Success for Clementia’s Phase II Fibrodysplasia Ossificans Progressiva trial
Posted: 18 October 2016 | | No comments yet
Palovarotene was well-tolerated, with all subjects completing the 12-week trial and enrolling into the open-label extension trial…
Clementia Pharmaceuticals noted several positive trends in their Phase II clinical trial investigating palovarotene for the treatment of fibrodysplasia ossificans progressiva (FOP), 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.
Palovarotene was well-tolerated, with all subjects completing the 12-week trial and enrolling into the open-label extension trial.
FOP is an extremely rare, serious disease in which an accumulation of heterotopic ossification (HO, extraskeletal bone) in muscle and soft tissue progressively restricts movement by locking joints leading to loss of function, physical disability, and risk of early death.
“The results closely mirror what was observed in previously reported animal studies with palovarotene,” said principal investigator, Frederick Kaplan, MD, Perelman School of Medicine at the University of Pennsylvania. “This study has considerably enhanced our knowledge of FOP and is a significant step forward for the entire FOP community.”
The 12-week Phase 2 trial randomized subjects to three dose groups: 10 mg palovarotene for 2 weeks followed by 5 mg for 4 weeks (10/5), 5 mg for 2 weeks followed by 2.5 mg for 4 weeks (5/2.5), or placebo.
Treatment was initiated within 7 days of the onset of a flare-up with evaluations made at baseline, at the end of treatment (6 weeks), and after a 6-week observation period (12 weeks). Subjects on placebo were at 2.6 times greater risk of forming HO than those on palovarotene 10/5 mg treatment, while those on either palovarotene regimen with new HO formed less HO than those on placebo.
Subjects on the 10/5 regimen reported a greater improvement in pain associated with flare-ups and a reduction in the duration of overall flare-up symptoms. 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 trial.
Phase III clinical trials
Data from these studies will inform the design of a Phase 3 registration trial, which is expected to start in 2017.
Many years of laboratory research paved the way for this clinical trial. A leading investigator, Maurizio Pacifici, PhD, director of Orthopedic Research at CHOP, and his collaborators first showed that palovarotene produces powerful biological effects in transgenic mouse models of human FOP and inhibits HO markedly. “Those results have provided the basis and rationale for testing