresis schedule.

DRUG INFORMATION HAPPENINGS • The Kidney Disease: Improving Global Outcomes (KDIGO) released new 2021 clinical practice guidelines for BP management in patients with chronic kidney disease (CKD) not on dialysis; this is an update from the 2012 guidance. • The US Preventive Services Task Force (USPSTF) published a final recommendation statement on screening for lung cancer. The panel recommends annual screening using a low-dose computed tomography (CT) scan for people aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years (B recommendation). • The CDC has published the 2021 Advisory Committee on Immunization Practices (ACIP) recommended immunization schedule for those ≤ 18 years of age. • ICER has published a final evidence report and policy recommendations on roxadustat (investigational) and determined that the evidence is not adequate to demonstrate that roxadustat provides a net health benefit over erythropoiesis-stimulating agents (ESAs) for the treatment of CKD-related anemia. The New Drug Application (NDA) for roxadustat is currently under review by the FDA.







dapagliflozin (Farxiga®) AstraZeneca

• Oral • Sodium-glucose cotransporter 2 (SGLT2) inhibitor

Diabetic nephropathy

Apr-Jun 2021

tofacitinib (Xeljanz®/ Xeljanz XR®) Pfizer

• Oral • Janus kinase (JAK) inhibitor

Axial spondyloarthritis

Apr-Jun 2021

tralokinumab AstraZeneca

• SC • Interleukin 13 (IL-13) antagonist

Atopic dermatitis

Apr-Jun 2021

viloxazine Supernus

• Oral • Norepinephrine reuptake inhibitor

Attention deficit hyperactivity disorder (ADHD)

April 2021

pimavanserin (Nuplazid®) Acadia

• Oral • Atypical antipsychotic

Dementia-related psychosis


tramadol Fortress

• IV • Opioid analgesic

Postsurgical pain


pegunigalsidase alfa Chiesi

• IV • Agalsidase beta protein

Fabry disease


tenapanor (Isbrela®) Ardelyx

• Oral • Sodium-hydrogen exchanger (NHE) inhibitor



abrocitinib Pfizer

• Oral • JAK inhibitor

Atopic dermatitis


bupivacaine/meloxicam Heron

• Instillation • Amide anesthetic/nonsteroidal anti-inflammatory drug (NSAID)

Postsurgical pain


IV = intravenous; SC = subcutaneous

4 | APRIL 2021




New Drugs casimersen (Amondys 45) Sarepta

• NDA approval 02/25/2021; Accelerated Approval, Fast Track, Orphan Drug, Priority Review • Indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients with confirmed mutation of the DMD gene that is amenable to exon 45 skipping; continued approval may require verification of a clinical benefit in confirmatory trials • Antisense oligonucleotide (ASO) • Injection: 100 mg/2 mL in a single-dose vial (SDV) for intravenous (IV) infusion • Recommended dosage is weight-based at 30 mg/kg body weight once weekly administered by a healthcare provider (HCP) infused over 35 to 60 minutes

fosdenopterin (Nulibry™) Origin Biosciences

• NDA approval 02/26/2021; Breakthrough Therapy, Orphan Drug, Priority Review • Indicated for mortality risk reduction in patients with molybdenum cofactor deficiency (MoCD) type A as confirmed by genetic testing • Cyclic pyranopterin monophosphate (cPMP) • Injection: 9.5 mg as a lyophilized powder or cake in a SDV for reconstitution • Recommended dosage is based on patient’s age and is weight-based for those < 1 year old; administered as a 1.5 mL/minute IV infusion by an HCP or administered at home by the patient’s caregiver, if appropriate » Preterm neonates: initial dosage of 0.4 mg/kg once daily, increased up to 0.9 mg/kg once daily in month 3 » Term neonates: initial dosage of 0.55 mg/kg once daily, increased up to 0.9 mg/kg once daily in month 3 » Patients ≥ 1 year old: 0.9 mg/kg once daily

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 melphalan flufenamide (Pepaxto®) Oncopeptides

• NDA approval 02/26/2021; Accelerated Approval, Orphan Drug, Priority Review • Indicated for use, in combination with dexamethasone, in adults with relapsed or refractory 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 monoclonal antibody; continued approval may require demonstration of benefit in confirmatory clinical trials • Not indicated and not recommended for use as a conditioning regimen for transplant outside of controlled clinical trials • Alkylating drug • Injection: 20 mg as a lyophilized powder in a SDV for reconstitution • Recommended dosage is 40 mg IV over 30 minutes on day 1 of each 28-day treatment cycle administered by an HCP until disease progression or until unacceptable toxicity

serdexmethylphenidate/ dexmethylphenidate (Azstarys™) Corium

• 505(b)(2) NDA approval 03/02/2021 • Indicated for treatment of ADHD in patients ≥ 6 years • Central nervous system (CNS) stimulant • Oral capsule: 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, and 52.3 mg/10.4 mg • Recommended dosage is taken once daily in the morning, without regard to food: » Patients aged 6 to 12 years: 39.2 mg/7.8 mg starting dosage, increased to 52.3 mg/10.4 mg or decreased to 26.1 mg/5.2 mg daily after 1 week » Adults and pediatric patients aged 13 to 17 years: 39.2 mg/7.8 mg starting dosage, increase to 52.3 mg/10.4 mg daily after 1 week » Capsules can be swallowed whole, opened and sprinkled onto applesauce or added to water • Boxed warning for abuse and dependence • Drug Enforcement Administration (DEA) controlled substance scheduling pending within 90 days of FDA approval; FDA recommended Schedule II • Product availability is expected in 2H 2021

tivozanib (Fotivda®) Aveo

• NDA approval 03/10/2021 • Indicated for use in adults with relapsed or refractory advanced renal cell carcinoma (RCC) following ≥ 2 prior systemic therapies • Tyrosine kinase inhibitor, including vascular endothelial growth factor (VEGF) receptor, c-kit, and platelet-derived growth factor (PDGF) receptor β • Oral capsule: 1.34 mg and 0.89 mg • Recommended dosage is 1.34 mg once daily without regard to food for 21 days, followed by 7 days off therapy; dosage reduction to 0.89 mg in hepatic impairment; repeat 28-day cycle until disease progression or unacceptable toxicity

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 | APRIL 2021



New Drugs continued oritavancin (Kimyrsa™) Melinta

• NDA approval 03/12/2021 • Indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms; to decrease the development of drug-resistant bacteria and maintain the effectiveness of this agent and other antibacterial drugs, it should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria • Lipoglycopeptide antibacterial drug • Injection: 1,200 mg of lyophilized powder in a SDV for reconstitution; there is another oritavancin product (Orbactiv®) that differs in dose strength, infusion duration, and preparation instructions (e.g., reconstitution and dilution instructions; compatible diluents) • Recommended dosage is 1,200 mg as a single dose by IV infusion over 1 hour • Product availability is expected in summer 2021

ponesimod (Ponvory™) Janssen

• NDA approval 03/18/2021 • Indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults • Sphingosine 1-phosphate receptor modulator • Oral tablets: 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, and 20 mg • Recommended maintenance dosage is 20 mg once daily starting on day 15, following initial titration; 1st-dose monitoring is recommended for certain patients

dasiglucagon (Zegalogue®) Zealand

• NDA approval 03/22/2021 • Indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes aged ≥ 6 years • Antihypoglycemic agent • Injection: 0.6 mg/0.6 mL single-dose autoinjector and single-dose prefilled syringe • Recommended dosage is 0.6 mg SC into the lower abdomen, buttocks, thigh, or outer upper arm, then call for emergency assistance immediately after administering; if no response after 15 minutes, an additional dose may be given while waiting for emergency assistance; oral carbohydrates should be given once the patient responds to therapy • Product availability is expected in June 2021


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