Development

Chugai resurrects emugrobart in SMA after Roche exits following obesity failure

Chugai resurrects emugrobart in SMA after Roche exits following obesity failure

Japan-based Chugai Pharmaceutical (Tokyo: 4519) is preparing to resume development of emugrobart (GYM329) in spinal muscular atrophy (SMA) after Roche ended all future development of the anti-latent myostatin sweeping antibody, including discontinuing the Phase II GYMINDA obesity study following an interim analysis that indicated clinically meaningful weight loss was unlikely to be achieved. Under the terms of the arrangement, all rights previously licensed to Roche will revert to Chugai, which said it has initiated preparations to resume SMA development while also exploring potential out-licensing opportunities with third parties.

Chugai’s decision suggests it believes the totality of the clinical and pharmacodynamic evidence, together with modifications to the Phase III study design, may still support further testing in SMA.

The obesity discontinuation followed a comprehensive assessment of data from the ongoing Phase II GYMINDA study, a randomized, double-blind, placebo-controlled trial evaluating emugrobart in combination with the dual GLP-1/GIP receptor agonist tirzepatide in adults with obesity or overweight without diabetes mellitus. Chugai said it was concluded that achieving the pre-specified efficacy objectives of clinically meaningful weight loss was unlikely, though emugrobart was well tolerated and no new safety signals were observed.

Roche had already discontinued emugrobart in SMA and facioscapulohumeral muscular dystrophy (FSHD) in March 2026, following a rigorous assessment of data from the Phase II/III MANATEE study in SMA and the Phase II MANOEUVRE study in FSHD. In the MANATEE study, emugrobart in combination with risdiplam did not meaningfully improve motor function across ambulant and non-ambulant cohorts compared to risdiplam alone, and the discontinuation was not driven by safety findings. Chugai said at the time of the March discontinuation that the scientific rationale for continuing obesity development remained strong, citing differences in the metabolic disease setting.

Emugrobart binds specifically to the latent form of myostatin in a pH-dependent manner and employs sweeping antibody technology to reduce circulating myostatin levels by forcing internalization via Fc gamma receptors, thereby blocking myostatin-mediated inhibition of skeletal muscle growth and strength.

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Chugai said its decision to pursue SMA development is based on emugrobart's subcutaneous administration route, its obtained safety profile, pharmacodynamics, clinical signals including long-term data, and Phase III study design modifications that it said identified an opportunity to support a Phase III study in SMA.

In the SMA myostatin-inhibition space, Cambridge, Massachusetts-based Scholar Rock (Nasdaq: SRRK) has secured US FDA approval for Isembyld (apitegromab-mstn), making it the first approved muscle-targeted therapy for SMA. The approval covers adults and children aged two years and older who are receiving an SMN2-targeted treatment and was based on the Phase III SAPPHIRE trial, in which apitegromab improved motor function versus placebo in the primary efficacy population. Apitegromab is a fully human IgG4 monoclonal antibody that binds promyostatin and latent myostatin, blocking myostatin activation.

Chugai said it will determine next steps for emugrobart's SMA development with the aim of delivering medicines to patients as rapidly as possible, and is also focusing on anti-obesity drug discovery research across multiple modalities, with plans to advance several development candidates into clinical trials over the next few years.


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