- New Drug Application granted Priority Review status, with a decision anticipated on 30 November 2021
- European Medicines Agency (EMA) and Swissmedic have also validated the Marketing Authorization Application (MAA) for palovarotene with Swissmedic granting palovarotene a priority review
Ipsen announced that its New Drug Application (NDA) for palovarotene, an oral, investigational, selective RARγ agonist for the prevention of heterotopic ossification (new bone formation) as a potential treatment option for people living with the progressive disabling and ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP), has been accepted by the U.S. Food and Drug Administration (FDA). The target regulatory action date assigned by the FDA under a Priority Review status is 30 November 2021.
FOP is an ultra-rare genetic disorder with an estimated prevalence of 1.36 per million individuals; however, the number of confirmed cases varies by country. It is characterized by new bone formation outside of the normal skeletal system, like in soft connective tissues, a process known as heterotopic ossification (HO),3 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.
Dr. Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen, said “With no approved treatments for this progressive and debilitating disease, there remains a great unmet medical need for the FOP community. This year marks 15 years since the discovery of the mutation in the gene ALK2/ACVR1 which causes FOP, and the palovarotene submission is the first worldwide for a potential treatment in this disease. Our teams at Ipsen are now focused on working closely with regulatory authorities to bring this potential treatment option to people living with FOP around the world. We want to thank all the people living with FOP, their families, caregivers and healthcare teams who have participated in the palovarotene clinical program.”
The NDA for palovarotene is primarily based on data from the ongoing MOVE trial, the first global multi-center Phase III trial in FOP. MOVE is an open-label, single-arm trial, evaluating the efficacy and safety of a chronic/flare-up dosing regimen of palovarotene in decreasing new annualized HO volume in patients with FOP. Post hoc analyses* of the primary endpoint from the trial demonstrated a 62% reduction in mean annualized new HO volume in participants treated with palovarotene (8,821 mm3) (n=97) versus untreated participants from a natural-history study (23,318 mm3) (n=98) (nominal weighted linear mixed effects [wLME] model est. –11,611mm3, p-value = 0.0292). Overall, 29.3% of participants reported at least one serious adverse event (AE), including premature physeal closure (PPC) or epiphyseal disorder in 27.1% of the participants who were skeletally immature at baseline.4 As of the data cut-off, the most common treatment related AEs included skin and subcutaneous tissue disorders (97%), gastrointestinal disorders (77.8%), and infections and infestations (74.7%).4
“This FDA filing acceptance marks a significant milestone for Ipsen and those living with this relentless condition of FOP, which we hope will have a significant impact,” said Robert J. Pignolo, M.D., Ph.D., Chair, Geriatric Medicine & Gerontology, Mayo Clinic College of Medicine. “News of this potential new treatment will be welcomed by the FOP community, and we await further updates from the FDA. With ultra-rare conditions by their nature affecting very few people around the world it is so important we continue to make progress and advance the management of diseases like FOP.”
In addition to the European Medicines Agency (EMA) and Swissmedic MAA validations, Ipsen anticipates additional applications to other regulatory agencies in due course.