Roche culls myostatin candidate from obesity pipeline

Roche has abandoned the development of one of its obesity candidates, emugrobart, and returned rights to originator Chugai Pharma.

The subcutaneously administered anti-myostatin antibody – also known as GYM329 – is among a clutch of myostatin-targeting therapies coming through development that are designed to promote muscle growth in obesity, offsetting the reduction in muscle mass that can accompany current weight-loss drugs.

Roche was originally developing the drug for multiple indications, including muscle-wasting diseases spinal muscular atrophy (SMA) and facioscapulohumeral muscular dystrophy (FSHD), but abandoned those two programmes earlier this year. Now, with the demise of the obesity programme, it has surrendered all interests in the drug.

Emugrobart had been billed as a potential best-in-class myostatin inhibitor because, unlike other antibodies that bind to the mature, active form of the protein, it targets the inactive (latent) and precursor forms, cutting its activity off without affecting the activity of similar proteins in the TGF-beta family, like GDF11 or activin A.

The hope was that this mechanism could enhance efficacy and reduce the risk of side effects compared to active myostatin-targeting drugs like Scholar Rock's apitegromab and Biohaven Pharma's taldefgrobep alfa, and Eli Lilly's bimagrumab. However, Chugai said today that clinical trials in obesity, including the phase 2 GYMINDA study, had failed to make a convincing case for the drug.

"In the GYMINDA study, the efficacy and safety of emugrobart in combination with GLP-1/GIP receptor agonists were evaluated in patients with obesity/overweight," said the Japanese drugmaker. "It was concluded that achieving the pre-specified efficacy objectives of clinically meaningful weight loss is unlikely."

Roche has made developing drugs for weight-loss and obesity a key part of its R&D strategy, with several candidates in clinical development and an ambition to become a top three player in the category, which is currently dominated by Novo and Eli Lilly.

Other candidates in its pipeline include injectable GIP/GLP-1 agonist enicepatide, injectable amylin analogue petrelintide, and oral GLP-1 agonist CT-996, which are in late-stage clinical development and among a series of around 20 new products that Roche hopes to launch by the end of the decade.

It's not the end of emugrobart, as Chugai – which is majority owned by Roche – has said it will resume development of the drug for SMA whilst also looking for other out-licensing partners.

"Based on emugrobart's subcutaneous […] administration, obtained safety profile, pharmacodynamics, clinical signals (including long-term data), and phase 3 study design modifications, Chugai has identified an opportunity to support a phase 3 study in SMA," it added.