The wait for a new therapy to treat fibrodysplasia ossificans progressiva (FOP) just got longer. Ipsen announced they have withdrawn their New Drug Application (NDA) with the Food and Drug Administration (FDA) for the orphan drug palovarotene to treat FOP.
FOP is an ultra-rare genetic disorder characterized by new bone formation outside of the normal skeletal system, like in soft connective tissues, a process known as heterotopic ossification (HO), which can be preceded by painful soft-tissue swelling or “flare-ups”. Flare-up episodes are common and are a substantial contributor to the formation of new HO, however HO can form in the absence of a flare-up. HO, once formed, is irreversible and leads to loss of mobility and shortened life expectancy.
Palocarotene is an investigational, oral, selective RARγ agonist for the prevention of HO as a potential treatment for people living with FOP.
The FDA accepted the NDA for palovarotene in May 2021. However, during review and continued dialogue between Ipsen and the FDA, it was agreed that additionally analyses and evaluation of data collected from Ipsen’s phase 3 MOVE and phase 2 extension studies (Study 202 [NCT02279095] and Study 204 [NCT02979769]) would be required to progress and complete the review process. As analysis and evaluation of either of these programs would be impossible to complete within the current NDA review cycle, Ipsen confirmed their withdrawal of the NDA for palovarotene. According to Ipsen, they plan to resubmit to the FDA upon completion of the additional data analyses.
The phase 3 MOVE trial is an ongoing open-label, single-arm trial evaluating the efficacy and safety of a chronic/flare-up dosing regimen of palovarotene, which comprises a 5mg daily dose that is increased at the start of a flare-up to 20mg for four weeks, followed by 10mg for eight weeks. At the end of the flare-up dosing period, the dose returns to the chronic 5mg daily dose. All dosing is weight-adjusted in skeletally immature participants (those under the age of 18 years with less than 90% skeletal maturity on hand/wrist x-rays performed at screening). Study 202 is an open-label extension of Study 201, the initial Phase II randomized, double-blind, multi-center trial. Study 204 is an open-label trial to evaluate the safety and efficacy of different palovarotene dosing regimens in patients with FOP in France.
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