Clementia Pharma to file in 2019 for palovarotene based on Phase II data for prevention of heterotopic ossification in patients with fibrodysplasia ossificans progressiva.

Clementia Pharmaceuticals Inc. announced that it plans to submit a New Drug Application (NDA) for palovarotene to the FDA in the second half of 2019. Based on recent interactions between Clementia and the FDA, including a Type B meeting as part of palovarotene�s Breakthrough Therapy Designation, the FDA has agreed that available data would support filing of an NDA for palovarotene for the prevention of heterotopic ossification (HO) associated with flare up symptoms in patients with fibrodysplasia ossificans progressiva (FOP).

The FDA based its assessment on the efficacy and safety data available from the completed Phase II clinical program, which showed a statistically significant reduction in mean new HO volume, or bone volume, associated with flare-ups of FOP at 12 weeks as compared to placebo or untreated flare-ups. The data provided to the FDA included the results from Clementia�s Phase II studies, which were recently presented at ASBMR 2018.

In these studies, 92 palovarotene-treated flare-ups in 62 patients across three different dosing regimens were evaluated compared to 46 placebo or untreated flare-ups in 41 patients from the Company�s natural history study. Patients treated with palovarotene at the time of a flare-up demonstrated a greater than 70 percent reduction in mean new HO volume at 12 weeks compared to the untreated group. Further, the reduction in mean new HO volume among those treated with the episodic 20/10 mg dosing regimen (20 mg for 4 weeks starting at the time of a flare-up followed by 10 mg for 8 weeks) was statistically significant (p=0.02). Palovarotene was generally well tolerated across all dosing regimens of the Phase 2 clinical program. There were dose-related increases in retinoid-associated adverse events (AEs) with most being mild or moderate in severity, and only one patient discontinued participation in the study because of an AE.

Comment: Palovarotene is a retinoic acid receptor gamma agonist in-licensed from Roche Pharmaceuticals, where it was previously evaluated in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. Palovarotene has been shown to block bone formation in a variety of mouse models of FOP and is being investigated as a potential treatment for FOP.