Ipsen Confirms U.S. FDA Accepts New Drug Application for Palovarotene as the First Potential Treatment Worldwide for Fibrodysplasia Ossificans Progressiva (FOP)
Ipsen (ADR: IPSEY) announced the FDA's acceptance of its New Drug Application (NDA) for palovarotene, an investigational treatment for fibrodysplasia ossificans progressiva (FOP). The NDA is based on the MOVE trial, showing a 62% reduction in new HO volume in treated patients. FOP is an ultra-rare genetic disorder affecting 1.36 per million individuals, causing debilitating new bone formation. The FDA's target action date is November 30, 2021. Ipsen aims to address the unmet medical needs of FOP patients and plans further global regulatory submissions.
- FDA acceptance of NDA for palovarotene is a significant milestone.
- MOVE trial shows a 62% reduction in new HO volume, indicating potential treatment efficacy.
- Palovarotene addresses an unmet medical need for FOP, an ultra-rare genetic disorder.
- 29.3% of participants in MOVE trial reported at least one serious adverse event.
- Treatment-related adverse events included 97% skin and subcutaneous disorders.
Regulatory News:
Ipsen (Euronext: IPN; ADR: IPSEY) today 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.1,2 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”.2 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.3
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
“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.
ENDS
About the palovarotene FOP clinical program
The Phase III MOVE (NCT03312634) 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
In December 2019, a partial clinical hold was applied to participants under the age of 14 years participating in the Phase II (PVO-1A-202/204 and PVO-2A-201) and Phase III (PVO-1A-301) studies at all clinical sites globally. This was due to reports of premature physeal closure (PPC). A decision to pause dosing of palovarotene in all remaining participants in the global Phase III MOVE trial (PVO-1A-301), as well as the ongoing Phase II (PVO-1A-202/204) extension studies in FOP was made by Ipsen on January 24, 2020, based on results of a futility analysis as part of the pre-specified interim analysis (Bayesian compound Poisson analysis with square root transformation of the new HO volume data).
*Encouraging therapeutic activity was observed in post hoc analyses of interim data for the Phase III MOVE trial and shared with, and acknowledged by, the Independent Data Monitoring Committee (IDMC). Post hoc analyses included Bayesian compound Poisson analysis without square-root transformation, and weighted linear mixed-effects models (with/without square-root transformation of the new HO volume data). As such, the Company amended the protocol for the Phase III MOVE trial to include updates to the statistical-analysis section, including additional analyses requested by the IDMC, to be performed in addition to the primary pre-specified analysis. The protocol amendments are based on the IDMC’s observation that the protocol pre-specified statistical model may have negatively affected the efficacy analysis and appears to have shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment. Dosing for eligible study patients ≥14 years of age has resumed as of March 26, 2020 across the Phase II and Phase III programs for palovarotene in FOP.
About palovarotene
Palovarotene is an oral investigational, selective retinoic-acid receptor gamma (RARγ) agonist being developed as a potential treatment for people living with the debilitating ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). Palovarotene, which received rare pediatric disease and breakthrough therapy designations from the FDA for the potential treatment of FOP, was acquired by Ipsen through the acquisition of Clementia Pharmaceuticals in April 2019.
About fibrodysplasia ossificans progressiva (FOP)
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by bone that forms outside the normal skeleton, in muscles, tendons, or soft tissue.3 FOP has an estimated prevalence of 1.36 per million individuals; however, the number of confirmed cases varies by country.1,2
About Ipsen
Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and Specialty Care. The Group develops and commercializes
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