27 January 2020 - - French pharmaceutical company Ipsen (Euronext: IPN) (OTC: IPSEY) has decided 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, as well as the ongoing Phase II (PVO-1A-202/204) extension studies, the company said.

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 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 (annualised change in new HO volume as compared with Natural History Studyi) 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 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.

Ipsen said it will collaborate and consult with the patients, investigators, ethics committees and regulatory authorities to define next steps for the programme, in the best interests of patients, whilst ensuring consent of all parties involved.

Ipsen is currently assessing the financial implications of these developments, including the financial outlook for 2022, and will present in February updated views together with Full Year 2019 results.

Palovarotene is a RARγ agonist being developed as a potential treatment for patients with ultra-rare and debilitating bone diseases, including fibrodysplasia ossificans progressiva and multiple osteochondromas, as well as other conditions including dry eye disease.

Palovarotene, which had rare pediatric disease and breakthrough therapy designations for the treatment of an ultra-rare bone disorder, was acquired by Ipsen through the acquisition in April 2019 of Clementia Pharmaceuticals.