Clinical Highlights: April 2025 - Prime Therapeutics
Clinical Highlights: April 2025
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Results from the double-blind, placebo-controlled SOUL trial (n=9,650) have been published in The New England Journal of Medicine. After a median follow-up of 49.5 months, oral semaglutide (Rybelsus) 14 mg daily was associated with a significantly lower risk of major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) versus placebo (hazard ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; p=0.006) in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease, chronic kidney disease or both. Novo Nordisk has also announced results from the 52-week, Phase 3b STRIDE trial (n=792) in which semaglutide (Ozempic) 1 mg subcutaneous (SC) weekly demonstrated a statistically significant improvement in maximum walking distance by 13% versus placebo (p=0.0004) in adults with T2DM and symptomatic peripheral artery disease (PAD). At 52 weeks, the median treatment difference favoring semaglutide was 26.4 meters (95% CI, 11.8 to 40.9) on a 12% incline. Based on these results, Novo Nordisk has submitted a label extension application to the United States (U.S.) Food and Drug Administration (FDA) for Ozempic; a decision is expected in 2025.
A multicenter, randomized, open-label, Phase 4 study (SURPASS-SWITCH; n=282), published in the Annals of Internal Medicine, evaluated adults with hemoglobin A1c (HbA1c) between 7% to ≤ 9.5%, a stable body weight and a body mass index (BMI) of ≥ 25 kg/m2 who had been receiving a stable dose of dulaglutide (0.75 mg or 1.5 mg) for at least six months and zero to three oral antihyperglycemic medications. Patients were randomized to either switch to tirzepatide or escalate the dulaglutide dose to 4.5 mg or the maximum tolerated dose (MTD). At week 40, the primary endpoint of change from baseline in HbA1c was significantly improved with switching to tirzepatide 15 mg or MTD (-1.44%) compared to escalation of dulaglutide (-0.67%) (estimated treatment difference, -0.77%; 95% CI, -0.98% to -0.56%; p<0.001). Furthermore, the key secondary endpoint of change from baseline in weight at week 40 was also significantly improved with tirzepatide (-10.5 kg) compared with dulaglutide (-3.6 kg) (estimated treatment difference, -6.9 kg; CI, -8.3 to -5.5 kg; p<0.001).
A systematic review and meta-analysis published in JAMA Neurology evaluated the potential for cardioprotective glucose-lowering agents (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 agonists [GLP-1s], metformin and pioglitazone) to reduce the risk of dementia across 23 randomized clinical trials (n=160,191). A significant association between cardioprotective glucose-lowering therapy and decreases in cognitive impairment or dementia was not found (odds ratio [OR], 0.83; 95% CI, 0.6 to 1.14); however, GLP-1s were associated with a statistically significant decrease in dementia (OR, 0.55; 95% CI, 0.35 to 0.86) whereas SGLT2is were not (OR, 1.2; 95% CI, 0.67 to 2.17). According to the authors, the larger risk reduction observed with GLP-1s could potentially be attributed to differences in populations enrolled, as there was a higher all-cause dementia event rate in the control group of GLP-1 trials compared with SGLT2i trials (0.14% versus 0.05%) which led to an increase in statistical power to detect associations.
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The U.S. Government Accountability Office (GAO) has published a report on drug shortages. The GAO provides recommendations for the Department of Health and Human Services (HHS) to collaborate with the FDA and other agencies to help mitigate this serious public health issue. Although the annual number of drug shortages has primarily decreased since the beginning of the coronavirus 2019 disease (COVID-19) pandemic, drug shortages are lasting longer.
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Shortages of the following GLP-1s are being reported by the FDA as resolved: Novo Nordisk’s semaglutide (Ozempic, Wegovy) and Eli Lilly’s tirzepatide (Mounjaro, Zepbound). Novo Nordisk’s liraglutide (Saxenda) for weight management has limited availability due to increased demand for the drug, and liraglutide (Victoza), the formulation indicated for select patients with T2DM, has limited availability due to a delay in shipping of the drug; an authorized generic of Victoza distributed by Teva is available. A generic version of Victoza from Hikma will be available upon release of the product from the manufacturer; Meitheal also has generic product available. Eli Lilly’s dulaglutide (Trulicity) is currently available. Following notification from Novo Nordisk that several hundred units of counterfeit Ozempic 1 mg were in the U.S. drug supply chain, the FDA seized the counterfeit product and issued a statement on the counterfeit product. Patients, wholesalers, pharmacies and health care professionals are instructed to check Ozempic products and not use, distribute or sell those labeled with lot number PAR0362 and illegitimate serial numbers starting with the first eight digits 51746517. According to Novo Nordisk, lot number PAR0362 is an authentic lot number but when this is coupled with the aforementioned eight digits, it is counterfeit and should not be used. The FDA’s investigation of the counterfeit product is ongoing.
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Shortages of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) continue to be reported. Availability of generic methylphenidate hydrochloride (HCl) extended-release (ER) tablets is variable depending on the manufacturer. Brand name Relexxii from Vertical has limited availability due to increased demand; brand name Concerta from Janssen is currently available. Methylphenidate ER film (Daytrana, generics) has limited availability or is unavailable due to shortage of an active ingredient. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate and dextroamphetamine sulfate immediate release (IR) tablet shortages are also being reported; all strengths of 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.
Data published in Diabetes, Obesity and Metabolism describe the rise in prevalence of obesity among youth and adults with type 1 diabetes mellitus (T1DM) from 2008–2011 to 2020–2023. In youth with T1DM, the prevalence of obesity rose from 18.1% to 26% during this timeframe and for adults with T1DM the increase was from 30.5% to 38.1%. Furthermore, over the 15-year timeframe, prescriptions for GLP-1 medications significantly rose across all BMI categories for these patients in a dose-response manner.
Sarepta provided an update on findings from the independent data monitoring committee (DMC) following the March 2025 safety communication on an acute liver failure fatality observed in a patient who had received delandistrogene moxeparvovec-rokl (Elevidys), an adeno-associated virus vector-based gene therapy indicated for select patients with Duchenne muscular dystrophy (DMD). While evaluation of the fatality continues, recruitment and dosing in certain clinical studies are temporarily on hold. However, as of early April, the committee concluded the overall benefit-to-risk profile remains positive for continuation of dosing in the clinical trials that have been paused; at this time, no protocol changes will be made.
The U.S. Centers for Disease Control and Prevention (CDC) reports, as of April 25, 2025, there were 884 confirmed cases of measles. Cases include 266 in individuals < 5 years of age, 338 in those 5 to 19 years of age, 261 in those ≥ 20 years of age and 19 with unknown age. The vast majority (97%) of cases are among individuals with unvaccinated or unknown vaccination status.
The FDA has granted marketing authorization to the first over the counter, at-home diagnostic test for chlamydia, gonorrhea and trichomoniasis. The Visby Medical Women’s Sexual Health Test is a single-use test intended for females with or without symptoms of these sexually transmitted infections (STIs). The test includes a collection kit (self-collected vaginal swab) and a powered testing device that communicates to the Visby Medical Application (app); the app displays results when the test is complete within approximately 30 minutes.
American College of Physicians (ACP) has published a guideline on pharmacologic treatments for acute episodic migraine headache in the outpatient setting. A triptan is recommended to be added to a non-steroidal anti-inflammatory drug (NSAID) to treat moderate to severe acute episodic migraine headache for nonpregnant adults who do not have a sufficient response to an NSAID (strong recommendation, moderate-certainty evidence). It is suggested to add a triptan to acetaminophen (APAP) for the treatment of moderate to severe acute episodic migraine headache for nonpregnant adults who do not have a sufficient response to APAP (conditional recommendation, low-certainty evidence).
The Institute for Clinical and Economic Review (ICER) published its final evidence report on effectiveness and value of suzetrigine (Journavx) for acute pain. ICER rates the evidence for suzetrigine for the treatment of acute pain in comparison with (1) no systemic treatment, (2) opioid analgesics and (3) NSAIDs as promising but inconclusive (P/I). As a sodium channel Naᵥ 1.8 inhibitor, suzetrigine has a novel mechanism of action (MOA) devoid of the potential for development of opioid use disorder that opioid analgesics carry; however, as with any novel therapy with a new MOA, questions remain regarding unknown harms. Concerns regarding acute renal injury and increased risk for cardiac arrhythmias given inhibition of Naᵥ 1.8 elicit the need for real world safety data to further delineate suzetrigine’s role in acute pain management.
ICER, in collaboration with researchers from Brown University, has published a white paper on strategies to ensure affordable and equitable access to GLP-1 obesity medications. The paper includes background on these medications as well as pipeline and pricing implications; potential market strategies (e.g., temporary coverage denial, enhanced prior authorization and formulary management, provider network management, innovative payment arrangements, carve-out programs for obesity management services), and potential federal policy interventions. The analysis is based on data from a targeted literature review and information gathered from interviews with various stakeholders (e.g., pharmacy benefit managers, manufacturers, patient advocacy groups, benefit consultants, state/Medicaid experts).
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Executive Editor: Anna Schreck Bird, PharmD
Deputy Editor: Olivia Pane, PharmD, CDCES