Clinical Alert October 2022

TRENDING TOPICS

NEW PLAQUE PSORIASIS DRUG: SOTYKTU™

The US FDA has approved a novel oral agent for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Deucravacitinib (Sotyktu) is a firstin-class tyrosine kinase 2 (TYK2) inhibitor. TYK2 is a member of the JAK family, and deucravacitinib carries a warning stating it is unknown whether TYK2 inhibition is associated with adverse events of JAK inhibition, such as increased all-cause mortality, MACE, thromboembolic events, and malignancies. Deucravacitinib is not recommended for use in combination with other potent immunosuppressants and carries warnings regarding the potential for infections, tuberculosis (TB), malignancy, hypersensitivity, rhabdomyolysis, as well as elevated creatine phosphokinase (CPK), triglycerides, and liver enzymes.

Deucravacitinib is a 6 mg oral tablet taken once daily. Patients should be assessed for active and latent TB and all age-appropriate vaccinations should be considered before starting therapy. The efficacy and safety were evaluated in 2 multicenter, randomized, doubleblind, placebo- and active-controlled clinical trials, PSO-1 and PSO-2. The coprimary efficacy endpoints evaluating the proportion of subjects at week 16 with clear or almost clear skin (sPGA score of 0 or 1) and ≥ 75% improvement from baseline in psoriasis severity (PASI 75) were significantly improved with deucravacitinib, compared to placebo in both PSO1 (sPGA: difference, 47%; 95% CI, 40 to 53; PASI 75: difference, 46%; 95% CI, 39 to 53) and PSO-2 (sPGA: difference, 41%; 95% CI, 35 to 46; PASI 75: difference, 44%; 95% CI, 38 to 49). Deucravacitinib treatment also resulted in significant improvements in secondary endpoints compared to active comparator apremilast (Otzela®) in both PSO-1 (sPGA: difference, 22%; 95% CI, 13 to 30; PASI 75: difference, 23%; 95% CI, 14 to 32) and PSO-2 (sPGA: difference, 16%; 95% CI, 9 to 23; PASI 75: difference, 13%; 95% CI, 6 to 21). Across the studies, a higher proportion of deucravacitinib-treated patients reported a symptom score of 0 (PSSD) at week 16 compared to placebo patients (8% versus 1%).

BIOSIMILAR CORNER: STIMUFEND®

A new biosimilar to pegfilgrastim (Neulasta®) has received FDA approval. Pegfilgrastim-fpgk (Stimufend) is a leukocyte growth factor indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Neulasta is also indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation; Stimufend does not carry this indication. Both Neulasta and Stimufend carry a limitation of use stating the products are not indicated for mobilization of peripheral blood progenitor cells for hematopoietic stem cell (HSC) transplantation. Neulasta is supplied as a solution in a single-dose prefilled syringe (6 mg/0.6 mL) for manual use as well as co-packaged with the on-body Neulasta injector. Stimufend is expected to be commercially available in a 6 mg/0.6 mL single-dose prefilled syringe for manual use in early 2023. Stimufend is the sixth biosimilar to Neulasta.

COVID-19: NOTABLE DEVELOPMENTS

The CDC has endorsed ACIP’s recommendations re garding use of the updated bivalent Omicron BA.4/5 COVID-19 boosters from Pfizer-Biontech and Moderna for use in those ≥ 12 years old and adults, respectively. Pfizer-Biontech has released updated efficacy data on use of their COVID-19 vaccine in children 6 months to 4 years old. The CDC has published an MMWR detailing COVID-19 mRNA vaccine safety in children 6 months to 5 years old. Additionally, an MMWR has been pub lished on safety data from booster doses of the PfizerBiontech COVID-19 vaccine in children 5 years to 11 years old. The CDC has released an MMWR on laboratory-confirmed COVID-19-associated hospital izations in adults during the period of Omicron BA.2 predominance that demonstrated hospitalization rates were about 3 times greater among unvaccinated indi viduals than those who were vaccinated. Please refer to the COVID-19 disclaimer at the end of the publication.

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

• The FDA is warning that autoinjector devices that are optional for use with glatiramer acetate injection may not be compatible for use across FDA-approved glatiramer acetate injection products (Copaxone ® , Glatopa ® , generic). These products are available in single-dose prefilled syringes with a needle for SC use. Patients may administer using only the syringe or by inserting the syringe into an autoinjector. The autoinjectors are reusable and are available by prescription separately. Using a noncompatible autoinjector has led to missed and partial doses.

• Lumacaftor/ivacaftor (Orkambi®) has received an expanded indication for the treatment of cystic fibrosis in patients ≥ 1 year old who are homozygous for the F508del mutation in the CFTR gene; previously, it was indicated for patients ≥ 2 years old. In pediatric patients < 6 years old, dosing of oral granules is weight-based. A new strength of oral granules, lumacaftor 75 mg and ivacaftor 94 mg, was also approved.

• Niraparib’s (Zejula™) labeling has been updated with the removal of the indication for adults with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥ 3 prior chemotherapy regimens and whose cancer is associated with HRD positive status. Niraparib’s other indications for the maintenance treatment of certain adult ovarian cancer patients remain.

• AstraZeneca has voluntarily withdrawn olaparib’s (Lynparza®) indication for adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with ≥ 3 prior lines of chemotherapy. Olaparib maintains indications for select patients with ovarian, breast, pancreatic, and prostate cancer.

• With a record number of drug overdose deaths in 2021, the FDA has introduced the Overdose Prevention Framework with 4 priorities: 1) primary prevention, 2) harm reduction, 3) treatments for SUD, and 4) protection from unapproved/diverted drugs.

DRUG INFORMATION HAPPENINGS

• The American College of Cardiology (ACC) has published an Expert Consensus Decision Pathway on the use of non-statin therapies for lowering LDL-cholesterol in managing ASCVD risk.

• The CDC has published updated recommendations from the ACIP on the use of the 15-valent pneumococcal conjugate vaccine among children in the US.

• The CDC has published ACIP’s recommendations for prevention and control of seasonal influenza with vaccines and has updated the Frequently Asked Influenza Questions for the upcoming influenza season. The American Academy of Pediatrics (AAP) has also released influenza recommendations for management in children.

• The US Preventive Services Task Force (USPSTF) has issued a Final Recommendation Statement on statin use for the primary prevention of CVD in adults. For adults aged 40 to 75 years with ≥ 1 CV risk factor (e.g., dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD risk of ≥ 10%, a statin is recommended for the primary prevention of CVD (Grade B). For adults aged 40 to 75 years with ≥ 1 CV risk factors and an estimated 10-year CVD risk of 7.5% to < 10%, a statin can be selectively offered for the primary prevention of CVD as the potential for a benefit is smaller in this group than in persons with a 10-year risk of ≥ 10% (Grade C). For adults ≥ 76 years, the current evidence is inadequate to determine the benefits versus risks of starting statin therapy for the primary prevention of CVD events and mortality (Grade I).

PIPELINE

UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES

DRUG NAME MANUFACTURER

aflibercept (biosimilar to Regeneron’s Eylea®) Viatris/Janssen

THERAPEUTIC CLASS

Intravitreal

Vascular endothelial growth factor (VEGF) inhibitor

PROPOSED CLINICAL USE

Diabetic macular edema; Diabetic retinopathy; Macular edema following retinal vein occlusion; Neovascular (wet) age-related macular degeneration

adalimumab 50 mg/mL (biosimilar to Abbvie’s Humira®)

Fresenius

tremelimumab

AstraZeneca

SC

Tumor necrosis factor-alpha (TNF-α) inhibitor

IV

Cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) inhibitor

Rheumatoid arthritis; Ankylos ing spondylitis; Plaque psoria sis; Psoriatic arthritis; Juvenile idiopathic arthritis; Crohn’s disease; Ulcerative colitis

Hepatocellular carcinoma (single priming dose for durvalumab)

APPROVAL

October 2022

Fecal microbiota, liv3 Ferring

apomorphine infusion pump Supernus

furosemide

cipaglucosidase alfa Amicus

Rectal

Microbiome therapy

SC

Dopamine receptor

Clostridioides difficile infection (recurrent)

Oct to Dec 2022

Oct to Dec 2022

Oct to Dec 2022

Parkinson’s disease 10/07/2022

SC

IV

Enzyme replace ment therapy

Decompensated heart failure 10/08/2022

Pompe disease (in combination with oral miglustat)

ibrutinib (Imbruvica®)

Pharmacyclics

RECENT FDA APPROVALS

DESCRIPTION

New Drugs

• NDA approval 08/24/2022; Orphan Drug, Priority Review

• Indicated for pediatric patients ≥ 1 year of age with chronic graft-versushost disease (cGVHD) after failure of ≥ 1 lines of systemic therapy; ibrutinib is also indicated for use in adults with cGVHD after failure of ≥ 1 lines of systemic therapy and in certain adults with mantle cell lymphoma, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström's macroglobulinemia, and marginal zone lymphoma

• Kinase inhibitor

• Oral suspension: 70 mg/mL; also available as capsules and tablets

• Recommended dosage for cGVHD in patients 1 to < 12 years of age is 240 mg/m2 taken once daily (up to a dose of 420 mg); for patients ≥ 12 years old, the recommended dosage is 420 mg orally once daily for cGVHD

omeprazole/sodium bicarbonate (Konvomep™) Azurity

• 505(b)(2) NDA approval 08/30/2022; Standard Review

• Indicated in adults for the short-term treatment of active benign gastric ulcer and for the reduction of risk of upper gastrointestinal (GI) bleeding in critically ill patients

• Combination of a proton pump inhibitor (PPI) and sodium bicarbonate

• Oral suspension: 2 mg omeprazole and 84 mg sodium bicarbonate per mL after reconstitution; packaged as a kit containing 1 bottle of omeprazole and 1 bottle of strawberry-flavored diluent containing sodium bicarbonate; omeprazole/sodium bicarbonate is also currently available in capsules and powder/granules for suspension

• Recommended dosage for the short-term treatment of active benign gastric ulcer is 40 mg once daily for 4 to 8 weeks; for the reduction of risk of upper GI bleeding in critically ill patients, the recommended dosage is 40 mg once daily with a loading dose of two 40 mg doses given 6 to 8 hours apart on the first day for 14 days; suspension may be administered in a nasogastric or orogastric feeding tube

• Product availability is expected in 1Q 2023

RECENT FDA APPROVALS continued

olipudase alfa-rpcp (Xenpozyme™) Genzyme

spesolimab-sbzo (Spevigo®)

Boehringer Ingelheim

eflapegrastim-xnst (Rolvedon™) Spectrum

terlipressin (Terlivaz®) Mallinckrodt

New Drugs continued

• BLA approval 08/31/2022; Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review, Rare Pediatric Disease Designation

• Indicated for the treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients

• Hydrolytic lysosomal sphingomyelin-specific enzyme

• Injection: 20 mg as a lyophilized powder in an SDV for reconstitution

• Recommended starting dosage in adults is 0.1 mg/kg IV infusion and in pediatric patients is 0.03 mg/kg IV infusion with a dose escalation regimen every 2 weeks, to a maintenance dose of 3 mg/kg every 2 weeks for both adults and pediatric patients; for patients with a body mass index (BMI) ≤ 30, the dose is based on actual body weight; for patients with a BMI > 30, the dose is based on adjusted body weight

• Boxed warning regarding the risk for severe hypersensitivity reactions

• BLA approval 09/01/2022; Breakthrough Therapy, Orphan Drug, Priority Review

• Indicated for the treatment of generalized pustular psoriasis flares in adults

• Interleukin-36 receptor antagonist

• Injection: 450 mg/7.5 mL (60 mg/mL) solution in an SDV

• Recommended dosage is a single 900 mg IV infusion administered by an HCP over 90 minutes; administration may be repeated in 1 week if flare symptoms persist

• BLA approval 09/09/2022

• Indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia

• Not indicated for the mobilization of peripheral blood progenitor cells for HSC transplantation

• Leukocyte growth factor

• Injection: 13.2 mg/0.6 mL solution in a single-dose prefilled syringe

• Recommended dosage is 13.2 mg SC once per chemotherapy cycle by an HCP; administer approximately 24 hours after cytotoxic chemotherapy

• Product availability is expected in 4Q 2022

• NDA approval 09/14/2022; Orphan Drug, Priority Review

• Indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function

• Patients with a serum creatinine > 5 mg/dL are unlikely to derive benefit

• Vasopressin receptor agonist

• Injection: 0.85 mg as a lyophilized powder in an SDV for reconstitution

• Recommended starting dosage is 0.85 mg IV over 2 minutes administered by an HCP every 6 hours on days 1 to 3; dosage for days 4 to 14 is dependent on response compared to baseline serum creatinine

• Boxed warning regarding serious or fatal respiratory failure

• Product availability expected in the coming weeks

RECENT FDA APPROVALS continued

elivaldogene autotemcel (eli-cel) (Skysona®) Bluebird Bio

omidenepag isopropyl (Omlonti®) Santen

New Drugs continued

• BLA approval 09/16/2022; Accelerated Approval, Breakthrough Therapy, Orphan Drug, Priority Review, Rare Pediatric Disease Designation

• Indicated to slow the progression of neurologic dysfunction in boys 4 to 17 years of age with early, active cerebral adrenoleukodystrophy (CALD); early, active CALD refers to asymptomatic or mildly symptomatic (neurologic function score ≤ 1) boys who have gadolinium enhancement on brain MRI and Loes scores of 0.5 to 9

• Accelerated Approval is based on 24-month major functional disability-free survival, and continued approval may require demonstration of benefit in confirmatory clinical trials

• Limitations of use: 1) does not treat or prevent adrenal insufficiency; 2) an immune response to the drug may cause rapid loss of efficacy for the agent in patients with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 (ABCD1) gene; 3) has not been studied in CALD secondary to head trauma; and 4) given the risk of hematologic malignancy and unclear long-term durability of the agent and human adrenoleukodystrophy protein expression, careful consideration should be given to when treatment begins and treatment of boys with isolated pyramidal tract disease, as clinical manifestations do not usually occur until adulthood

• Autologous HSC-based gene therapy

• Cell suspension: 4 to 30 × 106 cells/mL in 1 or 2 infusion bags; patients undergo HSC mobilization followed by apheresis to obtain CD34+ cells for manufacturing

• Minimum recommended dosage is 5 × 106 CD34+ cells/kg (autologous use only) given as a one-time, single-dose IV infusion over < 60 minutes with full myeloablative and lymphodepleting conditioning prior to the infusion

• Boxed warning for hematologic malignancy

• Product will be available only at Qualified Treatment Centers by the end of 2022

• NDA approval 09/22/2022; Standard Review

• Indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension

• Relatively selective prostaglandin E2 receptor agonist

• Ophthalmic solution: 0.002% (0.02 mg/mL)

• Recommended dosage is 1 drop in the affected eye(s) once daily in the evening

505(b)(2)

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.

Glossary:

ACIP Advisory Committee on Immunization Practices

ASCVD atherosclerotic cardiovascular disease

BLA Biologics License Application

BRCA BReast CAncer gene

CDC Centers for Disease Control and Prevention

CFTR cystic fibrosis transmembrane conductance regulator

CI confidence interval

COVID-19 Coronavirus Disease 2019

CV cardiovascular

CVD cardiovascular disease

FDA Food and Drug Administration

HCP healthcare professional

HRD homologous recombination deficiency

IV intravenous

JAK Janus kinase

LDL low-density lipoprotein

MACE major adverse cardiovascular events

MMWR Morbidity and Mortality Weekly Report

MRI magnetic resonance imaging

mRNA messenger ribonucleic acid

NDA New Drug Application

NIH National Institutes of Health

PASI Psoriasis Area and Severity Index

PSSD Psoriasis Symptoms and Signs Diary

Q quarter

RPh registered pharmacist

SC subcutaneous

SDV single-dose vial

sPGA static Physician’s Global Assessment

SUD substance use disorder

US United States

WHO World Health Organization

References:

aap.org cdc.gov fda.gov jacc.org uspstf.org