Clinical Highlights: November 2024 - Prime Therapeutics
Clinical Highlights: November 2024
Your monthly source for drug information highlights.
A retrospective propensity score-matched cohort study published in JAMA Pediatrics (n=6,912) utilized electronic health records from the TriNetX global federated network from Dec. 2019 to Jun. 2024 to assess the impact of GLP-1 receptor agonists on suicidal ideation or attempts in adolescents 12 to 18 years of age with a diagnosis of obesity. Data from 120 health care organizations, mainly in the U.S., were used for the assessment and subjects had either an anti-obesity GLP-1 receptor agonist prescription or evidence of lifestyle intervention without GLP-1 receptor agonist medication within the following year. In the GLP-1 receptor agonist cohort, 4,052 adolescents with obesity and a concomitant anti-obesity intervention were included. These individuals were propensity score-matched from 50,112 individuals in the control cohort yielding 3,456 participants in each balanced cohort. Overall, a GLP-1 receptor agonist prescription was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up compared with the control cohort (1.45% versus 2.26%, respectively; hazard ratio [HR], 0.67; p=0.02). A prescription for a GLP-1 receptor agonist was associated with a higher rate of gastrointestinal symptoms (6.9% versus 5.4%; HR, 1.41; p=0.003). This cohort study suggests favorable psychiatric safety for GLP-1 receptor agonists for weight loss in adolescents with obesity.
A retrospective cohort study published in Addiction analyzed electronic health record data and found an association between prescriptions for GIP and/or GLP-1 agents and lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. The study was based on data from Oracle Cerner Real-World Data (CRWD), a national repository from over 130 U.S. health systems covering > 100 million patients, from Jan. 2014 to Sep. 2022. Over 500,000 adults with a documented history of OUD and over 800,000 adults with a history of AUD were included in the analysis. Overall, the study reported a 40% lower rate of incident opioid overdose among individuals with OUD with a GIP/GLP-1 receptor agonist prescription compared to those without a prescription for these agents (adjusted incidence rate ratio [aIRR], 0.6; 95% confidence interval [CI], 0.43 to 0.83). Among individuals with AUD, those with a GIP/GLP-1 receptor agonist prescription had a 50% lower rate of incident alcohol intoxication compared to those without a prescription (aIRR, 0.5; 95% CI, 0.4 to 0.63). Findings were consistent across various subgroups, including those with type 2 diabetes mellitus (T2DM) and obesity.
Novo Nordisk announced topline results from the phase 3 SOUL (Semaglutide cardiOvascular oUtcomes triaL) (n=9,650) which evaluated oral semaglutide compared to placebo as adjunct to standard of care for the prevention of major adverse cardiovascular events (MACE) in patients with T2DM and established cardiovascular disease (CVD) and/or chronic kidney disease (CKD). The study demonstrated a 14% reduction in MACE (cardiovascular [CV] death, non-fatal myocardial infarction or non-fatal stroke) for people treated with oral semaglutide compared to placebo. Oral semaglutide (Rybelsus) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. It does not currently carry an indication for the reduction of MACE, but Novo Nordisk plans to submit for FDA approval for this indication in the near future.
Results from the 68-week STEP (Semaglutide Treatment Effect in People with obesity) 9 double-blind, randomized, placebo-controlled trial (n=407) have been published in the New England Journal of Medicine. Patients enrolled had obesity (body mass index [BMI] ≥ 30 kg/m2) and a clinical and radiologic diagnosis of moderate knee osteoarthritis (OA) with at least moderate pain. Randomization occurred in a 2:1 ratio to either once-weekly subcutaneous (SC) semaglutide (2.4 mg) or placebo. Patients also received counseling on physical activity and a reduced-calorie diet. The primary endpoint assessing the average change in body weight from baseline to week 68 was significantly improved with semaglutide compared to placebo (-13.7% versus -3.2%; p<0.001). Furthermore, the primary endpoint assessing the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (scale, 0 to 100, higher scores reflecting worse outcomes) from baseline to week 68 also demonstrated significant improvement with semaglutide compared to placebo (-41.7 points versus -27.5 points, p<0.001). Study findings demonstrated that SC weekly semaglutide resulted in significantly greater decreases in body weight as well as pain related to knee OA compared to placebo in patients with obesity and moderate to severe knee OA pain.
- The CDC has endorsed the Advisory Committee on Immunization Practices' (ACIP) recommendation for lowering the age for pneumococcal vaccination from 65 to 50 years of age. Individuals ≥ 50 years of age are instructed to discuss with an HCP to ensure they are up to date with pneumococcal vaccine recommendations.
The CDC has also endorsed ACIP’s recommendation for a second dose of the 2024 to 2025 COVID-19 vaccine six months after the first dose in (1) people ≥ 65 years of age, as well as in (2) individuals who are moderately or severely immunocompromised. The updated recommendations also allow for flexibility for additional doses (e.g., three or more) for moderately or severely immunocompromised individuals, in consultation with their HCP.
The agency has updated genomic surveillance for SARS-CoV-2 variants based on data collected in the U.S. from May 2023 to September 2024 with lineages predominantly including descendants of Omicron XBB and JN.1. Several XBB descendants circulated in summer and fall of 2023, and JN.1 (not an XBB descendant) was the predominant circulating variant by Jan. 2024; following this, descendants of JN.1 emerged. COVID-19 cases increased during both periods of either variant being predominant and when both variants were co-circulating.
The CDC has issued a Morbidity and Mortality Weekly Report (MMWR) describing laboratory-confirmed influenza-associated hospitalizations in the U.S. from 2010 to 2023 according to data from the Influenza Hospitalization Surveillance Network (FluSurv-NET). Although there was significant variation in influenza-associated hospitalizations across the seasons, adults ≥ 65 years of age consistently had the highest hospitalization rate across all age groups for each season, followed by children 0 to 4 years of age for most seasons. In those hospitalized with influenza, the prevalence of at least one underlying medical condition increased with increasing age: 36.9% among children 0 to 4 years of age and 95.4% among adults ≥ 65 years of age, with the most common underlying medical conditions being asthma, neurologic disorders, and obesity in children and hypertension, obesity, chronic metabolic disease, chronic lung disease, and CVD in adults.
The CDC published an MMWR on influenza and COVID-19 vaccination coverage among health care personnel in the U.S. during the 2023 to 2024 respiratory virus season. Data from the CDC’s National Healthcare Safety Network (NHSN) demonstrated influenza vaccination coverage was 80.7% for acute care hospital personnel and 45.4% among nursing home personnel whereas coverage with 2023 to 2024 COVID-19 vaccination was 15.3% among acute care hospital personnel and 10.5% among nursing home personnel.
Shortage Updates
All strengths of Novo Nordisk’s semaglutide (Ozempic) formulation for select patients with T2DM are available, along with all strengths of the semaglutide (Wegovy) product indicated for weight management. Novo Nordisk’s liraglutide (Saxenda) for weight management 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.
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 are also being reported; most 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.
Drug Information Highlights
AstraZeneca will be discontinuing twice daily exenatide (Byetta) and once weekly exenatide (Bydureon Bcise). The SC GLP-1 receptor agonist is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Bydureon Bcise is also indicated for this use in pediatric patients ≥ 10 years of age.
The FDA has approved a modification to the Opioid Analgesic REMS requiring that manufacturers participating in the Opioid REMS start providing pre-paid drug mail-back envelopes upon request to outpatient pharmacies and other dispensers of opioid analgesics by Mar. 31, 2025. The intent of the requirement is for patients and caregivers to receive a free, pre-paid drug mail-back envelope from dispensers of opioids that order the envelopes from the REMS. Additionally, a new patient education handout will be included with each envelope that reviews the risk of unused opioids and importance of proper disposal.
The agency has proposed removal of oral phenylephrine as an active ingredient that can be used in over-the-counter (OTC) monograph drug products for the temporary relief of nasal congestion; this proposal follows the FDA’s review of data that demonstrated oral phenylephrine is not efficacious for this use. The FDA will issue a final order following a public comment period (Nov. 8, 2024 to May 7, 2025) after which, if the agent is found to be ineffective and removed from the OTC monograph, drug products could not contain oral phenylephrine as a decongestant.
Rigel, the manufacturer of pralsetinib (Gavreto), has issued a safety communication to HCPs describing new findings on the increased risk of severe and fatal infection, including severe opportunistic infection. Corresponding updates will be made to the Warnings/Precautions section of the label for the kinase inhibitor to alert HCPs and patients. Prescribers are advised to monitor for signs and symptoms of infection and to treat based on local and institutional guidelines.
Drug Information Happenings
The American Heart Association (AHA)/American Stroke Association (ASA) has released an updated guideline on the primary prevention of stroke. This guideline replaces the 2014 version and includes recommendations that align with AHA’s Life’s Essential 8 for optimization of CV and cerebrovascular health.
A multisociety clinical practice guidance for the safe use of GLP-1 receptor agonists in the perioperative period has been published. Relatedly, the FDA also approved class-wide label updates to add a new Warning/Precaution for GLP-1 receptor agonists to address the serious risk of pulmonary aspiration for patients undergoing elective surgeries or procedures requiring general anesthesia or deep sedation.
The Institute for Clinical and Economic Review (ICER) released a final evidence report on comparative clinical effectiveness of tafamidis (Vyndamax/Vyndaqel), acoramidis (investigational), and vutrisiran (Amvuttra) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). The panel concluded that each agent demonstrated a net health benefit when compared to no disease-specific treatment; however, current evidence is not adequate to demonstrate a net health benefit for vutrisiran added to tafamidis when compared to tafamidis alone, and evidence is also inadequate to distinguish a net health benefit among the drugs when used as monotherapy.
All brand names are property of their respective owners.
CDC = Centers for Disease Control and Prevention
COVID-19 = coronavirus 2019
FDA = Food and Drug Administration
GIP = glucose-dependent insulinotropic polypeptide
GLP-1 = glucagon-like peptide-1
HCl = hydrochloride
HCP = health care professional
JAMA = Journal of the American Medical Association
REMS = Risk Evaluation and Mitigation Strategy
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2
Executive Editor: Anna Schreck Bird, PharmD
Deputy Editors: Erik Hamel, PharmD; Olivia Pane, PharmD, CDCES