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.”