Roche announces Phase 2 trial in FSHD

The drug, GYM329, aims to boost muscle growth

Roche, the Swiss pharmaceutical giant, has announced that it is launching an international Phase 2 clinical trial for facioscapulohumeral muscular dystrophy (FSHD). The trial, which is called MANOEUVRE, will take place in Denmark, Italy, the UK, and US, and is planned to begin enrolling patients by the end of 2022. It will evaluate GYM329 (RO7204239), an investigational anti-myostatin antibody targeting muscle growth, in individuals living with FSHD.

A clinical trial is a scientific experiment. The drug being tested has not yet been proven to work. Patients participating in the trial will help to determine if the drug is safe and effective. The trial is not yet enrolling patients. In the meantime, patients who are interested should share this letter from Roche with their doctors and have a conversation about whether the trial would be appropriate for them.

What is GYM329?

GYM329 is an investigational anti-myostatin antibody that is designed to target skeletal muscles, potentially increasing their size and growth. Myostatin plays an important role in the regulation of skeletal muscle size by controlling its growth. Inhibiting myostatin may help muscles grow in size and strength. GYM329 has been engineered as a “recycling” and “sweeping” antibody, which means that it may be more efficient at removing myostatin from the blood compared to a conventional antibody.

Where and when?

Roche says that around 10 sites have been selected to participate in the study in four countries: Denmark, Italy, the UK, and the United States. Enrollment is anticipated to start later in 2022.

If you are interested, here is what you can do now:

• Share this letter from Roche with your physician and discuss your treatment options.
• Get a genetic test to confirm your FSHD, if you haven’t previously done so.
• Visit clinicaltrials.gov for updates; look under Locations to see if a site near you has begun recruiting.
• Sign up to receive email alerts from the FSHD Society. Click on the link below.

Lessons from past clinical trials

The FSHD community may recall previous clinical trials for anti-myostatin drugs, such as MYO-029 and ACE-083. These drugs are based on antibodies that interfere with myostatin. In a Phase 2 clinical trial of FSHD patients, ACE-083 resulted in a 15 percent increase in volume of the muscles that were injected with the drug. However, over the 6 months of that trial, patients receiving ACE-083 did not show a significant improvement in muscle function compared to controls who received a placebo.

Interestingly, a Phase 2 clinical trial of a different type of drug, losmapimod, by Fulcrum Therapeutics, suggested that six months is not long enough to show a benefit in FSHD (using current measurement methods). The losmapimod Phase 2 trial was originally planned to last 6 months, but because of the COVID-19 pandemic, the trial was doubled in length to 12 months. That turned out to be a stroke of luck. While the data collected at 6 months did not show any significant difference between the treated and placebo groups, data collected at 12 months did show a small but significant benefit.

Roche’s MANOEUVRE trial appears to have taken this lesson into account, as it will dose patients for a full year.

Details of the trial

To be eligible for the MANOEUVRE trial, individuals must have FSHD1 or FSHD2, be between 18 and 65 years of age, and able to walk independently. The study plans to enroll approximately 48 participants. Individuals will be randomly assigned to receive GYM329 or a placebo every 4 weeks via a subcutaneous injection (into the fatty layer just below the skin). The study will be double-blinded, meaning that neither the participant nor the study team will know who is receiving GYM329 or the placebo.

At various times throughout the trial, participants will be asked to take part in various assessments, including an MRI, muscle function and strength tests, completing questionnaires, and other evaluations. At the beginning of the study and then every 6 months thereafter, the participants will be asked to wear a digital device for a 4-week period that will help measure everyday upper and lower limb movement and capture changes to activities during normal daily living. The study results will be analyzed after all participants have completed 52 weeks of treatment.

The company says after participants have completed the 52 weeks in the double-blind, placebo-controlled trial, they can opt to continue for an additional 52 weeks in what is called an open-label study, in which all individuals will receive GYM329 and continue to be evaluated.

Results from the MANOEUVRE study will determine whether GYM329 should proceed to a Phase 3 trial. The Phase 3 trial will be designed to show whether the drug provides a significant clinical benefit in a larger group of patients. Data from Phase 3 trials are reviewed by the regulatory agencies such as the U.S. Food and Drug Administration and European Medicines Agency to determine whether a drug can be approved to go on the market.