Roche terminates development of obesity drug preserving muscle

The rights to emugrobart have been returned to Roche's subsidiary, Chugai Pharmaceutical

It was shown that the possibility of reaching the weight-loss goal decreases with a GLP-1 and GIP combination strategy

Roche, which has been working to expand into the obesity treatment market, has discontinued development of some of its pipeline.

An anti-myostatin antibody, intended to offset muscle loss during weight loss when combined with incretin-based therapies, was assessed as unlikely to achieve the expected level of efficacy in an interim analysis of a Phase 2 clinical trial.

However, the development of key obesity pipelines, such as the GLP-1/GIP dual agonist 'enicepatide' and the amylin analog 'petrelintide', is continuing. As these two candidates have recently yielded consecutive positive Phase 2 results, Roche appears to be streamlining its obesity pipeline.

Termination of 'emugrobart' Development for Obesity Indication

According to industry sources on the 29th, Chugai Pharmaceutical, a Japanese pharmaceutical company under the Roche Group, announced it will terminate development of emugrobart (GYM329) for the obesity indication. Consequently, Roche will return its rights to emugrobart to Chugai Pharmaceutical.

Emugrobart is a myostatin-targeted antibody therapeutic that was being developed as a subcutaneous injection formulation.

Myostatin is a protein that inhibits skeletal muscle growth. By targeting it, the drug had been developed under a strategy to reduce the loss of muscle mass that can occur during obesity treatment.

The decision to halt development resulted from a comprehensive evaluation of the data secured to date, including the interim analysis of the Phase 2 GYMINDA study currently being conducted in obese and overweight patients.

The GYMINDA study evaluated the efficacy and safety of combining a GLP-1/GIP receptor agonist with emugrobart. Based on the interim analysis, Roche determined that achieving the pre-specified, clinically meaningful weight-loss goal would be difficult.

However, safety issues did not cause the discontinuation of development. According to Chugai Pharmaceutical, emugrobart was well-tolerated, and no new safety signals were observed.

Emugrobart is a candidate substance discovered by Chugai Pharmaceutical, and Roche has led its development. In the obesity field, Roche has been evaluating emugrobart as a combination strategy to add a muscle-preservation effect to the weight-loss effect of GLP-1 class drugs.

In fact, when Roche announced the acquisition of the US biotech company Carmot Therapeutics in 2023, it highlighted the possibility of combining the incretin candidates it would acquire with its own pipeline aimed at preserving muscle mass.

Although the development of emugrobart for obesity has been halted, the candidate substance itself is not disappearing.

After regaining the rights from Roche, Chugai Pharmaceutical has begun preparing to resume development targeting spinal muscular atrophy (SMA). The company is also reviewing a possible out-licensing agreement (technology export). However, Roche suspended development of emugrobart for SMA and facioscapulohumeral muscular dystrophy (FSHD) in March.

Key candidates under development... Phase 2 achievements of 'enicepatide'

Despite discontinuing emugrobart development, Roche's key obesity pipeline has recently released consecutive positive clinical results.

On the 22nd, Roche disclosed the results of the Phase 2 CT-388-104 study of the GLP-1/GIP dual receptor agonist enicepatide (CT-388).

In overweight and obese adults with type 2 diabetes, the group administered 24 mg of enicepatide saw an average reduction in glycated hemoglobin (HbA1c) of 2.65 percentage points at week 48. In patients whose baseline HbA1c exceeded 8.5%, it decreased by 4.13 percentage points.

At the same dose, the average body weight decreased by 15.5% over 48 weeks. Roche explained that weight loss had not plateaued even at the 48-week mark. Safety and tolerability profiles were similar to those observed with existing incretin-based therapies, and Roche identified no new safety signals.

Enicepatide is a novel drug candidate acquired from Carmot Therapeutics. At the time of the acquisition announcement, Roche offered an upfront payment of $2.7 billion and up to $400 million in additional milestone payments. With the acquisition of Carmot, Roche secured an obesity and diabetes pipeline that includes not only enicepatide but also the oral GLP-1 candidate CT-996.

The development of the amylin analog petrelintide is also ongoing.

In March, Roche unveiled the results of the Phase 2 ZUPREME-1 study for petrelintide. Evaluated in 493 overweight and obese patients, the maximum average weight loss rate at week 42 was 10.7%. The placebo group showed a 1.7% reduction.

At the maximum effective dose, no cases of vomiting occurred, and no patients discontinued treatment due to gastrointestinal adverse events. Roche is further developing petrelintide both as a monotherapy and as a combination therapy with other obesity treatments.