Clinical Highlights: September 2024 - Prime Therapeutics
Clinical Highlights: September 2024
Your monthly source for drug information highlights.
The Centers for Disease Control and Prevention (CDC) has published recommendations from the Advisory Committee on Immunization Practices (ACIP) for the 2024–2025 influenza season. Annual influenza vaccination is recommended for all individuals at least six months of age who do not have contraindications, ideally during September or October. Trivalent inactivated, trivalent recombinant, and trivalent live attenuated influenza vaccines are anticipated to be available. Individuals are recommended to receive an influenza vaccine FDA-approved for their age range; however, solid organ transplant recipients between the ages of 18 and 64 years old currently receiving immunosuppressive medications can receive either a high-dose inactivated influenza vaccine or an adjuvanted inactivated influenza vaccine (no preference over other age-appropriate trivalent inactivated or trivalent recombinant influenza vaccines). In general, no preferential recommendation for a specific vaccine is made except for adults ≥ 65 years of age for whom the higher dose or adjuvanted influenza vaccine are preferentially recommended (e.g., trivalent high-dose inactivated, trivalent recombinant or trivalent adjuvanted inactivated influenza vaccines). The American Academy of Pediatrics (AAP) has published 2024–2025 recommendations for influenza prevention and also recommends everyone at least six months of age, who do not have a contraindication, receive the annual influenza vaccination, preferably by Oct. 31. Children six months through eight years of age who are receiving an influenza vaccine for the first time or who only received one dose before July 1, 2024, should receive two doses of influenza vaccine at least four weeks apart; this is also recommended for children with an unknown influenza vaccination status. All other children are recommended to receive one dose this season.
The U.S. Food & Drug Administration (FDA) has approved and authorized emergency use for updated mRNA COVID-19 vaccines to include a monovalent component that targets the Omicron variant KP.2 strain of SARS-CoV-2. The updated 2024–2025 formula mRNA vaccines include COVID-19 Vaccine, mRNA (Comirnaty) and COVID-19 Vaccine, mRNA (Spikevax) (both FDA-approved for persons ≥ 12 years old) as well as Moderna and Pfizer/BioNTech COVID-19 vaccines (both authorized for emergency use in patients six months to 11 years old). The FDA has also granted EUA to the Novavax COVID-19 vaccine, adjuvanted (2024–2025 formula) to include a monovalent component corresponding to the Omicron variant JN.1 strain for use in individuals aged ≥ 12 years old. The updated 2024–2025 vaccine formulas more closely align with circulating variants providing enhanced protection from serious COVID-19 complications (e.g., hospitalization, death). The CDC has published a Morbidity and Mortality Weekly Report (MMWR) on ACIP recommendations for use of COVID-19 vaccines for 2024 to 2025, and the updated 2024–2025 formula COVID-19 vaccines are recommended for all individuals at least six months of age to provide protection against severe COVID-19-associated illness as well as death from currently circulating SARS-CoV-2 strains.
The FDA has revised the EUA for the SARS-CoV-2 spike protein-directed attachment inhibitor pemivibart (Pemgarda) to limit use to when the combined national frequency of variants with substantially decreased susceptibility to the agent is ≤ 90%. Pemgarda is authorized for emergency use for the pre-exposure prophylaxis of COVID-19 in individuals ≥ 12 years of age weighing ≥ 40 kg, who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2 and who: (1) have moderate-to-severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and (2) are unlikely to mount an adequate immune response to COVID-19 vaccination. Pemgarda is not FDA-approved for any use, including for preexposure prophylaxis of COVID-19.
At the end of September 2024, U.S. households will be able to order four free COVID-19 tests through covidtests.gov.
Eli Lilly and Company (Lilly) has released single-dose vials (SDVs) of the glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 receptor agonist obesity drug, tirzepatide (Zepbound), for self-pay patients with an on-label prescription. The 2.5 mg and 5 mg vials will be distributed through LillyDirect’s self-pay channel and carry a list price that is at least 50% lower than that of other similar GLP-1 medications for obesity. Ancillary supplies (e.g., syringes, needles) can also be purchased and instructional materials for administering the medication will be available. Zepbound is also available in a single-dose autoinjector providing 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 mL doses.
A case-control designed disproportionality analysis utilizing the WHO global database published in JAMA Network Open described a signal of semaglutide-associated suicidal ideation. The WHO global individual case safety reports database is the largest pharmacovigilance archive worldwide with over 28 million reports of suspected adverse drug reactions (ADRs) from 140 member countries. A comprehensive search for reports of suicidal or self-injurious ADRs revealed a total of 107 and 162 cases of suicidal and/or self-injurious ADRs between November 2000 and August 2023 with semaglutide and liraglutide, respectively, with significant disproportionality detected only for semaglutide-associated suicidal ideation compared with all medications (reporting odds ratio, 1.45; 95% confidence interval, 1.18 to 1.77).
Lilly has announced topline results from the three-year SURMOUNT-1 study (n=1,032) conducted in adults with pre-diabetes and obesity or overweight. Data demonstrated sustained weight loss with an average of 22.9% reduction in body weight from baseline with tirzepatide (Zepbound and Mounjaro) 15 mg weekly compared to 2.1% with placebo. Furthermore, a 94% decrease in the risk of progression to type 2 diabetes mellitus (T2DM) with tirzepatide (pooled doses of 5 mg, 10 mg, and 15 mg) compared to placebo was observed.
Shortage Updates
Eli Lilly’s tirzepatide (Zepbound) is reported as currently available in all strengths, as is the T2DM formulation of tirzepatide (Mounjaro). Additionally, all strengths of Novo Nordisk’s semaglutide (Ozempic) formulation for select patients with T2DM are available, along with all strengths, except for the 0.25 mg strength, of the semaglutide product indicated for weight management (Wegovy). Novo Nordisk’s liraglutide (Saxenda) has limited availability, as does the liraglutide (Victoza) formulation indicated for select patients with T2DM; an authorized generic of Victoza distributed by Teva is available. The GLP-1 receptor agonist dulaglutide (Trulicity), indicated for select patients with T2DM, is available in all strengths.
Two of the three strengths of penicillin G benzathine (Bicillin L-A) are available with the remaining strength having an estimated recovery of March 2025. The shortage of this antibiotic is due to increased demand for the drug. The FDA continues to allow temporary importation of benzathine benzylpenicillin (Extencilline) and temporary importation of benzathine benzylpenicillin tetrahydrate (Lentocilin) to mitigate the shortage. Both imported products are available.
Shortages of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) continue to be reported. Availability of generic methylphenidate HCl extended-release (ER) tablets is variable depending on the manufacturer. Brand-name Relexxii from Vertical, as well as brand-name Concerta from Janssen, are currently available. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages continue to improve, and brand-name Adderall IR tablets from Teva are available. Shortages of the generic version of Vyvanse, lisdexamfetamine dimesylate capsules and chewable tablets persist. Brand-name Vyvanse capsules and chewable tablets remain available from Takeda. To address the lisdexamfetamine shortage, the DEA increased production limits for lisdexamfetamine by nearly 24%.
Drug Information Highlights
Pfizer has announced the voluntary withdrawal of all lots of the sickle cell disease therapy voxelotor (Oxbryta) and discontinuation of all active clinical trials for the drug. The withdrawal is based on clinical data that suggest an increase in vaso-occlusive crises and fatal events with Oxbryta that necessitate further evaluation.
The FDA has issued a Drug Safety Communication warning of rare occurrences of serious liver injury with fezolinetant (Veozah), an oral neurokinin 3 (NK3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. The new safety concern has been added to the existing warning in the labeling about hepatic transaminase elevation; patients should stop Veozah immediately and contact an HCP if signs or symptoms of liver injury occur. The frequency of hepatic laboratory tests has been increased, and the prescribing information now recommends monthly testing for two months after initiation; testing should also occur at months three, six and nine (already recommended).
The CDC has published interim clinical considerations for use of the Smallpox and Monkeypox Vaccine, Live, Nonreplicating (Jynneos) for mpox prevention; Jynneos is FDA-approved for prevention of smallpox and mpox in adults determined to be at high risk for these infections. People at risk of mpox should ideally be vaccinated prior to exposure to mpox virus, but the vaccine can also be used post-exposure to prevent infection. Jynneos has been the predominant vaccine used in the U.S., but Smallpox and Mpox (Vaccinia) Vaccine, Live (ACAM2000) is also indicated for active immunization for the prevention of smallpox and mpox disease in individuals determined to be at high risk for these infections; however, this vaccine has more adverse effects and contraindications.
The FDA has expanded use of Insulet's SmartAdjust technology utilized by Insulet's Omnipod 5 Automated Insulin Delivery System to include management of T2DM in adults. Previously, the interoperable automated glycemic controller (SmartAdjust Technology) was only indicated for the management of type 1 diabetes mellitus (T1DM) in ages ≥ 2 years old. The SmartAdjust technology software automatically adjusts insulin delivery through a connection to an alternate controller-enabled insulin pump and integrated continuous glucose monitor (iCGM).
The FDA's Cardiovascular and Renal Drugs Advisory Committee will convene on Oct. 10, 2024 to discuss the new drug application (NDA) for elamipretide by Stealth Bio. Elamipretide injection is an investigational agent for the treatment of Barth Syndrome, a rare condition characterized by dilated cardiomyopathy, skeletal myopathy, neutropenia and short stature that predominantly affects men.
Drug Information Happenings
The CDC has published updated recommendations from ACIP in the MMWR on the use of respiratory syncytial virus (RSV) vaccines in adults ≥ 60 years old. In June 2024, ACIP voted in favor of all adults ≥ 75 years of age as well as adults aged 60 to 74 years who are at increased risk for severe RSV disease to receive a single dose of RSV vaccine.
The Institute for Clinical and Economic Review (ICER) has released its final evidence report on imetelstat (Rytelo) for the treatment of anemia in patients with low-to-intermediate risk myelodysplastic syndrome (MDS). A majority of panelists voted that current evidence is inadequate to show a net health benefit for imetelstat plus best supportive care compared to best supportive care alone in patients with lower risk MDS without the del(5q) mutation who are transfusion dependent and ineligible for, or refractory to erythropoiesis-stimulating agents (ESAs). Furthermore, all panelists voted that current evidence is inadequate to show a net health benefit for imetelstat plus best supportive care when compared to luspatercept-aamt (Reblozyl) plus best supportive care in patients with lower risk MDS without the del(5q) mutation who are transfusion dependent and ineligible for, or refractory to ESAs, and are ring sideroblast positive.
The U.S. Preventive Services Task Force (USPSTF) has issued final recommendations on screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy. The USPSTF concludes that for asymptomatic pregnant adolescents and adults, evidence is insufficient to recommend for or against screening for iron deficiency and iron deficiency anemia, and evidence is insufficient to determine the benefits versus harms of routine iron supplementation in pregnant patients for prevention of adverse maternal and infant health outcomes.
The American College of Gastroenterology (ACG) has published new recommendations for the treatment of Helicobacter pylori (H. pylori) infection in North America. In addition to providing recommendations for treatment-naïve and treatment-experienced patients, the guidelines detail who to test, the need for universal post-treatment test-of-cure, as well as evidence on antibiotic susceptibility testing and its role in determination of initial and salvage treatment.
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 health care provider.
All brand names are property of their respective owners.
COVID-19 = coronavirus 2019
DEA = Drug Enforcement Administration
EUA = emergency use authorization
GLP-1 = glucagon-like peptide-1
HCl = hydrochloride
Editor-In-Chief: Maryam Tabatabai, PharmD
Executive Editor: Anna Schreck Bird, PharmD
Deputy Editors: Erik Hamel, PharmD; Olivia Pane, PharmD, CDCES
