Roche’s weight-loss drug trials yield positive results

Roche's substantial $2.7 billion acquisition of Carmot Therapeutics has begun to bear fruit, revealing encouraging early results in developing new weight-loss drugs. This strategic move aims to enhance Roche’s competitive edge in the weight-loss drug market, positioning it against industry giants like Eli Lilly and Pfizer. Notably, participants in a phase 1 trial who were administered Carmot’s oral GLP-1 candidate, CT-996, exhibited significant weight loss, indicating the drug's potential efficacy.

The findings from the phase 1 trial are promising — participants who took CT-996 for four weeks saw an average body weight reduction of 7.3%. This is a notable improvement compared to the 1.2% weight loss observed in the placebo group. The study's subjects were individuals with obesity but without type 2 diabetes. Roche regards the placebo-adjusted weight loss of 6.1% as clinically significant, suggesting that CT-996 could be a potent player in the weight-loss drug market.

Roche’s acquisition of Carmot Therapeutics provided a portfolio of GLP-1-based treatments, including once-weekly and once-daily injectables and an oral small molecule. Earlier this year, Roche released phase 1 data for its once-weekly injectable GLP-1/GIP agonist (CT-388), and now, the oral candidate CT-996 is showing promising potential.

While showing promising results, Roche's CT-996 must be compared with other competing drugs to gauge its market potential. Novo Nordisk's oral semaglutide, which requires administration on an empty stomach, achieved a 12.7% placebo-adjusted weight reduction in a phase 3 trial after 68 weeks. In contrast, Eli Lilly’s orforglipron, which has simpler dosing requirements, reached a 12.4% placebo-adjusted weight loss in a phase 2 trial after 36 weeks.

Importantly, participants in Lilly’s orforglipron study had not achieved a 5% weight loss after just four weeks, suggesting that CT-996 could offer a quicker onset of action. However, direct comparisons between trials are challenging due to differences in study design and baseline characteristics. Nonetheless, the data suggest that CT-996 could be competitive in the weight-loss market.

Ensuring safety and tolerability is crucial in drug development, and Roche has reported no significant safety concerns with CT-996. Adverse events were primarily mild or moderate gastrointestinal issues, consistent with other GLP-1 molecules, and there were no discontinuations due to the drug. Additionally, CT-996 levels in the blood appeared largely unaffected by food intake, indicating potential dosing flexibility.

Roche has outlined two primary applications for CT-996. First, it could be used to achieve glycemic control and drive weight loss. Second, it could serve as an oral maintenance therapy for weight loss after injectables. This is particularly relevant given studies showing that roughly 85% of people discontinue GLP-1 drugs within two years, often leading to weight regain. An effective oral maintenance therapy could meet this significant need.

Roche is continuing to explore CT-996 in the ongoing phase 1 trial. The next phase, set to begin in the fourth quarter of 2024, will involve two cohorts of 30 participants with obesity and type 2 diabetes. Roche also plans to initiate a phase 2 trial to investigate the drug’s efficacy and safety further.

Roche's strategic investment in Carmot Therapeutics highlights the growing importance of innovative weight-loss therapies in the pharmaceutical industry. As obesity remains a major public health challenge globally, the demand for effective and convenient weight-loss treatments is on the rise.

As the pharmaceutical industry continues to innovate in obesity treatments, the early success of CT-996 underscores the potential for oral GLP-1 therapies to meet the growing demand for effective weight-loss solutions. Roche’s efforts in advancing this treatment reflect its broader strategy to lead in metabolic health, offering hope to millions struggling with obesity.