Ipsen has paused the dosing of patients in Phase II extension and Phase III clinical studies of palovarotene for the treatment of fibrodysplasia ossificans progressiva (FOP).
Palovarotene is a retinoic acid receptor γ (RARγ) agonist intended to address rare and debilitating bone diseases, such as FOP and multiple osteochondromas (MO).
Ipsen gained the drug during the acquisition of Clementia Pharmaceuticals in April last year.
The Phase II PVO-1A-202/204 extension and Phase III PVO-1A-301 studies involved chronic and episodic dosing of the drug. In these studies, dosing was paused based on interim analysis data.
A futility analysis by the Independent Data Monitoring Committee (IDMC) found that the Phase III trial may not achieve the primary efficacy endpoint of annualised change in new HO volume.
However, preliminary post-hoc analyses of the Phase III trial indicated encouraging therapeutic activity and this data was shared with the IDMC. As a result, IDMC recommended the study continue.
The committee noted the possibility of a negative effect of the protocol-pre-specified model on the efficacy analysis.
The company will pause dosing in the trials and further analyse the complete data set. It will discuss the findings with regulators to decide the path forward for the palovarotene FOP programme.
In addition, the company is analysing the financial effects of these developments.
Ipsen CEO Aymeric Le Chatelier said: “While the study has met prespecified statistical futility, we are encouraged by the results observed in the preliminary post-hoc analyses and look forward to discussing these with regulators as quickly as possible to determine the next steps for the palovarotene programme.”
The partial clinical hold placed last month on paediatric patients at all global sites of the Phase II PVO-1A-202/204, PVO-2A-201, and Phase III PVO-1A-301 trials assessing palovarotene is still in effect.
