Ipsen Voluntarily Withdraws FDA Submission for FOP Drug
After discussions with the U.S. Food and Drug Administration (FDA), Paris-based Ipsen withdrew its New Drug Application (NDA) for palovarotene. The drug is being developed for the prevention of heterotropic ossification, which is new bone formation in people with fibrodysplasia ossificans progressive (FOP).
FOP is an ultra-rare genetic disease marked by new bone formation outside the normal skeletal system, such as soft connective tissues. This process is called heterotopic ossification (HO). It affects about 1.36 people per million around the world.
Palovarotene is an oral, selective retinoic-acid receptor gamma agonist. It has received rare pediatric disease and breakthrough therapy designations from the FDA for FOP. Ipsen acquired the drug when it bought Clementia Pharmaceuticals in April 2019.
After meeting with the FDA about its acceptance of the NDA under Priority Review, they decided that more data analysis would be needed, and the agency couldn’t complete it within the current NDA review schedule. So Ipsen withdrew the NDA and expects to resubmit it once the continued analysis is finished.
“We remain committed to the FOP community through our clinical programs for Ipsen’s two investigational therapies, palovarotene and IPN60130,” said Howard Mayer, executive vice president and Head of Research and Development, Ipsen. “We recognize the urgency from this community to bring a much-needed treatment option to people living with FOP around the world. Unfortunately, as there is no regulatory mechanism to ‘pause’ the current ongoing review process, we have taken the decision to withdraw the NDA for palovarotene to undertake the additional analyses and evaluation needed, with plans to resubmit the data for palovarotene as soon as possible.”
The drug is still being evaluated in the Phase III MOVE trial, an open-label, single-arm study of the efficacy and safety of a chronic/flare-up administration regimen of palovarotene. In the study, patients are given a 5mg daily dose that is increased at the beginning of a flare-up to 20mg for four weeks, then 10mg for eight weeks. At the end of the flare-up period, the dosing is dropped to the chronic 5mg daily dose. Doses are adjusted based on the weight in “skeletally immature participants” in people 18 years of age or younger.
The clinical trial is being run in Argentina, Australia, Brazil, Canada, France, Italy, Japan, Spain, Sweden, the UK, and the U.S. There are also two ongoing Phase II extension trials in France.
A partial clinical hold was announced in December 2019 to patients under 14 who were in the Phase II PVO-1A-202/204 and PVO-2A-201 trials and the Phase III PVO-1A-301 study. Based on a futility analysis, they then paused the Phase III MOVE trial and the Phase III extension studies on January 24, 2020.
The analysis demonstrated encouraging therapeutic activity, and they amended the protocol for the Phase III MOVE trial. The Independent Data Monitoring Committee (IDMC) noted 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.” In March 2020, the studies resumed in patients 14 years or older across all the programs.