Ipsen to pause dosing patients in the global Phase III (PVO-1A-301) study to evaluate the efficacy and safety of palovarotene in patients with fibrodysplasia ossificans progressiva.

Ipsen announced the decision to pause dosing patients in the global Phase III (PVO-1A-301) study designed to evaluate the efficacy and safety of palovarotene in patients with fibrodysplasia ossificans progressiva (FOP), as well as the ongoing Phase II (PVO-1A-202/204) extension studies. In both the Phase III and Phase II extension studies, palovarotene is dosed both chronically (daily) and episodically (during flare-ups). The decision to pause dosing patients in the trial is based on results of a futility analysis reviewed by the Independent Data Monitoring Committee (IDMC) as part of the prespecified interim analysis. The results of a futility analysis indicated that the Phase III FOP trial was unlikely to meet its primary efficacy endpoint (annualized change in new HO volume as compared with Natural History Study upon completion. Despite the results of the prespecified interim analysis, signals of encouraging therapeutic activity were observed in preliminary post-hoc analyses of the Phase III trial and shared with and acknowledged by the IDMC which is recommending not to discontinue the study. In its recommendations, the IDMC notes highly disparate results precluding a confident conclusion about futility. The IDMC also points out that the protocol-prespecified model may have negatively affected the efficacy analysis and shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment. The FDA partial clinical hold for the pediatric population under the age of 14 for FOP and multiple osteochondromas (MO) issued on 4 December 2019, remains in effect. Ipsen will pause dosing patients in the trials and conduct further assessment of the complete data set. Based on the IDMC’s observations and recommendations, Ipsen will discuss these findings with regulatory authorities to determine the path forward for the palovarotene program in FOP.