Regeneron’s Pasatru shows no new bone lesions in adult FOP patients between weeks 56 and 84 of OPTIMA

Regeneron has reported positive 84 week results from the Phase 3 OPTIMA trial of Pasatru (garetosmab-grts) in adults with fibrodysplasia ossificans progressiva (FOP). The longer term data showed that the benefit seen earlier was maintained, with no new abnormal bone growth and a significant reduction in flare-ups. They were presented in a late breaking oral session at the American Society for Bone and Mineral Research Annual Meeting. The US Food and Drug Administration recently approved Pasatru on the strength of a 56 week placebo controlled trial, for reducing new heterotopic ossification (HO) lesions and clinician assessed flare-ups in adults with FOP. Pasatru is a fully human monoclonal antibody derived from Regeneron’s VelocImmune® technology. It binds to the Activin A protein and blocks its signalling. Regeneron scientists identified Activin A as a critical driver of HO lesions in people with FOP.

Professor Richard Keen, director of the Metabolic Bone Disease Centre at the Royal National Orthopaedic Hospital in London and global primary investigator of OPTIMA, said FOP is a devastating and relentless condition in which every flare-up can bring anxiety about new abnormal bone growth and lost mobility. He said patients urgently need long term control over new HO lesions and flare-ups to give them peace of mind. In his view, the 84 week data show sustained, disease modifying control alongside a generally well tolerated safety profile, which matters to adults living with FOP.

OPTIMA is a global, multicentre, randomised, double blind, placebo controlled trial that enrolled 63 people with FOP aged 18 and over. Participants received intravenous Pasatru at 10 mg/kg, Pasatru at 3 mg/kg, or placebo once every four weeks for 56 weeks. Of those, 58 completed the double blind extension phase to at least week 84.

At 56 weeks, the trial met its primary endpoint, with a reduction of 90 per cent or more in new HO lesions and a dramatic fall in clinician assessed flare-ups. Detailed results from that analysis were recently published in The Lancet. The endpoints were then assessed again at 84 weeks. Between week 56 and week 84, CT scans showed no new HO lesions in patients on Pasatru, compared with nine new lesions on placebo. One lesion in the 3 mg/kg group that had been detected at week 56 could no longer be seen at week 84. New clinician assessed flare-ups were also lower than on placebo, with one in the 10 mg/kg group, 14 in the 3 mg/kg group and 17 on placebo.

Through week 84, both doses had a generally well tolerated safety profile, in line with what was seen at 56 weeks. At 56 weeks, the most common adverse reactions, affecting at least 10 per cent of adults treated with Pasatru, were abscess, acne, increased hair growth, loss of eyebrow or eyelash hair, oral ulcers, nosebleeds, folliculitis, nail infection and rash. At 84 weeks, the most common treatment emergent adverse events were acne in the 10 mg/kg group and nosebleeds in the 3 mg/kg group, all of them non severe. Treatment emergent bleeding events were less frequent in the 10 mg/kg group than in the 3 mg/kg or placebo groups.

Skin and soft tissue infections rose with dose, occurring in 33 per cent of patients on placebo, 53 per cent on 3 mg/kg and 78 per cent on 10 mg/kg. All were resolved with further management, and no patient stopped treatment because of an infection. No deaths were reported in the trial.

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Related Topics and Keywords

bone lesions, FOP patients, OPTIMA, Pasatru, Regeneron, Regeneron's Pasatru