Roche’s $2.7B weight-loss wager delivers early oral GLP-1 win

Roche’s $2.7B weight-loss wager delivers early oral GLP-1 win

Roche’s $2.7 billion bet on Carmot Therapeutics has delivered another early win. Participants in a phase 1 trial lost 7.3% of their body weight after taking Carmot’s oral GLP-1 prospect for four weeks, suggesting the candidate can hold its own against rival molecules from the likes of Eli Lilly and Pfizer.

Buying Carmot gave Roche control of once-weekly and once-daily GLP-1 injectables, plus an oral small molecule. Roche reported phase 1 data on a once-weekly injectable GLP-1/GIP agonist in May and has now followed up with an early look at the efficacy of its oral sibling CT-996. Carmot showed the molecule is suitable for once-daily oral dosing in October but the Roche release is the first look at efficacy.

After four weeks, participants on CT-996 had lost 7.3% of their body weight, on average, compared to a 1.2% reduction in the placebo cohort. The subjects had obesity but not type 2 diabetes. Roche said the 6.1% placebo-adjusted weight reduction is clinically meaningful.

The figure also looks commercially meaningful. Novo Nordisk linked its oral semaglutide formulation to a 12.7% placebo-adjusted reduction in weight in a phase 3 trial. But that drop came after 68 weeks and the molecule needs to be taken on an empty stomach with a sip of water. Lilly’s orforglipron, which has simpler dosing requirements, achieved 12.4% placebo-adjusted weight loss after 36 weeks in phase 2.

While Roche reported less weight loss, CT-996 triggered the improvements after four weeks of dosing. Participants in Lilly’s orforglipron study were yet to lose 5% of their body weight after four weeks. Gaps in the data provided by Roche, such as weight at baseline, make the always tricky cross-trial comparisons particularly tough but the available evidence suggests CT-996 could be competitive.

Similarly, the limited safety and tolerability data provided by Roche are free from red flags. Subjects had mostly mild or moderate gastrointestinal-related adverse events, side effects associated with all GLP-1 molecules, and there were no discontinuations related to the drug. Levels of CT-996 in the blood were largely unaffected by whether the subject had eaten, suggesting dosing flexibility is possible.

The data led Roche to identify two use cases. As well as being used to achieve glycemic control and drive weight loss, patients could potentially use CT-996 for oral weight maintenance therapy after injectables. A recent study found (PDF) around 85% of people stop taking GLP-1 drugs within two years. Another study showed people regain weight after stopping treatment, creating a need for maintenance therapies.

Roche is continuing to test CT-996 in the phase 1 trial. The next part of the trial will enroll two sequential cohorts of 30 participants with obesity and type 2 diabetes. Roche plans to start that part of the study in the fourth quarter and also has its sights on a phase 2 study.

 

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