Roche trumpets potential ‘best-in-class’ obesity drug

Roche has reported early clinical data with its candidate obesity therapy CT-388, bought as part of its $3.1 billion takeover of Carmot Therapeutics that was announced last year.

A phase 1b trial of the dual GLP-1/GIP receptor agonist given as a weekly subcutaneous injection achieved an average weight loss of 18.8% after just 24 weeks, with all patients on the drug losing at least 5% of their body weight.

Moreover, 70% lost 15% or more, and nearly half (45%) lost at least 20%. Treatment with the drug also normalised blood glucose in all patients in a subgroup with pre-diabetes, and it was well-tolerated, with some mild to moderate gastrointestinal side effects that are in keeping with other drugs in the incretin class.

The drug is in the same class as Eli Lilly’s tirzepatide-based Mounjaro and Zepbound products, respectively for type 2 diabetes and obesity, and shares the GLP-1 agonist mechanism of Novo Nordisk’s semaglutide-based diabetes therapy Ozempic and Wegovy for obesity.

Roche's chief medical officer, Levi Garraway, said it is a “significant and clinically meaningful” result that sets up CT-388 as a potential “best-in-class therapy with durable weight loss and glucose control.”

Roche will need a stellar clinical profile for CT-388 if it is to have a chance of catching up with the market leaders, currently seeing blockbuster sales for their drugs as demand outstrips availability, and to differentiate the drug from dozens of other incretin therapies coming through the industry pipeline.

Analysts at JP Morgan recently doubled their predictions for the class to $71 billion within the next 10 years, with Novo Nordisk and Lilly sharing the bulk of the market.

According to the drugmaker, CT-388 has potent activity on both GLP-1 and GIP receptors, but has almost zero effect on beta-arrestin recruitment, a feedback process that results in the receptor being absorbed into the cell. That means the receptors are more likely to stay on the surface of cells, preventing them from becoming desensitised to the drug.

CT-388 is the lead asset from the Carmot acquisition and is also being studied in a phase 1 trial in people who are overweight or have obesity and type 2 diabetes. Phase 2 trials in obesity with and without diabetes are planned.

Carmot’s other candidates include CT-868, a dual GLP-1/GIP agonist already in phase 2 testing as a once-daily injection to treat type 1 diabetes patients who are overweight or have obesity, and CT-996, a once-daily oral, small molecule GLP-1 receptor agonist currently in phase 1.

Roche has said it also has plans to combine the drugs with some of its pipeline candidates, including drugs aimed at preserving muscle mass like anti-myostatin antibody GYM329.