Amgen's MariTide Obesity Drug Shows Promise, Faces Dosing Challenges in Phase 3 Trials

Amgen's obesity candidate MariTide demonstrated significant weight loss potential in a recent phase 2 study, but gastrointestinal side effects have prompted the company to adjust its dosing strategy for upcoming phase 3 trials. The GLP-1 agonist and GIPR antagonist, designed for monthly administration, aims to compete in the increasingly crowded obesity treatment market.

Phase 2 Results: Impressive Weight Loss, Concerning Side Effects

Results from part 1 of Amgen's phase 2 MariTide study, presented at the American Diabetes Association (ADA) 85 Scientific Sessions and published in the New England Journal of Medicine, showed promising efficacy. Patients with obesity lost an average of 16.2% of their baseline body weight, while those with both Type 2 diabetes and obesity shed 12.3% on average. For patients who completed the entire 52-week study period, these figures increased to 19.9% and 17%, respectively.

However, the trial also revealed significant gastrointestinal side effects, particularly in higher-dose, fixed-dose arms. Discontinuation rates due to gastrointestinal events ranged from 12% to 27% in non-dose-escalation groups, compared to up to 7.8% in dose-escalation cohorts. Nausea and vomiting were frequently reported, with vomiting rates as high as 92% in some treatment arms.

Revised Phase 3 Strategy: Slower Dosing Schedule

In response to these findings, Amgen has implemented a modified dosing plan for its phase 3 MARITIME program. The new approach involves a three-step dose escalation over eight weeks, starting at 21 mg before increasing to 35 mg and finally to 70 mg. This strategy aims to mitigate the gastrointestinal side effects while maintaining efficacy.

Dr. Jay Bradner, Amgen's R&D head, emphasized the potential benefits of MariTide's monthly or less frequent dosing, stating, "MariTide's monthly or less frequent dosing has the potential to improve adherence and long-term weight control, providing the opportunity to optimize health outcomes for people living with obesity, Type 2 diabetes and related conditions."

Market Implications and Analyst Perspectives

While Amgen's stock experienced a 5% decline following the ADA presentation, market analysts remain divided on MariTide's prospects. Jefferies analysts predict that phase 3 data will exceed expectations, positioning MariTide as a "player on the market" with solid efficacy and a competitive dosing profile.

Conversely, Citi Research analysts argue that the three-step dose escalation design, while potentially improving adverse event rates, "detracts from the convenience narrative" of a long-acting injectable.

Despite these concerns, Amgen maintains confidence in MariTide's commercial viability. Susan Sweeney, Amgen's head of obesity, described the dose-escalation process as "quite simple" and highlighted the benefits of a monthly maintenance therapy for busy primary care physicians.

As Amgen moves forward with its phase 3 trials, expected to conclude in 2027, the pharmaceutical industry will be closely watching to see if MariTide can overcome its dosing challenges and establish itself as a competitive force in the obesity treatment landscape.