Ipsen's rare disease candidate rejected after mounting setbacks, delays

Ipsen’s “largely derisked” rare disease candidate was evidently still too risky for regulators, with the FDA rejecting the company’s new drug application for palovarotene.

The decision by regulators, announced by the company late Friday night, comes two months after the FDA delayed an advisory panel meeting to discuss palovarotene and the agency's request for additional data. Ipsen said the complete response letter is related to that previous request, and it intends to respond by the first quarter of 2023, triggering a new six-month review cycle. The company also said the FDA has not yet rescheduled the advisory meeting. 

Ipsen has not specified what kind of data regulators have been asking for, saying only that it’s not a request for additional efficacy or safety data beyond existing studies. A spokesperson for the company declined to comment when asked which data it's working to provide. Such secrecy naturally leaves open a plethora of possibilities regarding the data request, including the drug's development and manufacturing. Palovarotene is being developed as a treatment for fibrodysplasia ossificans progressiva (FOP), an ultra-rare bone growth disorder marked by the development of bones in parts of the body where they shouldn’t be. 

The news marks the latest and greatest setback for palovarotene, which has faced a persistent uphill climb since Ipsen acquired the drug in its $1.31 billion purchase of Clementia Pharmaceuticals in 2019. Then-Ipsen CEO David Meek called the med “largely derisked,” evidently jinxing its future development path, which has been treacherous ever since. 

Before 2019 concluded, palovarotene was slapped with a clinical hold in studies evaluating the med in pediatric populations with FOP and multiple osteochondromas after evidence of cases of early growth plate closure. The company ultimately diverted all efforts toward FOP, with the hold lifted four months later. But before that happened, the company paused dosing in a phase 3 FOP trial that included adults after early evidence suggested the trial would not meet its primary endpoint. 

But that did not deter Ipsen from haggling with U.S. regulators about its therapeutic potential, particularly for a population that had no options. The company pulled its first NDA application in August 2021 to add more data, and the FDA accepted its resubmitted file in June 2022. While the company hashed out its approval package in the U.S., the drug was approved in Canada in January. 

Buoying Ipsen’s prospects, as bleak as they seem, has been the market potential should the company expand on its green light in Canada. Competitor BioCryst axed development of its FOP candidate in November, leaving Ipsen and Regeneron as the two major players in the space. Should Ipsen meet its first-quarter timeline for answering the FDA’s questions, it would still be on pace for a definitive answer from the FDA before Regeneron is expected to submit an approval application for its candidate in 2024.

Editor's note: This story was updated to include a response from an Ipsen spokesperson.