Clinical Alert October 2023

OCTOBER 2023

C LINICAL

ALERT

Your Monthly Source for Drug Information Highlights

EDITORIAL STAFF

EDITOR-IN-CHIEF

Maryam Tabatabai

PharmD

EXECUTIVE EDITOR

Anna Schreck Bird

PharmD

DEPUTY EDITORS

Jessica Czechowski

PharmD

Carole Kerzic

RPh

Olivia Pane

PharmD, CDCES

TRENDING TOPICS

WEIGHT MANAGEMENT CORNER

COVID-19 NOTABLES

BIOSIMILAR UPDATES

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

TRENDING TOPICS

HOT TOPIC – ABRYSVO™ NEW INDICATION

The respiratory syncytial virus (RSV) vaccine Abrysvo has received approval for use in pregnant individuals for the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by RSV in infants from birth through 6 months of age. It is the first vaccine to receive approval for this indication and is given as a single 0.5 mL IM dose from 32 to 36 weeks gestational age of pregnancy. RSV is the most common cause of LRTD in infants globally, and in the US it is the most common reason for infant hospitalization. Abrysvo is also indicated for prevention of LRTD caused by RSV in adults ≥ 60 years of age. Approval for the new use was based on a randomized, double-blinded, phase 3 global study (n=7,332). The vaccine was studied in pregnant individuals between 24 to 36 weeks gestational age (GA). Vaccine efficacy (VE) as a reduction in medically attended LRTD and severe LRTD caused by RSV in infants from birth to 6 months when administered at 32 to 36 weeks GA (subgroup), showed that compared to placebo, VE against severe LRTD caused by RSV was found to be 91.1% (95% CI, 38.8 to 99.8) at 90 days and 76.5% (95% CI, 41.3 to 92.1) at 180 days. A statistically significant difference in VE against LRTD caused by RSV was not reached at 90 days (VE: 34.7%; 95% CI, -34.6 to 69.3) but was achieved at 180 days (VE: 57.3%; 95% CI, 29.8 to 74.7). The most common ADRs experienced with Abrysvo compared to placebo, respectively, were pain at the injection site (40.6% versus 10.1%), headache (31% versus 27.6%), muscle pain (26.5% versus 17.1%), and nausea (20% versus 19.2%). Abrysvo carries a warning on the potential for preterm births. The CDC recommends maternal RSV vaccination in pregnant persons from 32 to 36 weeks gestation to prevent RSV infection in infants.

FDA COMMITTEE REVIEWS PHENYLEPHRINE

The FDA’s Non-prescription Drug Advisory Committee (Ad Com) reviewed new data on oral phenylephrine and determined that it is not effective as a nasal decongestant at the recommended dosages. Although there are no concerns regarding the product’s safety, the FDA will be assessing the data and considering the Ad Com’s recommendations as it reviews the drug’s efficacy.

WEIGHT MANAGEMENT CORNER

The CDC has published data from 2022 demonstrating 22 states have adult obesity prevalence ≥ 35%. In contrast, no states had an adult obesity prevalence of this level 10 years ago. Population-based interventions are needed for obesity prevention and treatment.

Due to increased demand, certain strengths (0.25 mg/0.5 mL, 0.5 mg/0.5 mL, 1 mg/0.5 mL) of Novo Nordisk’s semaglutide (Wegovy®) have limited availability. Novo Nordisk plans to continue restrictions on starter doses of Wegovy into 2024. Additionally, availability is limited through the end of 2023 for the 2.68 mg/1 mL semaglutide (Ozempic®) injection.

COVID-19: NOTABLE DEVELOPMENTS

The FDA has approved and authorized for emergency use updated Moderna and Pfizer-Biontech COVID-19 vaccines for the Omicron variant XBB.1.5. These updated monovalent vaccines replace the bivalent (original and Omicron BA.4/BA.5) vaccines and are expected to be available this fall. The mRNA vaccines are approved for individuals ≥ 12 years of age and are authorized under emergency use for individuals 6 months through 11 years of age. The CDC’s recommendations are for everyone ≥ 6 months of age to receive an updated COVID-19 vaccine. Please refer to the COVID-19 disclaimer at the end of this publication.

BIOSIMILAR CORNER: UPDATES

Natalizumab-sztn (Tyruko ® ), the first biosimilar to natalizumab (Tysabri®), has received FDA approval. Tyruko is approved as monotherapy for adults to treat relapsing forms of multiple sclerosis (MS). It is also indicated for certain adults with moderately- to severely-active Crohn’s disease (CD). Due to the risk of progressive multifocal leukoencephalopathy (PML), natalizumab products only are available through a REMS program.

Adalimumab-atto (Amjevita™), a biosimilar to adalimumab (Humira®), has received approval for additional strengths of SureClick® autoinjectors (40 mg/0.4 mL and 80 mg/0.8 mL) and additional strengths of prefilled glass syringes (20 mg/0.2 mL, 40 mg/0.4 mL, and 80 mg/0.8 mL).

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

• Marlex has voluntarily recalled 1 lot of digoxin tablets, USP 0.125 mg and 1 lot of digoxin tablets, USP 0.25 mg to the consumer level due to a label mix-up that can result in either overdosing or underdosing. Although the manufacturer has not received reports of ADRs related to the recall, overdosing could result in drug toxicity (e.g., disorientation, dizziness, blurred vision, memory loss, fainting) and underdosing could lead to a heart failure exacerbation.

• Novartis has issued a voluntary recall for 1 lot of cyclosporine oral solution, USP (Sandimmune ® ) 100 mg/mL due to crystallization that could lead to incorrect dosing. The impacted lot was distributed nationwide starting in April 2023. The recall is to the consumer, HCP, and distributor level.

• The FDA has published a communication instructing patients to immediately stop use of certain methylsulfonylmethane (MSM) eye drops due to bacterial and/or fungal contamination. These products are Dr Berne’s MSM Drops 5% Solution and LightEyez MSM Eye Drops – Eye Repair. Although the FDA has not reported any ADRs associated with these products, contaminated eye drops could lead to serious visionthreatening infection with possible progression to life-threatening infection.

• Horizon has made a business decision to discontinue manufacture of ibuprofen/famotidine (Duexis®). It is indicated to decrease the risk for upper GI ulcers in patients receiving ibuprofen for RA or OA.

• The therapeutic equivalence rating for Accord’s tacrolimus oral capsule (generic for Prograf®) has been changed from AB to BX. As a result, Accord’s tacrolimus oral capsule cannot be automatically substituted for Prograf oral capsules at the pharmacy. This change was based on data demonstrating that maximum blood levels may be greater with the Accord generic than with brandname Prograf, thereby potentially increasing the risk for toxicity. No significant differences in trough blood concentrations (no increased risk for organ rejection) were observed. Other tacrolimus formulations, as well as other manufacturers’ generic oral capsules, are not affected. An HCP should be consulted prior to a patient changing their tacrolimus therapy.

• Moderna’s mRNA COVID-19 vaccine (Spikevax®) has received an expanded indication to include use in individuals 12 to 17 years old as a single dose of the updated 2023 to 2024 formulation for recipients ≥ 12 years of age.

• The SARS-CoV-2 nucleotide analog RNA polymerase inhibitor remdesivir (Veklury®) has received a label update as patients with mild, moderate, or severe hepatic impairment do not require a dose adjustment. Previously, labeling stated that the pharmacokinetics had not been assessed in these patients. It is indicated for treatment of COVID-19 in adults and certain pediatric patients who are hospitalized or who have mild-tomoderate COVID-19 and are at high-risk for progression to severe COVID-19, including hospitalization or death.

DRUG INFORMATION HAPPENINGS

• The OTC opioid reversal nasal spray, naloxone (Narcan®), is now available nationwide.

• The AAP has updated pediatric influenza vaccine recommendations for the 2023 to 2024 season.

• The ACIP has published an MMWR on recommendations for pneumococcal vaccination for adults ≥ 19 years old.

• ICER issued a final evidence report on use of gene therapies for sickle cell disease.

• The USPSTF issued a final recommendation on the use of preexposure prophylaxis with effective antiretroviral therapy to decrease the potential for acquiring HIV in individuals who are at increased risk (Grade A).

• The FDA updated guidance for treating molluscum contagiosum following the approval of cantharidin (Ycanth™).

PIPELINE NEWS

UPCOMING PRESCRIPTION

binimetinib (Mektovi®) + encorafenib (Braftovi®)

• Oral/oral

• Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor/B-Raf proto-oncogene (BRAF) kinase inhibitor

cell lung cancer (BRAF V600E mutation, metastatic)

(HR+/HER2-, R/R, locally advanced or metastatic, combined with fulvestrant)

(Dupixent®) Sanofi

pilocarpine 0.4% Orasis

adapalene/benzoyl peroxide/clindamycin

Bausch Health

clobetasol propionate Salvat

vamorolone Santhera

• SC

• Interleukin-4 receptor (IL-4R) antagonist

• Ophthalmic

• Muscarinic receptor agonist

Urticaria (chronic, spontaneous, ages ≥ 12 years)

• Retinoid/bactericide/ lincosamide antibiotic Acne vulgaris

• Topical

• Ophthalmic (nanoemulsion)

• Corticosteroid

• Oral

• Dissociative steroid

Postsurgical ocular pain and inflammation

muscular dystrophy

RECENT FDA APPROVALS

DRUG NAME MANUFACTURER

aflibercept (Eylea® HD)

Regeneron

melphalan (no trade name)

Apotex

pozelimab-bbfg (Veopoz™)

Regeneron

DESCRIPTION

New Drugs

• BLA approval 08/18/2023; Standard Review

• Indicated for treatment of neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy (DR)

• Vascular endothelial growth factor (VEGF) inhibitor

• Injection: 8 mg (0.07 mL of 114.3 mg/mL solution) in an SDV

• Recommended dosage for all indications is 8 mg administered via intravitreal injection by a qualified HCP every 4 weeks for the first 3 doses, then 8 mg via intravitreal injection by a qualified HCP once every 8 to 12 weeks for DR or once every 8 to 16 weeks for AMD or DME

• 505(b)(2) NDA approval 08/18/2023; Standard Review

• Indicated for the palliative treatment of patients with multiple myeloma for whom oral treatment is not appropriate

• Alkylating drug

• Injection: 90 mg/mL injection in an MDV

• Recommended dosage is 16 mg/m² IV administered over 15 to 20 minutes at 2-week intervals for 4 doses, then at 4-week intervals after adequate recovery from toxicity

• Boxed warning for severe bone marrow suppression, hypersensitivity, and leukemogenicity

• BLA approval 08/18/2023; Fast Track, Orphan Drug, Priority Review, Rare Pediatric Disease

• Indicated for adult and pediatric patients ≥ 1 year of age with CD55-deficient proteinlosing enteropathy (PLE; also known as complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy [CHAPLE] disease)

• Complement inhibitor

• Injection: 400 mg/2 mL in an SDV

• Recommended dosage is a single 30 mg/kg IV loading dose on day 1, then 10 mg/kg SC once weekly starting on day 8 and thereafter (maintenance dose); all doses must be administered by an HCP; the maintenance dose may be increased to 12 mg/kg SC once weekly if there is inadequate clinical response after at least 3 weekly doses; maximum weekly dose is 800 mg

• Boxed warning for serious meningococcal infections

RECENT FDA APPROVALS continued

DRUG NAME MANUFACTURER DESCRIPTION

fosaprepitant (Focinvez) Spes

• 505(b)(2) NDA approval 08/22/2023; Standard Review

• Indicated for use in adults and pediatric patients ≥ 6 months of age, in combination with other antiemetic agents, for prevention of:

» Acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC), including high-dose cisplatin;

» Delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)

• This product has not been studied for treatment of established nausea and vomiting

• Substance P/neurokinin-1 (NK1) receptor antagonist

• Injection: 150 mg/50 mL (3 mg/mL) in an SDV

• Recommended dosage for adults is 150 mg on day 1 as an IV infusion over 20 to 30 minutes, completed approximately 30 minutes before chemotherapy

• Recommended dosage for pediatric patients varies based on age and if the patient is on single-day or multiple-day chemotherapy regimens; details are provided in the prescribing information

crizotinib (Xalkori®) Pfizer

• NDA approval 09/07/2023; Orphan Drug, Standard Review

• Indicated for:

» Adults with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)- or ROS1-positive, as detected by an FDA-approved test;

» Pediatric patients ≥ 1 year of age and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive;

» Adult and pediatric patients ≥ 1 year of age with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive

• Kinase inhibitor

• Oral pellets: 20 mg, 50 mg, 150 mg; already approved as oral capsule (200 mg, 250 mg)

• Recommended adult dosage for metastatic NSCLC and unresectable IMT is 250 mg orally twice daily and 280 mg/m2 orally twice daily for systemic ALCL

• Recommended pediatric dose is 280 mg/m2 orally twice daily for unresectable IMT and systemic ALCL

• Pellets are supplied encapsulated in shells; the pellets encapsulated in the shell should not be swallowed; the shell should be opened and the pellets either administered directly into patient’s mouth or into a spoon/medicine cup; following administration, an adequate amount of water should be consumed for all the pellets to be swallowed; do not chew or crush the pellets

motixafortide (Aphexda™)

BioLineRx

• NDA approval 09/08/2023; Orphan Drug, Standard Review

• Indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma

• Hematopoietic stem cell mobilizer

• Injection: 62 mg lyophilized powder in an SDV for reconstitution

• Recommended dosage is 1.25 mg/kg actual body weight SC 10 to 14 hours prior to initiation of apheresis; a 2nd dose can be administered 10 to 14 hours prior to a 3rd apheresis; initiate motixafortide after filgrastim has been given daily for 4 days

RECENT FDA APPROVALS continued

DRUG NAME MANUFACTURER

momelotinib (Ojjaara™)

GlaxoSmithKline

gepirone (Exxua™)

Fabre-Kramer

metronidazole (Likmez™) Saptalis

phentolamine ophthalmic solution (Ryzumvi™)

Ocuphire

DESCRIPTION

• NDA approval 09/15/2023; Orphan Drug, Standard Review

• Indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF (post-polycythemia vera [PV] and post-essential thrombocythemia [ET]) in adults with anemia

• Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 inhibitor

• Oral tablet: 100 mg, 150 mg, 200 mg

• Recommended dosage is 200 mg orally once daily with or without food; the starting dose is reduced to 150 mg orally once daily in patients with severe hepatic impairment (Child-Pugh Class C); dosage modifications for ADRs are detailed in the prescribing information

• NDA approval 09/22/2023; Standard Review

• Indicated for the treatment of major depressive disorder in adults

• Antidepressant

• Extended-release tablet: 18.2 mg, 36.3 mg, 54.5 mg, 72.6 mg

• Recommended starting dosage of 18.2 mg orally once daily with food at approximately the same time each day; based on response and tolerability, the dosage may be increased to 36.3 mg once daily on day 4 and may be further titrated to 54.5 mg once daily after day 7 and to 72.6 mg once daily after an additional week

• Electrolyte abnormalities should be corrected and ECGs performed before starting treatment; ECGs should also be performed during dose titration and regularly during treatment

• Boxed warning for suicidal thoughts and behaviors

• Product availability is expected in early 2024

• 505(b)(2) NDA approval 09/22/2023; Standard Review

• Indicated for the treatment of trichomoniasis in adults, amebiasis in adults and pediatric patients, and anaerobic bacterial infections in adults

• Nitroimidazole antimicrobial

• Oral suspension: 500 mg/5 mL

• Recommended dosage is dependent on the indication, patient age and/or body weight

• Boxed warning regarding potential for carcinogenicity

• 505(b)(2) NDA approval 09/25/2023; Standard Review

• Indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agent

• Alpha adrenergic blocker

• Ophthalmic solution: 0.75% in single-patient-use vials

• Recommended dosage for patients ≥ 12 years old is to instill 1 to 2 drops in each dilated eye following the completion of the ophthalmic examination or procedure to reverse mydriasis; for pediatric patients 3 to 11 years old, instill 1 drop in each dilated eye following the completion of the ophthalmic examination or procedure to reverse mydriasis

RECENT FDA APPROVALS continued

DRUG NAME MANUFACTURER

cipaglucosidase alfa-atga (Pombiliti™)

Amicus

miglustat (Opfolda™)

Amicus

DESCRIPTION

• BLA approval 09/28/2023; Breakthrough Therapy, Orphan Drug

• Indicated in combination with Opfolda for the treatment of adults with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥ 40 kg and who are not improving on their current enzyme replacement therapy (ERT)

• Hydrolytic lysosomal glycogen-specific enzyme

• Injection: 105 mg of lyophilized powder in an SDV for reconstitution

• Recommended dosage is 20 mg/kg (actual body weight) administered every other week as an IV infusion over approximately 4 hours; the infusion should be started about 1 hour after oral administration of Opfolda; initiate in combination with Opfolda 2 weeks following the last ERT dose

• Boxed warnings for severe hypersensitivity reactions, infusion-associated reactions, and risk of acute cardiorespiratory failure in susceptible patients

• NDA approval 09/28/2023; Breakthrough Therapy, Orphan Drug, Standard Review

• Indicated in combination with cipaglucosidase alfa-atga (Pombiliti) for the treatment of adults with late-onset Pompe disease weighing ≥ 40 kg and who are not improving on their current ERT

• Enzyme stabilizer

• Oral capsule: 65 mg

• Recommended dosage is based on actual body weight administered every other week:

» Patients weighing ≥ 50 kg: 260 mg

» Patients weighing ≥ 40 kg to < 50 kg: 195 mg

• Capsules should be taken with an unsweetened beverage about 1 hour before the start of the Pombiliti infusion; do not consume other beverages or food for ≥ 2 hours prior to and 2 hours after taking

505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

Glossary:

AAP American Academy of Pediatrics

AChRab+ acetylcholine receptor antibody positive

ACIP Advisory Committee on Immunization Practices

ADR adverse drug reaction

BLA Biologics License Application

CDC Centers for Disease Control and Prevention

CI confidence interval

COVID-19 Coronavirus Disease 2019

ECG electrocardiogram

FDA Food and Drug Administration

G-CSF granulocyte-colony stimulating factor

GI gastrointestinal

HCP healthcare professional

HER2- human epidermal growth factor receptor 2 negative

HIV human immunodeficiency virus

HR+ hormone receptor positive

ICER Institute for Clinical and Economic Review

IM intramuscular

IV intravenous

JIA juvenile idiopathic arthritis

MDV multiple-dose vial

MMWR Morbidity and Mortality Weekly Report

mRNA messenger ribonucleic acid

NDA New Drug Application

NIH National Institutes of Health

NSCLC non-small cell lung cancer

OA osteoarthritis

OTC over-the-counter

R/R relapsed/refractory

RA rheumatoid arthritis

REMS Risk Evaluation and Mitigation Strategy

RNA ribonucleic acid

ROS1 ROS proto-oncogene 1, receptor tyrosine kinase

SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

SC subcutaneous

SDV single-dose vial

TNFα tumor necrosis factor-alpha

US United States

USP US Pharmacopeia

USPSTF US Preventive Services Task Force

WHO World Health Organization

COVID-19 Disclaimer: For the most current COVID-19 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.

Disclaimer: The content in this publication is not a substitute for professional medical advice. For questions regarding any medical condition or if you need medical advice, please contact your healthcare provider.

© 2023. Magellan Rx Management, a Prime Therapeutics LLC company. All rights reserved.