#AANAM — Phase 1b/2 Trial Of RG6206 in Boys With DMD Supports Safety, Positive Muscle Effects

RG6206 (BMS-986089), a blocker of muscle growth-inhibitor myostatin, is safe to use in boys with Duchenne muscular dystrophy (DMD), results from a Phase 1b/2 trial show. A Phase 2/3 trial of the drug (NCT03039686) is actively recruiting patients.

Moreover, the results showed that the compound was able to reduce the amount of free myostatin in DMD patients by at least 77%.

The findings, “A Phase 1b/2 Study of the Anti-Myostatin Adnectin RG6206 (BMS-986089) in Ambulatory Boys with Duchenne Muscular Dystrophy: A 72-Week Treatment Update,” were presented in a poster session at the 2019 American Academy of Neurology (AAN) annual meeting, taking place through May 10 in Philadelphia.

RG6206 is an inhibitor of the protein myostatin. Myostatin inhibits muscle growth, so the logic is that inhibiting this protein could promote muscle growth, which could be beneficial for DMD patients.

The phase 1b/2 trial (NCT02515669) primarily aimed at determining the safety and tolerability of RG6206.

It included 43 boys with DMD, ages 5–10, all of whom were able to walk. For the first 24 weeks of the trial, the patients were randomly assigned to receive either a subcutaneous (under-the-skin) injection of 4–50 mg of RG6206 or a placebo.

Then, in a 48-week, open-label (that is, not blinded) extension of the trial, all patients were given RG6206.

After the 24-week period, the most common adverse events reported were reactions in the injection site. These were described as “mild to moderate” and cleared up without the need to change the treatment.

There weren’t any notable changes in clinical laboratory tests, vital signs or heart function. In one patient at one timepoint, antibodies against RG6206 were detected; however, these weren’t associated with any adverse reactions.

The medication reduced myostatin levels in all patients by at least 77%. Patients at the high-dose 35 mg had up to 97% reduction in myostatin levels.

At 72 weeks, lean body mass (LBM) increased in boys treated with RG6206. This data was compared with boys with DMD in the Collaborative Trajectory Analysis Project (cTAP) who had not received any treatment. Researchers reported there was a decrease in LBM in this cohort.

Moreover, at week 24, dose group pooling showed that boys who received the treatment showed a 3.85% increase in LBM and a 5.49% increase in contractile cross-sectional area (CSA) of the right thigh.

Overall, the study suggests that RG6206 can be used safely in boys with DMD. Most of the patients (41) are currently enrolled in a 228-week open-label extension of the trial, and a Phase 2/3 trial of RG6206 (NCT03039686) is actively recruiting patients worldwide.