Roche's oral GLP-1 agonist shows promising weight loss in Phase 1

Genentech, part of the Roche Group, recently reported promising phase 1 results for its investigational oral GLP-1 receptor agonist, CT-996. The drug demonstrated a 6% weight reduction over four weeks compared to a placebo. This development follows Roche's $2.7 billion acquisition of Carmot Therapeutics, which included CT-996 and two injectable GLP-1/GIP receptor agonists. These therapies aim to address obesity, either alone or combined with type 1 or type 2 diabetes management.

Among the three therapies acquired through Carmot, the daily injectable GLP-1/GIP receptor agonist is in phase 2, while the other two are in phase 1 trials. Notably, the weekly GLP-1/GIP receptor agonist, CT-388, showed positive phase 1 results earlier this year in May.

The phase 1 trial of CT-996 is divided into three sections. Two parts, which involved 65 participants with obesity but not diabetes, have been completed. Results from these sections revealed a 7.3% weight reduction in the treatment group, compared to 1.2% in the placebo group. The third segment of the trial is slated to start later this year, also involving participants with obesity but no diabetes.

Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, remarked on the significance of these findings. He highlighted the potential of CT-996 to aid in chronic weight management and glycemic control. Garraway also noted that this is the second positive outcome from their burgeoning metabolic pipeline, which includes both oral and injectable treatments for various related diseases.

Compared to Novo Nordisk’s oral GLP-1 semaglutide, which achieved a 12.7% weight reduction over 68 weeks in its phase 3 trial, Roche's CT-996 shows considerable promise in a much shorter timeframe. Additionally, the safety and tolerability of CT-996 were consistent with other GLP-1 receptor agonists, with no unexpected side effects reported.

The weight loss drug market has significantly expanded since Novo Nordisk’s Wegovy (semaglutide) received approval for weight loss in 2021. This was followed by Eli Lilly’s GLP-1/GIP agonist, Zepbound (tirzepatide), in 2022. Both companies have seen substantial financial gains from these products, prompting other biotech and pharmaceutical companies to develop new weight loss drugs, some incorporating a GLP-1 component. For instance, Pfizer is currently in phase 2 trials for its oral GLP-1 receptor agonist, danuglipron.

Roche’s acquisition of Carmot has allowed it to enter the competitive weight-loss drug market. However, it remains uncertain whether Roche can match the successes of Novo Nordisk and Eli Lilly. Given that the Roche/Carmot therapies are still in early stages, they will need to demonstrate significant advantages in weight loss, safety, and convenience to gain approval and achieve profitability in the future.