Roche has discontinued a phase 2/3 trial of RG6206 after a futility analysis showed that the drug was “highly unlikely” to demonstrate clinical benefit in patients with Duchenne muscular dystrophy (DMD).1 The anti-myostatin adnectin protein agent was being studied in the phase 2/3 SPITFIRE trial, as well as the phase 1b/2 THUNDERJET trial.

“While the science and large body of research gave us hope that RG6206 would have offered people living with DMD and their families a safe and effective treatment option, the results of the SPITFIRE study at this time lead us to the difficult conclusion that this approach will not be successful,” Roche stated in a letter to the DMD community.1

SPITFIRE (NCT03039686) was a double-blind, placebo-controlled study that included 166 ambulatory boys (aged 6 to 11) with DMD who were randomized to receive 1 of 2 doses of RG6206 or placebo subcutaneously on specified days across a 48-week treatment period. Each patient was assessed from baseline on the North Star Ambulatory Assessment (NSAA) total score. Other secondary endpoints included various mobility measures, including change in 4 Stair Climb Velocity, 10M walk/run velocity, and 6 Minute Walk Distance. 

Trial inclusion criteria included the ability to walk without assistance, minimum NSAA score of at least 15 at screening, ability to walk up 4 stairs in 8 seconds or less, a weight of at least 15kg (33lbs), and a stable regimen of corticosteroids for DMD. Patients taking medications like androgens or human growth hormones or those who were need of a ventilator during the day were excluded from the trial. Additionally, patients who were unable to provide blood samples or receive injection under the skin were excluded.

The discontinuation of SPITFIRE also affects the THUNDERJET trial, which was an open-label extension study evaluating RG6206 in boys with DMD. While Roche has seemingly met a blockade in the search for treatment for DMD, there were previous indications made that the recently licensed myostatin inhibitor, formally known as BMS-986089, could potentially be studied for other neuromuscular disorders besides DMD. 
REFERENCE
1. Roche Genentech Releases Letter to DMD Community Announcing Discontinuation of Clinical Trials Program for DMD. Muscular Dystrophy Association. November 6, 2019. strongly.mda.org/roche-genentech-releases-letter-to-dmd-community-announcing-discontinuation-of-clinical-trials-program-for-dmd/. Accessed November 7, 2019.