The race for an effective oral obesity pill is intensifying, with Novo Nordisk, Roche, and Terns Pharmaceuticals all presenting new data on their respective candidates at the recent European Association for the Study of Diabetes annual meeting. These results offer a glimpse into the potential of each drug, but also highlight the challenges of balancing efficacy and tolerability in obesity treatments.
Efficacy and Tolerability Trade-offs
After four weeks of dosing, Roche's CT-996 led the pack with a 6.1% placebo-adjusted weight loss. However, this efficacy came at the cost of tolerability, with high rates of nausea (83.3%), diarrhea (50.0%), and vomiting (33.3%) reported. Jefferies analysts suggested that Roche's rapid dose titration might explain both the strong efficacy and the adverse events. According to BMO analysts, Roche remains a relevant player in obesity development, even if they are a step behind leaders like Lilly and Novo.
Novo Nordisk's oral amycretin, which engages both GLP-1 and amylin pathways, demonstrated a 4% placebo-adjusted weight loss. Truist analysts noted that the tolerability update was "a bit underwhelming" but reflected the lack of positive differentiation rather than a downside versus other oral GLP-1 drugs. BMO analysts highlighted the importance of amylin, noting its potential benefits separate from and synergistic to the GLP-1 class in treating obesity.
Terns Pharmaceuticals' TERN-601 achieved a 4.9% placebo-adjusted weight loss. Jefferies analysts pointed out that Terns is taking a novel approach, with the drug accumulating in the gut in a manner that meaningfully extends its effective exposure, similar to a long-acting oral. This could allow for higher doses to maximize weight loss without causing intolerable side effects.
Manufacturing and Formulation Challenges
Beyond efficacy and tolerability, manufacturing challenges loom large, particularly for peptide-based drugs like Novo's amycretin. Jefferies analysts estimate that even conservative sales projections for amycretin could require over 30 tonnes of API per year if the oral route is prioritized, suggesting that reformulation for greater bioavailability is critical.
Terns faces its own set of challenges, including the need for patients to take multiple tablets and the potential for variability in drug exposure. Like its rivals, Terns needs to generate Phase II data to address these questions and further refine its approach.
Interpreting Early Data
While these early results offer valuable insights, analysts caution against drawing definitive conclusions based on cross-trial comparisons. Differences in trial designs and patient populations can confound attempts to directly compare efficacy. Larger Phase II trials will be crucial for clarifying the true competitive profile of each candidate and identifying the optimal balance between efficacy and tolerability.
