Survodutide, a novel glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) dual agonist developed by Boehringer Ingelheim, has shown promising Phase II results in patients with overweight or obesity and metabolic dysfunction-associated steatohepatitis (MASH). The data, presented at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD) 2024, highlight significant reductions in body weight and blood pressure, suggesting a potential new therapeutic avenue for these conditions.
Significant Weight Reduction in Obesity
The Phase II trial (NCT04667377) results, presented by Dr. Anton Pekcec at EASD, revealed that almost 40% of overweight or obese patients treated with survodutide achieved more than a 20% reduction in body weight after 46 weeks. Notably, the body weight reduction did not plateau by week 46, indicating that longer treatment durations could potentially yield further reductions. This suggests a sustained effect that warrants further investigation in Phase III studies.
Promising Results in MASH
In a separate Phase II trial (NCT04771273) focusing on MASH, survodutide demonstrated significant promise in reducing blood pressure. These findings are particularly relevant given the high prevalence of hypertension in patients with MASH, offering a potential dual benefit from a single therapeutic agent.
Safety and Tolerability Considerations
While survodutide showed significant efficacy, some patients discontinued treatment due to adverse events. These events were primarily attributed to the rapid dose-escalation phase of the trials. Dr. Pekcec suggested that a more gradual dose escalation strategy could mitigate these issues and improve the overall tolerability of the drug.
Addressing Concerns About Muscle Loss
During the question-and-answer session at EASD, concerns were raised regarding the potential catabolic effects of glucagon on amino acids and the risk of muscle loss. Dr. Pekcec clarified that while survodutide does decrease amino acid levels in the bloodstream, this reduction does not directly correlate with muscle loss. He further explained that glucagon primarily mediates energy expenditure, while GLP-1 agonists primarily influence eating behavior, suggesting a balanced mechanism of action.
Dual Mechanism of Action: A Novel Approach
The dual mechanism of action of survodutide, targeting both GCGR and GLP-1R, offers a unique approach to managing obesity and MASH. Key opinion leaders interviewed by GlobalData have expressed that a GCGR/GLP-1R dual agonist would be highly desirable if it could increase glucagon activity, reduce weight and glucose levels, lower blood pressure, improve lipid profiles, and sustain resting metabolic rate. The current data suggests that survodutide has the potential to meet these criteria.
Competitive Landscape
According to GlobalData’s Pharma Intelligence Center, the obesity pipeline includes 20 Phase III, 59 Phase II, and 96 Phase I candidates globally. In the MASH space, there are nine Phase III, 67 Phase II, and 83 Phase I candidates. Survodutide's promising Phase II results position it as a potential contender in these competitive landscapes, offering a novel dual-agonist approach that could address multiple aspects of these complex metabolic disorders.
