Roche claims midstage win for obesity injectable

Roche has reported phase 2 results with a dual GIP/GLP-1 agonist obesity candidate, achieving weight loss of up to 22.5%, as it prepares for a phase 3 programme.

The phase 2 trial of CT-388, a once-weekly subcutaneous injection acquired as part of its $2.7 billion takeover of Carmot Therapeutics in 2023, showed "robust" weight loss and a "well-tolerated safety profile," said the company.

CT-388 achieved 22.5% placebo-adjusted weight loss at the highest dose tested (24 mg) at 48 weeks, with no signs of a plateau of efficacy, according to the just-released results of the 469-subject trial. Moreover, more than half (54%) of patients taking the drug reduced their BMI to below the threshold for obesity (30 kg/m2), versus 13% of the placebo group.

Almost all patients treated with the 24 mg dose (around 96%) lost 5% of their weight or more, with 87% hitting 10% or more, 48% losing at least 20%, and 26% crossing the 30% threshold. Meanwhile, gastrointestinal side effects – the main issue with GLP-1-directed medicines – were generally mild-to-moderate in intensity.

CT-388's mechanism of action and route of administration mean that CT-388's closest comparator is Eli Lilly's Zepbound (tirzepatide), which has been growing at a phenomenal rate thanks to data showing its dual GIP/GLP-1 activity improved on the weight loss achieved with Novo Nordisk's GLP-1 drug Wegovy (semaglutide). While it can be problematic trying to compare results from different trials, CT-388's weight-loss effect seems to be in roughly the same ballpark as Lilly's drug.

While weekly injectables Zepbound and Wegovy have been enjoying a duopoly in the obesity category to date, the market is likely to be shaken up by the recent launch of an oral formulation of Novo Nordisk's drug – which has shown strong uptake in its first few days on the market – as well as Lilly's oral GLP-1 orforglipron, which could be approved in the coming weeks.

Another disruptor could be Lilly's triple agonist retatrutide – targeting GLP-1, GIP, and glucagon – which recently showed average weight losses of up to 28.7% in its first phase 3 readout and was tipped as a drug to watch in 2026 by IQVIA, which has predicted sales could reach $10 billion from obesity alone in five years and twice that amount from use in diabetes. Meanwhile, dozens of other potential rivals from Novo Nordisk and others are coming through the industry's collective pipeline.

It remains to be seen how Roche's latecomer into the market will fare, assuming the phase 3 programme goes to plan, but the company is pressing ahead with a two-trial phase 3 programme for CT-388 that is due to commence later this quarter.

It has invested heavily in its obesity and diabetes pipeline, also licensing a long-acting amylin analogue (petrelintide) from Zealand Pharma last year for $1.4 billion upfront, and currently has six candidates in clinical testing.