Clementia Pharmaceuticals has announced top-line results from its Phase 2 clinical trial investigating palovarotene for the treatment of fibrodysplasia ossificans progressiva (FOP).
FOP is a rare, serious disease, in which an accumulation of heterotopic ossification (HO, extraskeletal bone) in muscle and soft tissue progressively hinders movement by locking joints, which in turn leads to loss of function, physical disability, and risk of early death.
Several positive trends were observed in this 40-subject placebo-controlled study, including palovarotene-related reductions in the proportion of subjects who developed new HO, reductions in volume of new HO, reductions in patient-reported pain associated with flare-ups, and reductions in the time to resolution of FOP-related flare-ups, though none reached statistical significance.
All subjects completed the 12-week study and enrolled into the open-label extension trial.
Palovarotene was found to be well-tolerated in the subjects.
Clementia CEO Clarissa Desjardins said: “We would like to thank the patients, their families, the investigators, and their research teams.
“Developing a potential treatment for FOP is our passion and our goal, and we will continue to press forward as rapidly and rigorously as possible to deliver a much needed potential therapy for all FOP patients.”
The Phase 2 trial of 12 weeks randomised subjects to three dose groups: 10mg palovarotene for two weeks followed by 5mg for 4 weeks (10/5), 5mg for two weeks followed by 2.5mg for four weeks (5/2.5), or placebo.
Treatment commenced within seven days of the onset of a flare-up with evaluations made at baseline, at the end of treatment (six weeks), and after a six-week observation period (12 weeks).
Subjects on placebo were at 2.6 times greater risk of forming HO than those on palovarotene 10/5mg treatment. The patients on either palovarotene regimen with new HO formed less HO than those on placebo.
Subjects on the 10/5 regimen found a significant improvement in pain linked with flare-ups and a reduction in the duration of overall flare-up symptoms.
Even though a dose-related increase in the incidence of mucocutaneous adverse events was observed, no subject required a reduction in dose due to tolerability issues nor was discontinued from the study.
Complete results of the Phase 2 study are expected to be published in 2017.
Clementia continues to gather significant additional data in the Phase 2 extension trial and in the ongoing observational Natural History Study.
Data from these studies will inform the design of a Phase 3 registration study, slated to commence in 2017.