Clinical Highlights: December 2024 - Prime Therapeutics
Clinical Highlights: December 2024
Your monthly source for drug information highlights.
An analysis published in The Lancet details national- and state-level prevalence of overweight or obesity in individuals from 1990 to 2021. Additionally, the analysis forecasts overweight or obesity prevalence up to 2050. As of 2021, it was estimated that 15.1 million persons aged 5 to 14 years, 21.4 million persons 15 to 24 years, and 172 million adults ≥ 25 years of age had overweight or obesity. For adults ≥ 18 years of age, overweight was defined as having a body mass index (BMI) of 25 kg/m² to < 30 kg/m² and obesity was defined as a BMI of ≥ 30 kg/m². For individuals < 18 years of age, definitions were based on International Obesity Task Force criteria. Obesity prevalence has risen faster than overweight prevalence, particularly among adolescents. From 1990 to 2021, the percentage change in the age-standardized prevalence of obesity increased by 158% for male adolescents and 186% for female adolescents (15 to 24 years). Similarly, for adults, the percentage change in prevalence of obesity was 124% in men and 100% for women. Based on these trends, by 2050, another 3.3 million persons 5 to 14 years of age, 3.4 million persons 15 to 24 years of age, and 41.4 million adults aged ≥ 25 years will have overweight or obesity. This will result in the total number of children and adolescents with obesity/overweight being 43.1 million and the total number of adults estimated to be 213 million by 2050 with most states projected to have a third of adolescents (aged 15 to 24 years) and two-thirds of adults (≥ 25 years) with obesity.
The current White House administration has proposed expanded coverage by Medicare and Medicaid for drugs to treat obesity, including GLP-1 agents. Based on the proposal, under Medicare coverage out-of-pocket costs for these medications would be reduced by up to 95% for some enrollees, and about 4 million Medicaid enrollees would have access to these therapies. Furthermore, the Centers for Medicare and Medicaid Services (CMS) has proposed to reinterpret the statute to no longer exclude anti-obesity medications for treating obesity from being covered under Medicare Part D and to require Medicaid to cover these drugs when used for obesity. Comments on the proposed rule for calendar year 2026 Medicare Advantage and Part D plans are being accepted until Jan. 27, 2025.
An analysis published in Proceedings of the National Academy of Sciences provides an estimation that 42,027 deaths annually in the United States (U.S.) could be avoided with expanded access to GLP-1/GIP medications for weight loss with 11,769 of these being individuals with overweight or obesity and type 2 diabetes mellitus (T2DM). The expanded access assessment is based on providing medication to everyone who is eligible, with uptake rate requiring eligible individuals to receive health care and to be willing to take these medications. Authors noted the estimates are dependent on current data related to effectiveness and utilization of the medications as well as expanded access when neither cost nor supply are barriers to use. The analysis did not include the potential impact of certain health conditions, preventive interventions or lifestyle adjustments on obesity-related mortality.
- Detailed results from the three-year safety analysis of the randomized, double-blind, phase 3 SURMOUNT-1 study (n= 2,539) enrolling patients with obesity and prediabetes (n=1,032) have been published in the New England Journal of Medicine (NEJM). Significantly fewer patients were diagnosed with T2DM in the weekly tirzepatide arm than in the placebo arm (1.3% versus 13.3%; hazard ratio [HR], 0.07; p<0.001). Furthermore, after 17 weeks off study drug, significantly less patients in the tirzepatide arm had T2DM (2.4% versus 13.7%; HR, 0.12; p<0.001). The average percent change in body weight was significantly improved with all tirzepatide doses (5 mg dose: -12.3%; 10 mg dose: -18.7%; 15 mg dose: -19.7% versus -1.3% with placebo; p<0.001 for all doses versus placebo).
Study findings from the randomized, double-blind, phase 3 SUMMIT trial (n=731) evaluating tirzepatide for adults with heart failure with preserved ejection fraction (HFpEF) and obesity have been published in the NEJM. After a median follow-up duration of 104 weeks, the composite endpoint of adjudicated death from cardiovascular causes or a worsening heart failure (HF) event was significantly improved in patients who received tirzepatide compared to placebo (9.9% tirzepatide versus 15.3% placebo; HR, 0.62; p=0.026). This was primarily driven by the worsening HF event component of the endpoint being significantly improved in patients with tirzepatide (8% tirzepatide versus 14.2% placebo; HR, 0.54; 95% confidence interval [CI], 0.34 to 0.85). The component of the primary endpoint evaluating adjudicated death from cardiovascular causes was not statistically different (2.2% versus 1.4%, respectively; HR, 1.58; 95% CI, 0.52 to 4.83).
Topline results have been reported by Eli Lilly from the open-label, randomized, 72-week, phase 3b SURMOUNT-5 clinical trial. This study compared tirzepatide (Zepbound) and semaglutide (Wegovy) for weight loss in 751 adults with obesity or overweight with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) and without diabetes. In the trial, Zepbound resulted in a 47% greater relative weight loss compared to Wegovy. Weight loss on average was greater with Zepbound (20.2%) compared to Wegovy (13.7%). Additionally, 31.6% of patients receiving Zepbound reached ≥ 25% body weight loss, whereas only 16.1% of Wegovy patients achieved this endpoint.
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The CDC is reporting influenza-like illness (ILI) for the week ending Dec. 21, 2024 (week 51). Seasonal influenza activity continues to increase with 17 jurisdictions reporting high activity and nine reporting very high activity; the remainder of jurisdictions are reporting moderate, low or minimal activity. Influenza A(H1N1)pdm09 and A(H3N2) viruses continue to co-circulate this week. As of Dec. 9, 2024, the FDA is reporting available product from all manufacturers of antiviral influenza medications.
The CDC published a Morbidity and Mortality Weekly Report (MMWR) with recommendations from the Advisory Committee on Immunization Practices’ (ACIP) Oct. 2024 meeting. ACIP previously recommended a 2024–2025 COVID-19 vaccination for all individuals at least six months of age, and in Oct. 2024 recommended a second dose of the 2024–2025 COVID-19 vaccine, six months after the prior dose, for adults ≥ 65 years of age and for persons at least six months to 64 years of age with moderate to severe immunocompromise. Based on shared decision making, individuals at least six months of age with moderate or severe immunocompromise may receive additional doses (e.g., a total of ≥ 3 doses).
A randomized, placebo-controlled clinical trial (n=335) evaluated simultaneous versus sequential (one to two weeks apart) administration of an mRNA COVID-19 vaccine and inactivated influenza vaccine in nonpregnant patients ≥ 5 years of age and found that the percentage of individuals with at least one moderate or severe reaction (fever, chills, myalgia, and/or arthralgia) within 7 days after vaccination was comparable. Study results support simultaneous administration as an option for these vaccines.
The CDC released a publication describing methods to reduce risk for respiratory viruses (e.g., COVID-19, influenza, respiratory syncytial virus [RSV]) during the holiday season. An increase in RSV activity is being reported in the southern and eastern U.S. The CDC anticipates influenza and COVID-19 hospitalization to increase in the near future.
An MMWR describing COVID-19, influenza and RSV vaccination coverage in U.S. adults in fall 2024 reported that, as of Nov. 9, 2024, an estimated 35% and 18% of adults have received influenza and COVID-19 vaccines, respectively, for the upcoming respiratory virus season. For RSV vaccination in eligible populations, 40% of adults who are ≥ 75 years of age and 32% of adults 60 to 74 years of age who are at an increased risk for severe RSV disease have ever received a vaccine.
The CDC released an MMWR which reported on coverage with COVID-19, influenza and RSV vaccines among nursing home residents in the U.S. As of Nov. 10, 2024, 30% of nursing home residents had received a 2024–2025 COVID-19 vaccine, and in nursing home facilities that reported vaccination, 58% of residents had received influenza vaccination while only 18% had received RSV vaccination.
Shortage Updates
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
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The FDA has issued a Drug Safety Communication to warn of serious liver injury in patients without cirrhosis being treated with obeticholic acid (Ocaliva) for primary biliary cholangitis (PBC), with some cases requiring liver transplant. A contraindication for use in patients with advanced cirrhosis was added to Ocaliva’s labeling in 2021 due to the potential for serious harm in these patients. For patients without cirrhosis who are taking Ocaliva, frequent liver test monitoring is essential to identify declining hepatic function as Ocaliva should be discontinued if there is any evidence of liver disease progression or if efficacy is not established.
- The FDA has issued a communication regarding the agency's investigation into serious risks of hematologic malignancy following receipt of elivaldogene autotemcel (Skysona), an autologous hematopoietic stem cell (HSC)-based gene therapy. Additional reports of these malignancies, including life-threatening events, have occurred since the September 2022 approval of the product. Skysona received Accelerated Approval to slow the progression of neurologic dysfunction in boys 4 to 17 years of age with early, active cerebral adrenoleukodystrophy (CALD) and carries a Boxed Warning for hematologic malignancy. The FDA is assessing the need for additional regulatory action based on the serious risks of hematologic malignancies (e.g., hospitalization, allogeneic hematopoietic stem cell transplantation [HSCT], death). Health care providers (HCPs) are advised to carefully consider alternative treatments, including allogeneic HSCT for patients with a suitable, willing, and available human leukocyte antigen (HLA)-matched donor, before treating a child with Skysona.
- Endo has expanded its previously announced July 2024 voluntary recall of clonazepam orally disintegrating tablets (schedule IV controlled substance) due to potential product carton strength mislabeling. The manufacturer’s ongoing investigation has found that certain clonazepam product lot numbers could contain cartons printed with the incorrect strength and National Drug Code (NDC) due to an error by a third-party packager. However, for each lot, the blister strips and tablets inside the product pack carry the correct strength.
- Magstim’s Horizon 3.0 Inspire has been cleared by the FDA for the treatment of major depressive disorder (MDD) in adults who have failed to achieve satisfactory improvement from prior antidepressant medication, and as an adjunct for the treatment of adults suffering from Obsessive-Compulsive Disorder (OCD). The transcranial magnetic stimulation (TMS) system is being promoted by the manufacturer as user-friendly for both experienced TMS providers as well as those who are new to TMS.
Drug Information Happenings
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The American Diabetes Association (ADA) has released the 2025 Standards of Care in Diabetes. In addition to new recommendations on nutrition and technology, additional guidance was added regarding the role of GLP-1 agents for cardiac and renal health benefits as well as continuing weight management therapy once weight loss goals have been achieved.
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The ADA has released a guidance statement recommending against use of non-FDA-approved compounded GLP-1 and dual GIP/GLP-1 products due to concerns regarding their content, safety, quality, and effectiveness. Medications from these drug classes are recommended in the ADA Standards of Care in Diabetes for individuals with T2DM.
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The CDC published an MMWR with updated recommendations for the dosing interval and schedule of Meningococcal Group B Vaccine (Bexsero) from the Oct. 2024 ACIP meeting; the updates align with the product labeling and harmonize with recommendations for Meningococcal Group B Vaccine (Trumenba). ACIP recommends Bexsero as a two-dose series with doses administered at intervals of zero and six months for healthy adolescents and young adults 16 to 23 years of age, based on shared clinical decision-making, and as a three-dose series with doses administered at zero, one to two, and six months for persons ≥ 10 years of age at increased risk.
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The U.S. Preventive Services Task Force released its 14th Annual Report to Congress which highlights high-priority evidence gaps related to clinical preventive services, including screening tests, counseling on healthy behaviors, and preventive medications. Future research areas are related to promoting health of people across the lifespan in all communities and improving health equity in underserved populations and high-risk groups.
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
mRNA = messenger ribonucleic acid
Executive Editor: Anna Schreck Bird, PharmD
Deputy Editors: Erik Hamel, PharmD; Olivia Pane, PharmD, CDCES