Roche Sees Early ROI on $2.7B Carmot Buy with Phase I Data for Obesity Candidate

Roche Tower_iStock, olli0815

Pictured: Roche tower in Basel, Switzerland/iStock, olli0815

Roche subsidiary Genentech on Thursday unveiled Phase Ib data for its investigational weight-loss treatment CT-388, demonstrating that a once-weekly subcutaneous shot could significantly lower body weight in healthy adults with obesity.

At 24 weeks of follow-up, CT-388 lowered body weight by 18.8% versus placebo. The effect was statistically significant, with a p-value less than 0.001, according to Genentech’s announcement. In addition, 100% of treated patients showed more than 5% weight loss at 24 weeks, while 45% of participants lost more than 20% of their body weight.

A subgroup analysis also showed that all pre-diabetic participants at the start of the study achieved normal blood glucose levels after 24 weeks of treatment, while those in the placebo group saw no meaningful change in glycemic status.

In terms of safety, CT-388 was well-tolerated in the Phase Ib study with most of its side effects classified as mild to moderate in severity. There were also no unexpected safety signals and CT-388’s adverse event profile was consistent with other medications in the incretin drug class.

Levi Garraway, CMO and head of global product development at Roche, in a statement called Thursday’s data “highly encouraging” for CT-388 and further “underscore its potential to become a best-in-class therapy with durable weight loss and glucose control.” The company will continue to develop the candidate as a treatment for obesity and type 2 diabetes.

Initially developed by Carmot Therapeutics, CT-388 is a dual agonist of the GLP-1 and GIP receptors that shows none or minimal recruitment of β-arrestin proteins, which would otherwise interfere with the receptors’ downstream signaling cascades and dampen the overall therapeutic effects of the obesity treatment, according to Carmot’s website.

CT-388’s biased mechanism of action allows it to prevent or lower desensitization to treatment, prolonging its pharmacological activity. CT-388 is designed to be delivered via a once-weekly subcutaneous injection.

Roche acquired Carmot for $2.7 billion in December 2023 and is now running a multi-part, multi-cohort Phase I trial of CT-388 in overweight or obese patients with or without obesity.

In addition to CT-388, the Carmot deal gave Roche other promising obesity candidates including the Phase II CT-868, which is also a dual agonist of the GLP-1 and GIP receptors but is designed as a daily subcutaneous injection. Roche also owns the early-stage CT-996, which is an oral small molecule GLP-1 agonist.

Thursday’s readout makes Roche a potential contender in the lucrative obesity market, which is currently dominated by Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide). Despite efforts from the frontrunners to boost their manufacturing capacities, they are both still unable to keep up with the market’s voracious appetite for weight-loss treatments, causing protracted drug shortages.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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