US-based Alnylam Pharmaceuticals has started the ENDEAVOUR Phase III clinical trial of revusiran in transthyretin (TTR)-mediated familial amyloidotic cardiomyopathy (FAC).
The randomised, double-blind, placebo-controlled, global trial is designed to evaluate the efficacy and safety of revusiran in patients with FAC, which is one of the predominant clinical manifestations of TTR-mediated amyloidosis (ATTR).
Around 200 FAC patients with a documented TTR mutation, including V122I or other mutations will be enrolled in the trial and they will be randomised 2:1, revusiran:placebo, with revusiran administered subcutaneously at 500mg daily for five days then weekly for 18 months..
Alnylam executive vice-president and chief medical officer Akshay Vaishnaw said: "Initiation of ENDEAVOUR highlights our continued execution on our product development strategy for our genetic medicines pipeline and, together with our APOLLO Phase III trial with patisiran for the treatment of familial amyloidotic polyneuropathy, represents our commitment to develop innovative medicines for patients afflicted with ATTR."
The trial's co-primary endpoints are the change compared to baseline in 6-minute walk distance (6-MWD) and the percent reduction in TTR burden between placebo- and revusiran-treated patients at 18 months.
After dosing of the first patient in the trial, Alnylam will be eligible to receive a milestone payment of $25m from Genzyme.
The secondary endpoints include a composite endpoint of cardiovascular mortality and cardiovascular hospitalisation, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), CV mortality, CV hospitalisation and all-cause mortality.