Roche’s incursion into the obesity space seems to be paying off so far based on the first clinical readout since the drugmaker scooped up Carmot Therapeutics for $2.7 billion.
The biotech caught the attention of the Swiss pharma based on its pipeline of three molecules that could potentially challenge market leaders Eli Lilly and Novo Nordisk in the booming obesity and diabetes space. Chief among those acquired assets was CT-388, an injectable dual GLP-1/GIP receptor agonist that was already in a phase 1b trial when Roche bought Carmot in December.
Now, Roche has released 24-week data from the study showing CT-388 produced average placebo-adjusted weight loss of 18.8%. All participants who received the therapy achieved weight loss of more than 5%, Roche noted, with 85% seeing weight loss of more than 10% and 45% achieving over 20% loss.
The results suggest that CT-388 can more than hold its own in an increasingly crowded field. While trial-to-trial comparisons should always be treated with caution, Novo Nordisk’s blockbuster Wegovy achieved 14.9% average weight reduction in STEP-1, a 68-week phase 3 trial of nondiabetic patients with obesity or who were overweight and had at least one weight-related comorbidity.
Another study called OASIS showed 15% weight loss after 68 weeks of treatment, with 34% seeing a 20% drop in their weight.
Meanwhile, Novo’s next-gen obesity bet CagriSema has shown 17.1% average weight loss in a 20-week phase 1 obesity trial, compared to 9.8% for Wegovy.
The readout appeared to be enough to enthuse investors, who sent Roche’s shares up 4% to 236.60 Swiss francs as of 11:25 a.m. local time.
Roche noted in this morning’s release that CT-388 was well tolerated with “mild to moderate gastrointestinal-related adverse events being the most common, consistent with the incretin class of medicines that CT-388 belongs to.”
When Roche drilled down into a subgroup of participants identified as “pre-diabetes,” the company noted that their blood sugar levels all reached normal levels after 24 weeks of receiving CT-388, while the levels of those who received placebo “remained largely unchanged.”
An additional cohort from the same trial will now evaluate obese patients with Type 2 diabetes over 12 weeks of treatment, with data set to read out in the second half of the year.
“We are very pleased to see the significant and clinically meaningful weight loss in people treated with CT-388,” Roche’s chief medical officer and head of global product development Levi Garraway, M.D., Ph.D., said in the release. “The results are highly encouraging for further development of CT-388 for both obesity and type 2 diabetes and underscore its potential to become a best-in-class therapy with durable weight loss and glucose control.”
Carmot’s attempt to differentiate its candidates from the competition rests on “biased signaling” that is designed to minimize recruitment of ß-arrestin. The approach is intended to achieve greater weight loss and glycemic control plus a more favorable tolerability profile.
Today’s results are focused on CT-388’s use as a monotherapy, but part of the attraction of the Carmot deal is the potential of allying the biotech's obesity assets with an anti-myostatin antibody that’s already in Roche’s pipeline.
The antibody, dubbed RO7204239, is being studied for its potential to strengthen the muscles of people with spinal muscular atrophy. The hope is that adding RO7204239 to the mix means that Roche has its own answer to the next holy grail of obesity medicine: weight loss without muscle loss.
“We know that incretins may have applicability into other disease areas,” Roche Pharmaceuticals CEO Teresa Graham told analysts on a call in February. “We would be looking at the assets that we acquired as part of the Carmot deal really as a backbone for future plays across cardiometabolism, but also potentially other disease areas as well.”