RG6206 (talditercept alpha, anti-myostatin adnectin), also known as BMS-986089 and RO7239361, is a myostatin inhibitor originally developed by Bristol-Myers Squibb and later licensed to Roche. It was being investigated as a therapy for Duchenne muscular dystrophy (DMD) but has now been discontinued by Roche.
How RG6206 works
Like most cells, muscle cells or myocytes divide to form new cells or regenerate worn-out muscle tissue. The muscle cell division process occurs in multiple stages starting from the myoblasts that finally differentiate into myocytes. Myostatin, also known as growth differentiation factor 8 (GDF 8), is an inhibitor that prevents the differentiation of myoblasts into myocytes, hindering muscle growth so that muscles do not grow too large.
People with DMD show symptoms of low muscle mass and muscle wasting. RG6206 binds to myostatin and prevents it from acting on muscle tissue. This helps the muscle tissue to grow and differentiate. Scientists think that inhibiting myostatin in these people using therapeutics such as RG6206 can help increase muscle mass.
RG6206 in clinical trials
A Phase 1 randomized single and multiple-ascending dose study (NCT02145234) of RG6206 was completed in February 2016. The study found that RRG6206 was well-tolerated in DMD patients who could still walk. The treatment also helped in increasing thigh muscle mass and total lean body mass.
A Phase 1 open-label randomized clinical trial (NCT03100630) to study the safety and efficacy of RG6206, and to compare its bioavailability when injected under the skin in the arm, thigh, and abdomen in healthy adults was completed in 2017. This trial showed good tolerability of RG6206.Â
A Phase 1/2 multi-site randomized clinical trial (NCT02515669, nicknamed THUNDERJET) to evaluate the safety and efficacy of multiple ascending doses of RG6206 injected under the skin in DMD patients that are still able to walk was discontinued in November of 2019. Participants received either the treatment or placebo for 24 weeks in a double-blind phase of the study followed by a 48-week open-label phase of the study where all participants received the therapy. Preliminary results of the study were presented at the 2019 American Academy of Neurology (AAN) annual meeting and the 2019 European Academy of Neurology (EAN) conference. Both presentations stated that the only adverse events have been injection site irritation which cleared up without any changes to treatment and that patients showed a 77-97% reduction in free myostatin.
A Phase 2/3 clinical trial (NCT03039686 called SPITFIRE) to further assess the safety, efficacy, and tolerability of RG6026 recruited 166 boys, ages 6 to 11, with DMD, who could still walk. Study participants received either of two doses of RG6206 or a placebo for 48 weeks. Analysis of preliminary results of the study indicated that the study was not likely to meet its primary endpoint of changes in North Star Ambulatory Assessment score.
Based on the results of this analysis, Roche announced that it will be discontinuing both the SPITFIRE and THUNDERJET trials.
Other information
Pfizer was also developing a myostatin inhibitor called domagrozumab (PF-06252616), but it was discontinued in August 2018 as patients recruited for the clinical trial (NCT02310763) testing it were not showing significant improvements in muscle function.
Last updated: Nov. 13, 2019
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