Chugai Revives Emugrobart as Roche Abandons it for Obesity

Chugai Pharmaceutical is preparing to revive emugrobart’s (GYM329) development for spinal muscular atrophy (SMA) just six months after Roche abandoned the program, citing new consideration of long-term clinical signals and modifications to a potential Phase 3 trial design. The reversal comes as Roche decided to discontinue a separate effort to develop the anti-myostatin antibody for obesity and return all drug rights to Chugai.

Chugai says it is preparing to resume SMA development while also exploring potential out-licensing opportunities with third parties.

The renewed interest in SMA coincides with the recent failure of emugrobart's obesity program. Roche evaluated the antibody in the Phase 2 GYMINDA study in combination with GLP-1/GIP receptor agonists in patients with obesity or overweight. An interim analysis and other available data led Roche to conclude that the study was unlikely to achieve its prespecified efficacy objective of clinically meaningful weight loss.

That finding effectively reverses the development strategy Roche outlined in March. When it stopped the neuromuscular programs, the company said there remained a strong scientific rationale for obesity because patients generally have more myostatin available for an anti-myostatin antibody to target than patients with neurodegenerative or muscle-wasting disorders. Roche therefore continued the obesity program even as it abandoned SMA and facioscapulohumeral muscular dystrophy (FSHD).

Roche discontinued development of emugrobart for SMA and FSHD in March following its assessment of Part 1 of the Phase 2/3 MANATEE trial in SMA and the Phase 2 MANOEUVRE trial in FSHD. At the time, Chugai said emugrobart demonstrated target engagement by reducing mature myostatin and had a favorable safety profile, but the effects on muscle growth and exploratory measures of functional efficacy did not justify Phase 3 development. The discontinuation was not driven by safety concerns, the companies said.

Chugai now says that since Roche's March decision, it has reassessed emugrobart based on its subcutaneous administration, safety and pharmacodynamic profile, clinical signals including long-term data, and modifications to the Phase 3 study design. Those factors, it says, have identified an opportunity to support a Phase 3 study in SMA.

Chugai did not disclose details of the proposed Phase 3 design changes or specify which long-term clinical findings contributed to its reassessment.

Emugrobart is a subcutaneously administered anti-latent myostatin "sweeping" antibody designed to inhibit myostatin, a negative regulator of skeletal muscle growth.