Danuglipron

In a move likely to intensify competition in the burgeoning Chinese market for weight loss drugs, Eli Lilly announced via social media Friday that regulators there have signed off on its popular dual GIP/GLP-1 receptor agonist tirzepatide. The approval comes less than a month after Novo Nordisk's Wegovy (semaglutide) gained a similar authorisation in the critical Asian market.Tirzepatide, which is sold as Mounjaro for diabetes and Zepbound for weight loss in other markets, represents Lilly's entry into China's potentially lucrative obesity treatment landscape. Chinese regulators cleared the drug for diabetes in late May.The rapid approvals of weight loss medicines underscores the Chinese regulator's recognition of rising obesity rates in the country. The latest national survey conducted during 2015-2019 by China's National Health Commission found that 34.3% of China's adult population is overweight, with 16.4% reported as obese.Upping capacity…The approval of Zepbound in China also comes at a time when Lilly is working to ramp up its production capabilities globally. The company recently invested $5.3 billion to expand an Indiana production site in a bid to alleviate shortages for both Mounjaro and Zepbound. That was on top of a previous $3.7-billion commitment.Novo has been working to solve supply challenges for its GLP-1 drugs as well, including via plans to build a $4.1-billion fill-finish facility in the US. The company said it would also expand a manufacturing site in Tianjin, China, which is expected to be operational in 2027.…as competition intensifiesA retrospective observational study published in JAMA Internal Medicine recently gave Lilly's drug a weight-loss edge over Wegovy, potentially foreshadowing results from an ongoing head-to-head trial between the two GLP-1 heavyweights.Meanwhile, competition in the obesity drug market is not limited to Lilly and Novo. Just this week, Pfizer announced it would continue developing a once-daily formulation of its oral GLP-1 agonist danuglipron, saying it was optimistic about being able to advance a "competitive oral GLP-1 molecule into registration enabling studies," while Roche has also reported promising early-stage data for both its oral GLP-1 receptor agonist CT-996 and its injectable dual GLP-1/GIP receptor agonist CT-388.For further analysis, see Vital Signs: Roche’s second obesity hit.

Genentech, a Roche Group member, announced ​ this week that its investigational oral, glucagon-like peptide-1 (GLP-1) receptor agonist CT-996 showed good results at phase 1, with a 6% reduction in weight at 4 weeks compared with placebo. Roche acquired CT-996 as part of its $2.7 billion acquisition of Carmot Therapeutics, a biotech based in Berkeley, California, along with a daily and a weekly, injectable GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. All of the three candidate therapies acquired as part of Roche’s takeover of Carmot are designed to treat obesity alone or in combination with type 1 or type 2 diabetes. The daily, injectable GLP-1/GIP receptor agonist is at phase 2 and the other two candidates at phase 1. Successful phase 1 results for the weekly GLP-1/GIP receptor agonist CT-388 were announced ​ in May. The phase 1 study of CT-996 has three sections in total and two, including 65 participants with obesity, but not diabetes, have now been finished. The third part of the trial will begin later this year, again in people with obesity but not diabetes. Promising early weight loss results The topline results from the first two sections showed a reduction in weight loss of 7.3% in the treatment group versus 1.2% in the placebo group. "We are pleased to see the clinically meaningful weight loss in people treated with our oral GLP-1 therapy CT-996, which could eventually help patients address both chronic weight management and glycemic control indications,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, in a press statement. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “Following our data for CT-388, this is the second positive readout in less than three months from our growing metabolic pipeline, which includes both oral and injectable options to address patients' needs across a spectrum of related diseases.” Novo Nordisk’s oral GLP-1 semaglutide achieved a 12.7% reduction in weight (after adjusting for placebo) in a phase 3 trial, but this reduction was after 68 weeks, suggesting that Roche’s candidate has potential. The safety and tolerability of CT-996 were similar to that of other GLP-1 receptor agonists and the research team did not see any unexpected side effects or safety issues. Keeping up with the competition ​ The weight loss drug market has exploded since the approval ​ of Novo Nordisk’s GLP-1 receptor agonist Wegovy (semaglutide) for weight loss in 2021, followed by Eli Lilly’s combined GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist Zepbound ​ (tirzepatide) in 2022. The two companies have profited enormously from these products since their approval and many other biotech and pharma companies are now working on new weight loss drugs, both with a GLP-1 component and without. For example, Pfizer’s oral GLP-1 receptor agonist danuglipron ​, currently at phase 2. Roche’s acquisition of Carmot last year has allowed them to join the increasingly crowded weight-loss drug market, but whether they can truly compete with other players in the space like Novo Nordisk and Eli Lilly remains to be seen. While these early results are promising, the Roche/Carmot candidate therapies are all at a fairly early stage and will need to show significant benefits in terms of weight loss, tolerability and/or convenience to be approved and make a profit down the line.