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Chakravarthy gets asked “all the time” whether Roche left it too late to jump into the obesity race, but insists “the answer is categorically no.” Roche is holding out hopes that its injectable obesity prospect could eventually demonstrate 25% weight loss in late-stage trials, the pharma’s head of metabolism R&D has told Fierce Biotech.The Swiss Big Pharma imported a pipeline of three molecules as part of its $2.7 billion acquisition of Carmot Therapeutics at the end of last year, including an injectable dual GLP-1/GIP receptor agonist dubbed CT-388.The candidate has already demonstrated average placebo-adjusted weight loss of 18.8% over 24 weeks in a phase 1b study, and Roche is using the European Association for the Study of Diabetes Annual Meeting in Madrid, Spain this week to take a deeper dive into the data.Talking to Fierce from the sidelines of the conference, Manu Chakravarthy, M.D., Ph.D., Roche’s Global Head of Cardiovascular, Renal and Metabolism Product Development, said the pharma has ambitions to demonstrate even greater weight loss in later-stage studies. “If we continue to see the trajectories that we're seeing in our ongoing studies, we could be looking at roughly 20, 25% body weight loss, which is going to be in line with what bariatric surgery does,” Chakravarthy said in the interview.For comparison, Novo Nordisk’s blockbuster GLP-1 agonist Wegovy achieved 14.9% average weight reduction in the 68-week STEP-1 phase 3 trial, while another study called OASIS showed 15% weight loss over the same period. Meanwhile, Eli Lilly’s dual GIP/GLP-1 agonist Zepbound was shown to induce 22.9% weight loss over the far longer time frame of 176 weeks.Roche already moved CT-388 into a phase 2 study in July, but Chakravarthy stressed that even if the company can eventually demonstrate 25% weight loss, this wouldn’t be seen until a phase 3 trial due to the longer time frame involved.“With the high dose option with the right patient population we can, in fact, aspire to a 25% or more weight loss,” he said. Because if you're on the trajectory from close to 19% in six months —most obesity trials run for 72 weeks, sometimes up to 100 weeks.”“So we have a lot of room here that we have to explore,” Chakravarthy added. “But the trajectory is very encouraging for us.”With the injectable obesity market currently dominated by Novo and Lilly, does Roche really think it can carve out its own space?While acknowledging it’s “a fair question,” Chakravarthy pointed to CT-388’s “signaling bias” as setting it apart from the competition.“It is the only molecule today that we are aware of that is dually biased, meaning it is signaling for [cyclic AMP] without ß-arrestin on both the GLP-1 receptor and the GIP receptor,” he explained. “We think that's a very unique attribute.” The approach is intended to achieve greater weight loss and glycaemic control plus a more favorable tolerability profile—leading Roche to continue to tout CT-388 as “potentially best-in-class.”“What was reassuring is that we're seeing that level of efficacy, while the safety and the tolerability is no worse than anything else that's out there,” Chakravarthy explained about the data shared at this week’s conference. “An integrated approach”At the same event, Roche is presenting additional data from a phase 1 trial of CT-996, an oral GLP-1 that also originated at Carmot. In July, the pharma announced 7.3% weight loss from the trial after four weeks.More broadly, Roche also thinks it can stand out from the obesity crowd with an “integrated approach” that takes account of these molecules in development and offers patients digital health support, Chakravarthy said.“When we actually go out into the market space, we're actually offering a comprehensive suite of solutions, not just a one-off ‘Oh, here's an injectable, here's an oral, go figure it out’ kind of thing,” he said. “We are looking at it in a very long-term view.” “We can also bring in the oral [drug] as a maintenance directly for those that have finished their injectable induction phase, right? So there is multiple ways of mixing and matching,” he said.This integrated strategy also encompasses the planned kick-off of a phase 2 trial next year of CT-388 in combination with Roche’s anti-myostatin antibody, RO7204239, to see if together they can reduce the muscle loss typically associated with losing weight.Chakravarthy admitted he gets asked “all the time” whether Roche left it too late to jump into the obesity race, but insisted “the answer is categorically no.”“We have, like, four billion people in the world that are going to become overweight or obese in the next half a decade or so,” Chakravarthy added. “Fundamentally, I just don't think that two companies currently can supply the world's medicines for all those people.”

Roche is best known for the cancer drugs that still account for much of its drug revenue. But the Swiss pharmaceutical giant spent much of its latest quarterly earnings call fielding questions about a pair of experimental weight loss medicines that have fast become important to its future growth.Roche last year acquired those medicines in a $2.7 billion deal for biotechnology company Carmot Therapeutics. One, CT-388, is an injectable therapy, while the other, CT-996, is a pill. Since May, both have since shown the potential in early trials to spur significant weight loss, adding billions to Roches market value and making the company a surprise player in one of the most lucrative areas of drug research.Its going to be a huge market, CEO Thomas Schinecker said on a conference call. By 2035, about 50% of the worlds population will be obese.Like Amgen, Pfizer and biotechnology company Viking Therapeutics, Roche aims to develop a rival to fast-selling medicines from Eli Lilly and Novo Nordisk. Those drugs, Zepbound and Wegovy, have proven powerfully effective at lowering weight. Studies have pointed to other health benefits for these and other so-called incretin medicines as well. But there is room for improvement, as current therapies are injected once-weekly, come with gastrointestinal side effects and can cause people to lose muscle mass along with weight. Demand is currently outstripping the available supply as well.In an earnings presentation Thursday, Roche said its injectable therapy has best-in-class potential, having helped people lose nearly 20% of their body weight over six months, when adjusted for a placebo. Schinecker also noted that Roche can use its existing manufacturing network to quickly scale up production of its oral drug if testing is successful. A third therapy, dubbed CT-868, is specifically designed for Type 2 diabetes, he said.But Roches drugs are well behind others, which could make it difficult for the company to stand out. A Phase 2 study of the injectable medicine will begin this quarter, with a mid-stage study for the oral therapy following next year. Large, late-stage trials would follow, meaning by the time the drugs get to market, one analyst noted, they could be the fourth or fifth of their kind available.Schinecker responded that certain characteristics of Carmots drugs make them unique, which in turn could lead to differentiating results. Roche also acquired an array of assets in the deal, some of which are aimed at separate, unspecified targets. The company intends to combine some of them with drugs from its in-house pipeline to help preserve muscle mass.Schinecker additionally claimed, without offering specifics, that Roche can get to market much more quickly than investors assume and is pumping more money in manufacturing ahead of time.There are many opportunities that we believe can [help] differentiate, he said. We can be very fast on this, and be a very competitive player in space.The company is open to doing other obesity-related deals as well, with Schinecker noting last years Carmot buyout is a template of something you could imagine for this year, depending on the cost and availability of potential assets.Roche will present more data from early-stage trials of CT-388 and CT-996 at a medical meeting in September. That month, on a scheduled investor day, the company also intends to reveal more about its obesity drug development strategy.Beyond obesity, Roche is interested in how incretin drugs may curb systemic inflammation, making them potentially worth exploring as part of combination therapies for neurological conditions like Alzheimers and Parkinsons, said Teresa Graham, the head of the companys pharmaceuticals division.Roche shares climbed about 3% in Thursday trading. '

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.