Roche's $2.7B Weight-Loss Bet Yields Early Oral GLP-1 Success

Roche's recent $2.7 billion acquisition of Carmot Therapeutics is already showing promising results. Early data from a phase 1 clinical trial indicated that participants who took Carmot’s oral GLP-1 candidate CT-996 experienced a 7.3% reduction in body weight over a four-week period. This suggests that CT-996 could compete effectively with similar drugs from major pharmaceutical companies like Eli Lilly and Pfizer.

The acquisition provided Roche with access to multiple GLP-1 formulations, including once-weekly and once-daily injectables, as well as an oral small molecule. Earlier this year, Roche presented phase 1 data on its once-weekly injectable GLP-1/GIP agonist. The latest results now offer the first insight into the efficacy of the oral version, CT-996, which was shown to be suitable for once-daily oral administration in earlier studies.

In the recent trial, participants who were administered CT-996 lost an average of 7.3% of their body weight, compared to a 1.2% reduction in the placebo group. These subjects were obese but did not have type 2 diabetes. Roche highlighted that the 6.1% placebo-adjusted weight loss is not only clinically significant but also has substantial commercial potential.

Comparatively, Novo Nordisk’s oral semaglutide resulted in a 12.7% placebo-adjusted weight reduction in a phase 3 trial, but this occurred over 68 weeks and required patients to take the drug on an empty stomach with minimal water. On the other hand, Eli Lilly’s orforglipron achieved a 12.4% placebo-adjusted weight loss after 36 weeks in phase 2, featuring simpler dosing requirements. Despite CT-996 inducing less weight loss, it accomplished this within just four weeks. Participants in the Lilly trial had yet to achieve a 5% weight reduction within the same period.

While direct comparisons between these trials are challenging due to data gaps such as baseline weight, the initial evidence suggests that CT-996 holds competitive potential. Additionally, the safety and tolerability data for CT-996 appear favorable. Most adverse events were mild or moderate gastrointestinal issues, which are commonly associated with GLP-1 drugs, and none led to discontinuation of the drug. Importantly, the absorption levels of CT-996 were largely unaffected by food intake, implying flexible dosing options.

Based on these promising results, Roche sees two primary applications for CT-996. Beyond glycemic control and weight loss, the drug could be used for oral weight maintenance therapy following initial treatment with injectables. Recent research indicates a significant drop-off in GLP-1 drug usage within two years, with 85% of patients discontinuing treatment. Another study showed that weight regain is common after stopping GLP-1 therapy, highlighting a clear need for maintenance treatments.

Roche plans to continue the phase 1 trial of CT-996 by enrolling two new cohorts of 30 participants each, focusing on individuals with obesity and type 2 diabetes. This next stage is slated to begin in the fourth quarter. Additionally, Roche is planning a phase 2 study to further investigate CT-996’s potential benefits.