Regeneron Pharmaceuticals has reported sustained disease control with Pasatru (garetosmab-grts) in adults with fibrodysplasia ossificans progressiva (FOP), with 84-week data showing no new abnormal bone lesions in treated patients at the assessment point and fewer disease flare-ups than with placebo.
The findings from the Phase 3 OPTIMA trial were presented during a late-breaking oral session at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting. The longer-term results extend earlier findings that led to the drug’s recent approval by the US Food and Drug Administration (FDA), based on 56-week data.
FOP is a rare, debilitating condition in which bone forms in muscles, tendons and other soft tissues, progressively restricting movement. Disease flare-ups can trigger new bone formation and further loss of mobility, making sustained control a critical treatment goal.
“FOP is a devastating, relentless condition in which every flare-up can bring anxiety around potential new, abnormal bone growth and resulting loss of mobility,” said Professor Richard Keen, Director of the Metabolic Bone Disease Centre, Royal National Orthopaedic Hospital, London, and global primary investigator of the OPTIMA trial.
“What patients urgently need is long-term control over new HO lesions and flare-ups to help bring peace of mind. The 84-week data from the Phase 3 OPTIMA trial demonstrate sustained disease-modifying control alongside a generally well-tolerated safety profile, which is important for the adult FOP community.”
The global, multicentre OPTIMA trial enrolled 63 adults aged 18 and older with FOP. Participants were randomly assigned to receive intravenous Pasatru at 10 mg/kg, Pasatru at 3 mg/kg, or placebo every four weeks for 56 weeks. A total of 58 participants completed the double-blind extension phase through at least week 84.
At week 56, the trial met its primary endpoint, demonstrating a reduction of 90% or more in new heterotopic ossification (HO) lesions, alongside a substantial reduction in clinician-assessed flare-ups. Detailed results from the 56-week analysis were recently published in The Lancet.
The extended analysis showed that no new HO lesions were detected at week 84 among Pasatru-treated participants from the week 56 assessment, compared with nine new lesions in the placebo group, as measured by computed tomography (CT) scans.
One lesion previously detected at week 56 in the Pasatru 3 mg/kg group was also no longer detectable at week 84.
Clinician-assessed flare-ups remained lower in the treatment groups than in the placebo group. Researchers recorded one new flare-up in the Pasatru 10 mg/kg group, compared with 14 in the 3 mg/kg group and 17 in the placebo group.
The results suggest sustained suppression of new abnormal bone formation, particularly with the higher dose, although the trial's relatively small patient population remains an important consideration when interpreting the findings.
Both Pasatru doses maintained a generally well-tolerated safety profile through week 84, consistent with the findings at week 56. However, the extended data also highlighted a dose-dependent increase in skin and soft tissue infections.
Such infections were reported in 33% of participants receiving placebo, 53% receiving Pasatru 3 mg/kg and 78% receiving Pasatru 10 mg/kg. All infections resolved with further management, and no participant discontinued treatment because of an infection.
At week 56, the most common adverse reactions, occurring in at least 10% of adults treated with Pasatru, included abscesses, acne, increased hair growth, madarosis (loss of eyebrow or eyelash hair), oral ulcers, nosebleeds, folliculitis, paronychia (nail infection) and rash.
By week 84, acne was the most common treatment-emergent adverse event among participants receiving Pasatru 10 mg/kg, while nosebleeds — all non-severe — were most common in the 3 mg/kg group.
