Blog | 11/21/2023

Beyond the Blockbusters: The Obesity Opportunity

by Aashni Parikh, Sheela Hegde, and Alexis Froistad

Obesity impacts more than 1 billion people worldwide [1]. In 2022, over 5MM prescriptions for GLP-1s were written for weight management and the growing popularity of these drugs has shaken up the healthcare industry [2]. From celebrities to obesity clinics to biopharma companies, everyone wants a piece of the GLP-1 class. But with Novo and Lilly dominating the space, how can other biopharma companies really gain a piece?           

With first mover’s advantage and a portfolio of GLP-1s that have shown an increasing weight loss effect [figure 1], Novo’s Ozempic and Wegovy, and Lilly’s Mounjaro, have become synonymous with obesity drugs.

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Looking at the pipeline, however, many other companies are seeking to develop assets that not only improve tolerability and efficacy of weight loss, but also address associated comorbidities beyond type 2 diabetes.

  1. New assets in development have novel mechanisms of action that aim to improve weight-loss efficacy in ways that GLP-1s do not address. Figure 2 displays novel MOAs in the pipeline, with ~40 new assets in phase II and III clinical trials, including amylin receptor agonists, GIP receptor agonists, and peptide YY.
  2. New combinations of GLP-1s hope to address the current tolerability and safety issues associated with GLP-1s, namely gastrointestinal issues. In addition to nausea and constipation, studies have shown an increased risk of pancreatitis in obesity patients taking semaglutide (Wegovy/Ozempic) as compared to those taking a weight-loss medication that does not mimic GLP-1 [3]. Additional considerations include hypoglycemia in insulin-intensive patients, acute kidney injury, and macrovascular outcomes [4]. Figure 2 displays the pipeline of GLP-1 combination drugs that are in development, comprising ~50% of the ~40 assets in phase II and III trials.
  3. Moving beyond weight loss, obesity drugs are also in development for comorbid conditions. Type 2 diabetes and NASH dominate comorbidity development, while CKD, sleep apnea, and T1D are less crowded [figure 3]. These are subpopulations that companies can focus on to differentiate and carve out unique positions.
     

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Finally, there is much to learn from the evolution of treatments in other markets, such as hypertension and cholesterol management. From one drug in one class, the thiazide/thiazide-like diuretic chlorothiazide, the hypertension drug market evolved to include 60+ drugs across 6+ classes, including calcium channel blockers, ACE inhibitors, and ARBs [5][6]. Each drug and class have found a position in the market. In the anticholesterolemia market, despite the dominance of the statin class though the 1990s, there was still opportunity for later blockbusters. Ezetimibe (ACAT inhibitor) launched in 2002 with a safety profile [7] that addressed statin side effects such as myopathy, achieving $2B-$5B in annual sales before LOE.

Obesity drug development will likely follow, and the market is still early. With development activity focused on new MOAs, improved tolerability and safety, and comorbid specific subpopulations, more and more companies are entering the space and creating new generations of drugs that will shape a more complex and more personalized future clinical paradigm.
 

Sources

[1]  WHO: https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity

[2]  Fierce Healthcare Article: https://www.fiercehealthcare.com/health-tech/telehealth-companies-target-100b-weight-loss-drug-market-patients-grapple-access-costs#:~:text=in%20the%20U.S.-,In%202022%2C%20more%20than%205%20million%20prescriptions%20for%20Ozempic%2C%20Mounjaro,between%202021%20and%202022%20alone.

[3]  Nature Article: https://www.nature.com/articles/d41586-023-03183-3  

[4]  FDA Label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209637lbl.pdf

[5]  Saklayen 2016 Front Cardiovasc Med.: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763852/

[6]  Khalil 2023 NIH: https://www.ncbi.nlm.nih.gov/books/NBK554579/

[7]  Rosenson 2017 JACC: https://www.ncbi.nlm.nih.gov/books/NBK554579/

[8]  Biomedtracker and Datamonitor Healthcare Report: 2023 Post-ADA Report

[9]  Company Websites: Eli Lilly: https://www.lilly.com/, Novo Nordisk: https://www.novonordisk.com/, Pfizer: https://www.pfizer.com/, Boehringer Ingelheim: https://www.boehringer-ingelheim.com/, Zealand Pharma: https://www.zealandpharma.com/

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Author Bios

Aashni Parikh, Analyst and member of the Metabolic and Autoimmune Practice at Health Advances

Sheela Hegde, Partner and Managing Director, co-lead of the Metabolic and Autoimmune Practice at Health Advances

Alexis Froistad, Consultant and member of the Metabolic and Autoimmune Practice at Health Advances

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