GLP-1 Pipeline Update: November 2024 - Prime Therapeutics
GLP-1 Pipeline Update: November 2024
Quarterly view of the GLP-1 pipeline and anticipated indications
Editorial team
Maryam Tabatabai, PharmD
Editor-In-Chief
Vice President, Clinical Information
Carole Kerzic, RPh
Executive Editor
Clinical Pharmacist, Drug Information
Nicole Kjesbo, PharmD, BCPS
Executive Editor
Clinical Program Director, Pipeline
Lisa Schweizer, PharmD, JD
Director, Clinical Program Management
Deputy Editor
DISCLAIMER
The drug pipeline is fluid; the dates and information within this publication are subject to change. Nothing herein is or shall be construed as a promise or representation regarding past or future events and Prime Therapeutics expressly disclaims any and all liability relating to the use of or reliance on the information contained in this presentation. The information contained in this publication is intended for educational purposes only and should not be considered clinical, financial, or legal advice. By receipt of this publication, each recipient agrees that the information contained herein will be kept confidential and that the information will not be photocopied, reproduced, distributed to, or disclosed to others at any time without the prior written consent of Prime Therapeutics.
All brand names are property of their respective owners.
Introduction
The first glucagon-like peptide-1 receptor agonist (GLP-1) for type 2 diabetes mellitus was approved in 2005 and for chronic weight management in 2014. A decade later, a host of new GLP-1s and new indications for existing GLP-1s are being studied, including sleep apnea and diabetic nephropathy. Earlier this year, semaglutide (Wegovy) became the first weight loss drug to also be approved for the reduction of risk of serious cardiovascular events in patients with cardiovascular disease and obesity and overweight. Given the considerable continued growth expected in the GLP-1 pipeline, plus a new indication and a generic expected as early as December 2024, Prime Therapeutics’ talented team of clinical experts has developed this publication to focus on the GLP-1 emerging landscape. The risk to benefit profile of these agents and outcomes data are key as we evaluate the evidence. Moreover, holistic care of patients remains a cornerstone of care.
Prime Therapeutics’ GLP-1 Pipeline Update provides a credible clinical snapshot of what’s on the horizon, reporting the earliest estimated approval time period based on available data. Keep reading to learn more and visit the October Quarterly Drug Pipeline for more clinical insights on anticipated drugs in development.
Access the complete GLP-1 Pipeline Update table for November 2024.
GLP-1s by year and indication
GLP-1s by indication and year
GLP-1 pipeline FAQs
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Obstructive sleep apnea: tirzepatide (Zepbound) is awaiting an FDA decision for the treatment of moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity, with and without positive airway pressure (PAP) therapy. The placebo-controlled SURMOUNT-OSA trial evaluated Zepbound for the treatment of moderate to severe OSA in adults with obesity, without type 2 diabetes mellitus (T2DM). At week 52, Zepbound resulted in a significant reduction in the apnea-hypopnea index in individuals who were and were not receiving PAP therapy. The FDA could decide on Zepbound in December 2024.
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Diabetic nephropathy: An FDA decision for semaglutide (Ozempic) for the prevention of diabetic nephropathy in adults with T2DM and cardiovascular disease (CVD) is expected in January 2025. The phase 3 FLOW trial evaluated Ozempic in patients with T2DM and chronic kidney disease (CKD). The study reported that Ozempic resulted in a significant reduction in the risk of kidney disease-related events.
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The GLP-1s are being studied for a host of conditions. There are several phase 3 trials evaluating GLP-1s for indications, such as metabolic dysfunction-associated steatohepatitis (MASH), prediabetes, Alzheimer's disease, diabetic retinopathy, and osteoarthritis of the knee (in patients with obesity).
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Research in earlier phases or small trials include evaluation of GLP-1s for indications such as cystic fibrosis-related diabetes, polycystic ovarian syndrome (PCOS), chronic obstructive pulmonary disease (COPD), Prader-Willi syndrome (PWS), asthma, substance or alcohol use disorder, and as add-on to insulin for type 1 diabetes. Many of these trials are very small; therefore, it is too early to predict if GLP-1s will provide benefit for patients with these conditions.
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GLP-1 receptors are expressed in several tissues in the body, including the gastrointestinal tract, heart, lung, kidney, and brain. GLP-1s cause weight loss which has inherent health benefits, but the exact mechanism of GLP-1s for other indications is not fully known. Evidence suggests that GLP-1 signaling may mediate inflammatory pathways involved in some metabolic, pulmonary and neurologic disorders. For example, in the lungs, GLP-1s may reduce the inflammatory response, improve oxidative stress, regulate protease/anti-protease imbalance, improve airway mucus homeostasis, and reduce airway remodeling to provide benefit in patients with COPD. In the central nervous system, GLP-1s may impact neuronal function in conditions, such as Alzheimer's disease and Parkinson's disease, through multiple mechanisms. Data indicates that GLP-1s may reduce inflammation and tau phosphorylation and improve synaptic function. In addition, GLP-1s can impact substance or alcohol use disorder and Prader-Willi syndrome through their effect on satiety hormones.
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Typically, GI side effects of GLP-1s, such as nausea and vomiting, are dose-dependent, mild-to-moderate in severity, and occur mostly during initiation of therapy and up-titration. Gastrointestinal side effects of GLP-1s can be mitigated with appropriate dose escalation when initiating therapy. Patients prescribed a GLP-1 agent should also be encouraged to eat slowly, eat smaller meals, and if needed, adjust the timing of their GLP-1 dose in relation to food intake.
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There are no medications available in the U.S. indicated specifically to treat GI side effects from GLP-1s. Neurogastrx is studying the peripherally acting dopamine D2/D3 receptor antagonist investigational drug, metopimazine, for reducing the incidence, duration and severity of nausea and vomiting in individuals who received a single SC dose of semaglutide. Top-line results of the phase 2 trial demonstrated metopimazine led to a 40% reduction in the incidence of nausea and a 56% reduction in frequency of vomiting.
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On Dec. 21, 2024, several generic versions of liraglutide (Victoza) for the treatment of T2DM may become commercially available in the U.S. An authorized generic (AG) version launched in the U.S. in June 2024.
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Generics for exenatide (Bydureon), liraglutide (Saxenda) and dulaglutide (Trulicity) could be available in 2027. Generics for other agents are expected sometime after 2027.
Glossary
CVD Cardiovascular disease
FDA Food and Drug Administration
GLP-1 Glucagon-like peptide-1
GLP-1s Glucagon-like peptide-1 receptor agonists
HF Heart failure
MASH Metabolic dysfunction-associated steatohepatitis
OA Osteoarthritis
OSA Obstructive sleep apnea
PAD Peripheral arterial disease
SC Subcutaneous
T2DM Type 2 diabetes mellitus
U.S. United States