Ipsen Resumes Phase III Testing for Rare Disease Drug and Abandons Pediatric Trial

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The French pharmaceutical company Ipsen has restarted the dosing of its treatment for a rare bone disease in a phase III trial after obtaining questionable interim results. At the same time, the company has terminated a phase II trial of the same drug in pediatric patients with a different bone disorder following a partial clinical hold by the FDA.

Ipsen will restart the dosing in a phase III trial of its small molecule drug palovarotene in patients 14 years of age and older with fibrodysplasia ossificans progressive (FOP), an extremely rare and incurable disease characterized by abnormal bone growth.

Ipsen had paused dosing in January 2020 after a futility analysis raised doubts about the study’s chances of meeting its primary efficacy endpoint, which was to significantly reduce abnormal bone growth.

However, when further analysis revealed promising therapeutic activity for FOP after all, Ipsen updated the protocol to allow for new statistical analyses. The FDA and many regulators in Europe have given the move the go-ahead, and results are expected later this year.

“We remain committed to bringing palovarotene to patients living with this devastating disease and will continue our conversations with the health authorities to determine the most appropriate regulatory path forward,” said Ipsen’s R&D head, Howard Mayer, in a public statement. As of the time of publishing, Ipsen hasn’t responded to our request for further comments. 

Simultaneously, Ipsen plans to terminate a phase II trial of palovarotene in children with multiple osteochondromas (MO), a rare condition involving the bones growing benign tumors. 

This move follows a partial clinical hold issued by the FDA in December 2019, which raised concerns about early growth plate closure in pediatric patients given the drug. While Ipsen is now addressing the FDA’s safety questions, the company has a lack of optimism about the trial’s results after being halted for so long.

Specifically, the company outlined that the clinical hold created a significant gap in dosing, which may compromise data integrity; very few patients had reached the trial midpoint when the clinical hold began; and they didn’t have enough pediatric safety data to make a suitable risk analysis.

Palovarotene, which was acquired by Ipsen following its takeover of Clementia Pharmaceuticals in 2019, is a small molecule that inhibits the bone and cartilage overgrowth seen in FOP and MO by activating a protein called RARγ. 

The acquisition of palovarotene resulted in an unexpectedly rocky year for Ipsen. The clinical hold on pediatric dosing of palovarotene and the failed futility analysis in the phase III trial saw the company’s share price drop by around 35% within the space of a month. The departure of the then CEO David Meek right after the clinical hold was a further blow at the end of 2019. Despite optimism about Ipsen’s future, the prognosis for palovarotene is not what it once was – Ipsen recently reported a €669M drop in worth for the drug and has dramatically lowered its expectations about revenues forecast for 2022. 

Despite the bumpy times, Ipsen’s commitment to the FOP area seems undiminished. Last Autumn, Ipsen and US Blueprint Medicines Corporation entered a development and commercialization plan for an oral drug that specifically targets the protein mutated in FOP.

Elsewhere, the US giant Regeneron announced encouraging phase II results in adult FOP patients with its own candidate garetosmab, a human monoclonal antibody targeting activin A, a protein that drives abnormal bone formation in FOP. Pediatric trials for garetosmab are in the planning stage. 

Karen O’Hanlon Cohrt is a Science Writer and Editor with a PhD in biotechnology from Maynooth University, Ireland. She can be found on Twitter @KarenOHCohrt and you can check out her other work on her portfolio. 

Images from Shutterstock

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