Roche, Viking, and Syntis showcase obesity drug candidates
There has been a flurry of clinical readouts for new weight-loss therapies in the last few days, with Roche, Viking Therapeutics, and Syntis all showing off new drug candidates.
Roche hails competitive profile for enicepatide
Roche has revealed new phase 2 data with enicepatide (formerly CT-388), its potential rival to Eli Lilly's dual GIP/GLP-1 agonist behemoth tirzepatide, saying the drug offers "a potential best-in-disease profile" in adults living with type 2 diabetes (T2D) and obesity or who are overweight.
At the highest dose tested (24 mg), enicepatide – which was acquired by Roche as part of its $2.7 billion takeover of Carmot Therapeutics in 2023 – achieved a mean reduction of 2.65% in HbA1c, a marker for glucose control, along with an average weight loss of 15.5% at 48 weeks. The drug previously showed activity in another phase 2 study involving non-diabetic patients with overweight/obesity, achieving a 22.5% weight reduction at the same timepoint.
Like Lilly's blockbuster drug, which is sold as Mounjaro for diabetes and Zepbound for weight loss, enicepatide is administered by subcutaneous injection once a week. Roche thinks it has some key differences, however, including prolonged activity in the body that it hopes will deliver a step up in efficacy. It is testing the drug in two phase 3 weight-loss studies – ENITH-1 and ENITH-2 – and is planning a phase 3 programme in diabetes next year.
Viking rises on early clinical results for VK2735
Another dual GIP/GLP-1 agonist – Viking Therapeutics' VK2735 – achieved weight loss of 17.7% with a weekly dose (17.5 mg) at 21 weeks in a phase 1 trial. Moreover, the average reduction was maintained when the injection frequency dropped to every other week or monthly through week 33, pointing to the potential for less frequent dosing than tirzepatide.
For a group that remained on weekly injections, the weight loss increased to 22%, which the company said could increase with additional follow-up and, if so, looks competitive with Lilly's drug. Meanwhile, rates of gastrointestinal-related adverse events – a perennial issue with incretin drugs – were comparable to placebo during the 12-week maintenance dosing period.
Viking – which saw its shares climb by a third on the news – is also developing an oral formulation of VK2735. That had a phase 2 readout last year, but failed to generate much excitement as the data did not look any better than the current oral options, Novo's Wegovy (semaglutide) and Lilly's Foundayo (orforglipron). The company said it intends to explore oral maintenance dosing regimens in an extension to that trial.
Syntis takes a different tack with SYNT-101
Finally, Syntis Bio reported the results of an early-stage trial of SYNT-101, a non-incretin, oral therapy for weight loss that is thought to work by temporarily redirecting nutrient absorption in the small intestine – a strategy for weight loss that underlies gastric bypass surgery – by deploying a temporary polymer coating over the lining of the duodenum.
In the phase 1/1b trial, SYNT-101 was well tolerated, with placebo-like side effects, and generated increases in GLP-1 and PYY, both hormones associated with feelings of fullness. It also reduced levels of ghrelin, a hormone that signals hunger. The changes were comparable to those seen in people undergoing bypass surgery.
Syntis said it plans to start a phase 2 study of SYNT-101 next year, and hopes that its drug could serve as both a standalone therapy for weight loss or a combination with existing medicines.
