Aleniglipron

Eli Lilly’s injectable obesity drug Zepbound has been proven more effective than Novo Nordisk’s Wegovy. But in the battle of the pills, it appears to be the other way around. Lilly on Thursday disclosed that its oral product orforglipron had disappointed in the first of two pivotal trials, with weight loss of around 11% after 72 weeks. This trails Novo’s oral version of Wegovy, which scored weight loss of 13% in a roughly comparable trial. But the pills, both of which are GLP-1 agonists, are not the only ones in development. Roche, Viking Therapeutics and Structure Therapeutics are some of the companies also working on oral obesity candidates, and some results, though early, look very promising. Lilly and Novo will have the battleground to themselves for some time. No other pills have started Phase 3 trials in obesity, and only a handful have mid-stage data. Structure’s aleniglipron is one, having achieved a decrease in weight of 6.2% at three months in a Phase 2a trial. Aleniglipron, formerly called GSBR-1290, is now in two Phase 2b obesity studies called ACCESS and ACCESS II, assessing lower and higher doses, respectively. Patients in both studies will receive the GLP-1 for around eight months, and topline weight loss data ought to come this year, CEO Ray Stevens recently told Endpoints News. He said he hoped that the ACCESS trials might yield weight loss of about 15%. Another company with three-month Phase 2a data is Shanghai-based Regor Therapeutics. According to a presentation at the American Diabetes Association’s meeting in June, RGT-075, as its product is known, produced weight loss of 5.4%, versus 0.5% with placebo. RGT-075 is currently being evaluated in a global Phase 2b study called COMO-1, in which the pill will be given to patients with obesity or overweight with weight-related comorbidities for around eight months. Topline data are expected at the end of 2025. Novo has another iron in the fire, though it’s not an incretin. Monlunabant is an inverse agonist of the CB1 receptor that was acquired via Novo’s purchase of Inversago Pharma for up to about $1 billion in 2023. In Phase 2, patients taking a 10 mg daily dose of monlunabant for four months managed weight loss of 7.1 kg, compared with 0.7 kg for those taking the placebo. At the higher doses of 20 mg and 50 mg, Novo said there was “limited additional weight loss.” Since the average baseline weight of patients in the trial was 110.1 kg, which translates to about 243 pounds, those given 10 mg of Novo’s drug lost around 6.4% of their weight. Monlunabant remains in Novo’s pipeline, but it is unclear whether any studies are ongoing. Another large pharma with an obesity pill is Roche. CT-996 was one of a suite of obesity assets that came to the Swiss giant from the $2.7 billion acquisition of Carmot Therapeutics in 2023. It helped Phase 1 subjects lose up to 7.3% of their weight within one month. At the time this was reported last September, this was the best weight loss seen with a pill at such an early timepoint. That record did not last long. The oral form of Viking Therapeutics’ VK2735 posted a weight loss figure of 8.2% at one month in its Phase 1 trial, which read out in November. Data from a Phase 2 trial are imminent and carry high expectations. Also closely-watched is yet another Novo asset, the GLP-1 and amylin agonist amycretin. This, too, exists in both shot and pill forms. The oral version yielded weight loss of 13.1% after four months in a Phase 1 trial, although this necessitated taking two pills a day. Oral amycretin remains at the Phase 1 stage in obesity, according to Novo’s pipeline. While these early-stage assets are promising, several of these companies will be unable to bring them to market without a larger partner. And oral drugs must be dosed higher than shots, making pills more expensive to manufacture. Even so, obesity pills are expected to be immensely lucrative, and this space will evolve at a furious pace in the months and years to come.