The next wave of weight loss drugs at Eli Lilly and Novo Nordisk
Last Thursday, Eli Lilly and Novo Nordisk's stocks plunged amid increasingly intense competition among obesity drug developers. What’s in the pipelines at these pharmaceutical giants?
Ozempic, originally developed by Novo Nordisk for type 2 diabetes, has skyrocketed to fame as a weight loss solution, making it into the top 10 best-selling drugs of 2023 with $9 billion in revenue. Although not officially marketed for weight loss, Ozempic’s efficacy in this area led to the development and approval of Wegovy in 2021, specifically for obesity treatment. This success spurred other pharmaceutical companies to join the race to develop the best weight loss drug.
Eli Lilly’s contenders, Zepbound and Mounjaro (both tirzepatides), have shown exceptional promise. Mounjaro, in particular, demonstrated unprecedented weight loss in the SURMOUNT-1 clinical trials, with participants losing up to 22.5% of their body weight. This surpasses most other weight loss medications, including Wegovy, where individuals in Novo Nordisk’s STEP trial lost an average of about 15-18% of their body weight over 68 weeks. However, both medications are facing significant supply issues due to overwhelming demand.
Besides supply shortages, the weight loss drug market’s increasing competition likely contributed to Eli Lilly’s and Novo Nordisk’s recent stock declines.
Novo Nordisk, Lilly’s key competitor, markets several GLP-1 receptor agonists including Saxenda, Ozempic, Victoza, Xultophy, and Rybelsus for type 2 diabetes, and Wegovy for weight loss. Other players are also entering the fray: Amgen’s AMG 133 is in Phase 1 trials, while Pfizer is developing Somatrogon and PF-07081532 for diabetes and weight management. AstraZeneca’s already markets Bydureon and Byetta, with Cotadutide, a GLP-1/glucagon receptor dual agonist, in Phase 2 trials for weight loss. Altimmune’s Pemvidutide and Intarcia Therapeutics’ ITCA 650, an implantable device delivering exenatide, are also in clinical trials. Roche’s experimental oral GLP-1 tablet, CT-996, which recently completed Phase 1 trials, reported a 6.1% weight loss within four weeks and may directly compete with Eli Lilly’s new drug orforglipron currently in Phase 3.
Eli Lilly’s extensive obesity drug pipeline
Eli Lilly’s stock is rebounding, likely due to its extensive pipeline of promising weight loss drugs.
Orforglipron is a GLP-1 agonist taken once daily as an oral tablet, offering a welcome alternative to the injection-based weight loss drugs currently dominating the market. Phase 2 results, published last summer in the New England Journal of Medicine, reported a 14.7% mean weight reduction at 36 weeks (1).
Retatrutide is a triagonist (GIP/GLP-1/Glucagon receptor agonist) that achieved a 17.5% mean weight reduction at 24 weeks. In a secondary endpoint, retatrutide showed a remarkable mean weight reduction up to 24.2% at 48 weeks. Both orforglipron and retatrutide are currently in Phase 3.
Bimagrumab, Eloralintide, and Mazdutide are in Phase 2 trials for obesity treatment. In July 2023, Lilly acquired Versanis Bio, likely for its monoclonal antibody drug that promotes muscle growth called bimagrumab. This could address the issue of muscle mass loss seen in patients using GLP-1 agonists. Combining bimagrumab with semaglutides and other GLP-1 receptor agonists may help prevent it and thus promote the loss of primarily adipose (fat) tissues.
Eloralintide is a selective amylin receptor agonist that promotes fullness, potentially enhancing weight loss efforts. Mazdutide is a GLP-1 receptor/glucagon receptor dual agonist that showed promising results in terms of in weight reduction, waist circumference, blood lipids, blood pressure, and liver fat content in the GLORY-1 trial.
With these advancements, Eli Lilly is positioning itself as a leader in the obesity drug market, offering many innovative solutions for weight management.
Novo Nordisk is keeping up
Novo Nordisk currently has 7 weight management drugs and 10 diabetes drugs in Phases 1-3, showing a robust pipeline to rival Eli Lilly.
Phase 3 trials include Oral Sema, a long-acting GLP-1 agonist intended for once-daily treatment, positioning it as another strong competitor to Lilly’s orforglipron. Additionally, a higher dose of semaglutide, Semaglutide 7.2 mg, and the once-weekly injectable combination of amylin agonist cagrilintide and semaglutide known as CagriSema, are in Phase 3 trials. Phase 2 trials for CagriSema completed in mid-2022 demonstrated a 15.6% body weight reduction over 32 weeks (3), along with A1C reduction, making it a likely contender against Eli Lilly’s Zepbound once it receives regulatory approval.
Subcutaneous (injectable) and oral amycretin, currently in Phase 1, are potential competitors to Lilly’s Eloralintide as they are GLP-1 and amylin receptor agonists. Novo Nordisk’s acquisition of the Canadian pharmaceutical company Inversago has added INV-347 to its Phase 1 lineup. This next-generation oral tablet is a CB1 cannabinoid receptor blocker known to modulate appetite. Another CB1 receptor blocker, Monlunabant, is in Phase 2 trials.
With these advancements, Novo Nordisk is well-positioned to be a strong competitor in the obesity drug market.
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DISCLOSURE: I have no business relationships with any company mentioned in this article.