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
Devon Trumbower PharmD, BCPS
BEHAVIORAL HEALTH CORNER
COVID-19 NOTABLES
DRUG INFORMATION HAPPENINGS & HIGHLIGHTS
PIPELINE NEWS
RECENT FDA APPROVALS
Arexvy™, the first vaccine to prevent lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) has been approved by the US FDA for use in individuals ≥ 60 years of age. RSV-related LRTD can lead to life-threatening pneumonia and bronchiolitis in older adults and results in approximately 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths annually among US adults aged ≥ 65 years of age. Arexvy (RSV vaccine, adjuvanted) by GlaxoSmithKline is expected to be available prior to the 2023–2024 RSV season, which typically begins in late fall. The vaccine is administered as a single 120 mcg/0.5 mL IM dose. In an ongoing, randomized, phase 3, multinational, placebo-controlled trial (AReSVi-006; NCT04886596; n=24,966) in participants ≥ 60 years of age, vaccine efficacy was 82.6% (96.95% CI, 57.9 to 94.1) in preventing RSV-related LRTD after a median follow-up of 6.7 months. The most common ADRs were injection site pain, fatigue, myalgia, and headache. The FDA is requiring postmarketing reporting of Guillain-Barré syndrome and acute disseminated encephalomyelitis. The agency has also recently approved Pfizer’s RSV vaccine (Abrysvo™) for the same indication. Due to approval timing, details of Pfizer’s RSV vaccine were not included. ACIP is scheduled to provide recommendations on the RSV vaccines in June 2023.
An FDA advisory committee voted unanimously in favor of allowing OTC marketing of norgestrel (Opill), a progestinonly oral contraceptive by Perrigo. In a presentation to the panel, HRA Pharma/Perrigo, the manufacturer of the Rx version (not currently marketed) cited potential benefits of improved access to effective contraception and reduced unintended pregnancy that align with goals of the DHHS Healthy People 2030 initiative. Progestin-only oral contraceptives generally have less contraindications than combined estrogen-progestin pills with a similar failure rate (7%). The FDA cited outstanding safety concerns for individuals with undiagnosed/history of breast or other progestin-sensitive cancer, abnormal vaginal bleeding (undiagnosed etiology), and the potential for drug interactions (ulipristal emergency contraceptive). The FDA is expected to make a final decision on OTC approval of Perrigo’s Opill this summer.
The FDA approved brexpiprazole (Rexulti ®) for the treatment of agitation associated with dementia due to Alzheimer’s disease (AD). It is the first and only drug with this indication. The new indication carries a limitation of use stating it is not indicated as an as-needed treatment for agitation associated with AD dementia. Brexpiprazole is taken orally once daily and carries existing indications for the treatment of schizophrenia and adjunctive therapy for major depressive disorder.
The agency approved Otsuka’s aripiprazole (Abilify Asimtufii ® ), a long-acting injectable antipsychotic administered by IM injection once every 2 months by an HCP. The 960 mg/3.2 mL and 720 mg/2.4 mL single-dose prefilled syringes are approved to treat schizophrenia and as maintenance monotherapy to treat bipolar I disorder in adults. Approval was partially based on data from trials of aripiprazole (Abilify Maintena®) which shares the same indications and is administered once monthly as an IM injection by an HCP.
Teva’s risperidone (Uzedy™), a long-acting injectable antipsychotic, received FDA approval for the treatment of schizophrenia in adults. The ER injectable suspension was approved as 50 mg/0.14 mL, 75 mg/0.21 mL, 100 mg/0.28 mL, 125 mg/0.35 mL, 150 mg/0.42 mL, 200 mg/0.56 mL, and 250 mg/0.7 mL single-dose prefilled syringes. Following a trial of oral risperidone to establish tolerability, Uzedy is administered as a SC injection by an HCP once monthly or once every 2 months.
The FDA has approved nirmatrelvir/ritonavir copackaged tablets (Paxlovid™) for mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. FDA’s VRBPAC will meet on June 15, 2023 to discuss and make recommendations on the selection of strain(s) to include in the COVID-19 vaccine composition for the 2023–2024 vaccination campaign. The WHO announced that COVID-19 no longer constitutes a public health emergency of international concern. WHO’s focus will transition to long-term management of the SARS-CoV-2 pandemic. Please refer to the COVID-19 disclaimer at the end of the publication.
• Teva initiated a voluntary recall of 13 lots of various strengths of fentanyl buccal tablets to the consumer level. The recalled lots, which are labeled under Mayne Pharma, contain product inserts/medication guides that are missing safety updates.
• Elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta®) received approval for expansion of the indication for the treatment of cystic fibrosis (CF) with ≥ 1 CFTR F508del gene mutation or a responsive CFTR mutation to include pediatric patients 2 to 5 years of age. Previously, Trikafta was indicated in patients ≥ 6 years of age. The FDA also approved an oral granule formulation (supplied in morning and evening unit-dose packets) to accommodate weight-based dosing in the younger age group.
• The FDA approved ivacaftor (Kalydeco®) for use in pediatric patients aged 1 to < 4 months of age with CF and ≥ 1 responsive CFTR gene mutation. Two additional strengths of oral granules, 5.8 mg and 13.4 mg, were also approved to accommodate dosing in patients aged < 4 months of age. Kalydeco 150 mg tablets and 25 mg, 50 mg, and 75 mg oral granules were previously approved for patients ≥ 4 months old.
• Due to bankruptcy, Akorn has voluntarily recalled dozens of human products as the company will no longer be able to ensure strength, quality, and purity standards via its quality program. Product remaining on the market should not be used, and Akorn is requesting the recalled products be destroyed.
• An alternate initial dosing regimen (loading dose) for initiation of lacosamide (Vimpat®) was approved for the treatment of patients aged ≥ 1 month of age to < 17 years of age with partial onset seizures and in patients aged ≥ 4 years of age to < 17 years of age with primary generalized tonic-clonic seizures. The alternate dosing regimen is continued for 1 week and is intended to achieve the recommended maintenance dose in a shorter timeframe. An alternate initial dosing regimen for adults was previously approved.
• The FDA approved a new 45 mg 6-month dosing regimen for leuprolide acetate for depot suspension (Lupron Depot-Ped®) for the treatment of pediatric patients with central precocious puberty (CPP). A 45 mg prefilled syringe was approved for administration of the IM dose by an HCP. Existing prefilled syringe strengths are approved for 1-month or 3-month administration for CPP.
• Novo Nordisk’s semaglutide (Wegovy®) availability is limited for the 0.25 mg/0.5 mL, 0.5 mg/0.5 mL, and 1 mg/0.5 mL prefilled pens through September 2023.
• The FDA has released a Drug Safety Communication detailing updates to the boxed warning and other sections of product labeling for amphetamine and methylphenidate stimulants regarding the risk for misuse, abuse, addiction, and overdose with these medications to ensure consistency in labeling across the entire class of these medicines.
• Due to expiration of the COVID-19 public health emergency (PHE) on May 11, 2023, the DEA and SAMHSA issued a temporary extension (for 6 months – until November 11, 2023) of telemedicine flexibilities for prescription of controlled medications that were initiated during the COVID-19 PHE. Additionally, any practitioner-patient telemedicine relationships that have been/will be established up until November 11, 2023, will be extended for 1 year (until November 11, 2024).
• The American Urological Association (AUA) and Society of Urologic Oncology (SUO) released a guideline on the diagnosis and management of non-metastatic upper tract urothelial carcinoma.
• The American College of Radiology (ACR) has updated recommendations on breast cancer screening for women at higher-than-average risk.
natalizumab (biosimilar to Biogen’s Tysabri®) Polpharma/Sandoz
ritlecitinib Pfizer
rozanolixizumab
tocilizumab (biosimilar to Genentech’s Actemra®) Fresenius Kabi
• IL-17 antagonist
• IV
• Anti-alpha-4-integrin antibody
efgartigimod/ hyaluronidase Argenx
methotrexate Aldeyra
gepirone GlaxoSmithKline
adalimumab (biosimilar to Humira®) Alvotech
carbidopa/levodopa ER Amneal
valoctocogene roxaparvovec Biomarin
• Oral
• JAK inhibitor/TEC kinase inhibitor Alopecia areata (ages ≥ 12 years of age)
• SC • FcRn antagonist
• IV, SC
• IL-6 receptor antagonist
JIA; Systemic JIA
• Oral
• Pyrimidine synthesis inhibitor
• SC
• FcRn antagonist
• Intravitreal
• Folate analog metabolic inhibitor
• Oral
• Serotonin 1A receptor antagonist
• SC
• TNF-alpha inhibitor
• Oral
• Aromatic amino acid decarboxylation inhibitor/Dopamine receptor agonist
• IV
• Gene therapy
RA; AS; PsO; PsA; JIA; CD; UC – for interchangeability
A
niraparib (Zejula®)
GlaxoSmithKline
sildenafil (Liqrev®) CMP
sodium oxybate (Lumryz™) Avadel CNS
• NDA approval 04/26/2023; Orphan Drug, Standard Review
• Indicated for:
» Maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to 1st-line platinum-based chemotherapy
» Maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy; select patients based on an FDA-approved companion diagnostic
• Poly (ADP-ribose) polymerase (PARP) inhibitor
• Oral tablet: 100 mg, 200 mg, 300 mg; 100 mg oral capsule previously approved for these uses
• Recommended dosage with or without food is:
» 1st-line maintenance treatment of advanced ovarian cancer: 200 mg once daily for patients < 77 kg (< 170 lbs) or platelet count < 150,000/mcL; 300 mg once daily for patients ≥ 77 kg (≥ 170 lbs) and platelet count ≥ 150,000/mcL
» Maintenance treatment of recurrent germline BRCA-mutated ovarian cancer: 300 mg once daily
• 505(b)(2) NDA approval 04/28/2023; Standard Review
• Indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening
• Phosphodiesterase-5 (PDE-5) inhibitor
• Oral suspension: 10 mg/mL; 1 mL contains 10 mg of sildenafil which is equivalent to 14 mg of sildenafil citrate
• Recommended dosage is 20 mg taken 3 times daily
• 505(b)(2) NDA approval 05/01/2023; Orphan Drug, Standard Review
• Indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy
• Central nervous system (CNS) depressant
• ER oral suspension: 4.5 g, 6 g, 7.5 g, 9 g packets
• Recommended dosage is initiated at 4.5 g once per night ≥ 2 hours after eating; titrate to effect in 1.5 g increments per night at weekly intervals to a recommended dosage range of 6 g to 9 g once per night at bedtime; dose is prepared by suspending in 1/3 cup of water in provided mixing cup
• Boxed warnings for CNS depression and abuse/misuse; schedule III controlled substance
• Only available through a REMS program
lacosamide (Motpoly XR™)
Aucta
tropicamide/ phenylephrine HCl (Mydcombi®)
Eyenovia
pegunigalsidase alfa-iwxj (Elfabrio®)
Chiesi
• 505(b)(2) NDA approval 05/04/2023; Standard Review
• Indicated for the treatment of partial-onset seizures (POS) in adults and pediatric patients weighing ≥ 50 kg
• Anticonvulsant
• ER oral capsule: 100 mg, 150 mg, 200 mg
• Recommended initial dosage in pediatric patients weighing ≥ 50 kg for POS is 100 mg once daily; in adults (≥ 17 years of age), the initial dose for monotherapy for POS is 200 mg once daily and the initial dose for adjunctive therapy is 100 mg once daily (maximum dose for adults is 400 mg once daily); for both age ranges, the dosage is increased based on response and tolerability, no more frequently than once per week
• Schedule V controlled substance
• 505(b)(2) NDA approval 05/05/2023; Standard Review
• Indicated to induce mydriasis for diagnostic procedures and in conditions where short-term pupil dilation is desired
• Anticholinergic/alpha-1 adrenergic receptor agonist
• Ophthalmic spray: tropicamide 1% and phenylephrine HCl 2.5% metered spray delivering 0.008 mL containing 0.08 mg tropicamide and 0.2 mg phenylephrine HCl
• Recommended dosage is 1 metered spray to the cornea of each eye to be dilated; repeat after 5 minutes; in pediatric patients < 1 year of age, administer 1 metered spray to the cornea of each eye to be dilated, up to a maximum of 3 sprays per eye per day
• Product availability is expected in summer 2023 with a full launch in 2024
• BLA approval 05/09/2023
• Indicated for the treatment of adults with confirmed Fabry disease
• Hydrolytic lysosomal neutral glycosphingolipid-specific enzyme
• Solution for injection: 20 mg/10 mL (2 mg/mL) in an SDV
• Recommended dosage is 1 mg/kg (based on actual body weight) every 2 weeks administered as an IV infusion by an HCP; the initial recommended infusion rates are also based on actual body weight; during administration, medical support measures (e.g., cardiopulmonary resuscitation equipment) should be available; dosage/administration modifications may be required due to hypersensitivity reactions or infusion-associated reactions; under the supervision of an HCP, home administration may be considered for patients who have an infusion duration that is well tolerated
• For enzyme-replacement therapy (ERT)-naïve patients, before administration, consider premedication with antihistamines, antipyretics, and/or corticosteroids; for ERTexperienced patients, consult the prescribing information for premedication recommendations
• Boxed warning for hypersensitivity reactions, including anaphylaxis
zolpidem tartrate (no trade name)
Almatica
fezolinetant (Veozah™)
Astellas
perfluorohexyloctane (Miebo™)
Bausch and Lomb
• 505(b)(2) NDA approval 05/09/2023; Standard Review
• Indicated for the short-term treatment of transient insomnia characterized by difficulties with sleep initiation in adults < 65 years of age
• Gamma-aminobutyric acid (GABA) A receptor positive modulator
• Oral capsule: 7.5 mg; if a 5 mg or 10 mg dosage is needed, another zolpidem tartrate immediate-release (IR) product should be used
• Recommended starting dosage in females is 5 mg once nightly; as a result, use another zolpidem IR product for dosage initiation in these patients; males can initiate zolpidem at a dose of 5 mg IR, 7.5 mg IR, or 10 mg IR once nightly; for males and females, if a 5 mg dosage is not effective, the dose can be increased to 7.5 mg or 10 mg once nightly (maximum recommended dosage of 10 mg IR once nightly); the lowest effective dosage should be utilized for short-term use only with the dosage taken once per night right before bedtime with ≥ 7 to 8 hours remaining before planned awakening
• Boxed warning for complex sleep behaviors; schedule IV controlled substance
• NDA approval 05/12/2023; Priority Review
• Indicated for the treatment of moderate to severe vasomotor symptoms due to menopause
• Neurokinin 3 (NK3) receptor antagonist
• Oral tablet: 45 mg
• Recommended dosage is 45 mg once daily with or without food; hepatic function (serum ALT, serum AST, and serum bilirubin [total and direct]) should be assessed at baseline and at 3 months, 6 months, and 9 months following initiation as well as if symptoms occur that are suggestive of liver injury
• NDA approval 05/18/2023; Standard Review
• Indicated for the treatment of signs and symptoms of dry eye disease
• Semifluorinated alkane
• Ophthalmic solution: 100% perfluorohexyloctane
• Recommended dosage is 1 drop into each eye 4 times daily
• Product availability is expected in the 2H of 2023 beremagene geperpavec-svdt (Vyjuvek™)
Krystal Biotech
• BLA approval 05/19/2023; Fast Track, Orphan Drug, Priority Review, Regenerative Medicine Advanced Therapy
• Indicated for topical treatment of wounds in patients ≥ 6 months old with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene
• Herpes-simplex virus type 1 (HSV-1) vector-based gene therapy
• Biological suspension: 5 x 10⁹ plaque forming units (PFUs)/mL that is mixed into an excipient gel prior to topical application
• Recommended dosage is to apply weekly by an HCP in a healthcare setting (e.g., clinic) or at home, with dosing based on patient’s age and size of the wound; applied until wound closure
• Product availability is expected in the 3Q of 2023
epcoritamab-bysp (Epkinly™)
Genmab
somapacitan-beco (Sogroya®)
Novo Nordisk
• BLA approval 05/19/2023; Accelerated Approval, Assessment Aid, Priority Review
• Indicated for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥ 2 lines of systemic treatment; continued approval for this use may require demonstration of benefit in confirmatory clinical trials
• Bispecific CD20-directed CD3 T-cell engager
• Solution for injection: 4 mg/0.8 mL (must be diluted) and 48 mg/0.8 mL in SDVs
• Recommended dosage involves step-up dosing for cycle 1 (0.16 mg on day 1; 0.8 mg on day 8; 48 mg on day 15 and day 22), followed by fixed dosing of 48 mg, administered weekly during cycles 2 and 3, every other week during cycle 4 through 9, and then every 4 weeks for cycle 10 and beyond; administered SC by a qualified HCP with medical support to manage severe reactions such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS); administered in 28-day cycles until disease progression or unacceptable toxicity; patients should be hospitalized for 24 hours following administration of the cycle 1 day 15 dose of 48 mg; premedication and prophylaxis should be administered as described in the prescribing information; dosage modifications, including withholding or permanently discontinuing therapy, may be required depending on the ADR and severity
• Boxed warning for CRS and ICANS
• sBLA approval 04/28/2023
• New indication for the treatment of growth failure due to inadequate secretion of endogenous growth hormone (GH) in pediatric patients ≥ 2.5 years of age; already indicated for replacement of endogenous GH in adults with GH deficiency
• Human growth hormone analog
• Ready-to-use liquid solution: new pediatric 15 mg/1.5 mL (10 mg/mL) prefilled pen; existing formulations include 5 mg/1.5 mL (3.3 mg/mL) and 10 mg/1.5 mL (6.7 mg/mL) prefilled pens
• Recommended pediatric dosage is weight-based starting at 0.16 mg/kg once weekly for treatment-naïve patients or those switching from daily growth hormone; dosage is individualized based on the growth response for each patient
505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.
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.
Glossary:
ACIP Advisory Committee on Immunization Practices
ADR adverse drug reaction
ALT alanine aminotransferase
AS ankylosing spondylitis
AST aspartate aminotransferase
BLA Biologics License Application
BRCA BReast CAncer gene
CD Crohn’s disease
CDC Centers for Disease Control and Prevention
CFTR cystic fibrosis transmembrane conductance regulator
CI confidence interval
COVID-19 Coronavirus Disease 2019
DEA Drug Enforcement Administration
DHHS Department of Health and Human Services
ER extended-release
F508del phenylalanine at residue 508
FcRn fragment crystallizable receptor
FDA Food and Drug Administration
H half
HCl hydrochloride
HCP healthcare professional
IL-17 interleukin-17
IL-6 interleukin-6
IM intramuscular
IV intravenous
JAK Janus kinase
JIA juvenile idiopathic arthritis
MS multiple sclerosis
n number of participants
NCT national clinical trial
NDA New Drug Application
NIH National Institutes of Health
OTC over-the-counter
PsA psoriatic arthritis
PsO plaque psoriasis
References: cdc.gov fda.gov who.int federalregister.gov nejm.org
Q quarter
RA rheumatoid arthritis
REMS Risk Evaluation and Mitigation Strategy
RSV respiratory syncytial virus
Rx prescription
SAMHSA Substance Abuse and Mental Health Services Administration
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
sBLA supplemental Biologics License Application
SC subcutaneous
SDV single-dose vial
TEC tyrosine kinase expressed in hepatocellular carcinoma
TNF tumor necrosis factor
UC ulcerative colitis
US United States
VRBPAC Vaccines and Related Biological Products Advisory Committee
WHO World Health Organization
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.