Ipsen's rare disease drug palovarotene knocked back in EU

Ipsen has suffered a setback in its marathon effort to bring palovarotene to market for ultra rare disease fibrodysplasia ossificans progressiva (FOP), after EU advisors recommended against approval.

The EMA's human medicines committee delivered a negative opinion on palovarotene, making it very unlikely that the drug will be approved by the European Commission, although Ipsen says it will be requesting a re-examination of the marketing application.

The decision comes after Ipsen was forced to withdraw its marketing application for palovarotene in the US in 2021, which delayed regulatory filings elsewhere, although the French pharma company has picked up an approval for the drug in Canada, where it is sold as Sohonos.

It refiled in the US, but got a complete response from the FDA in December with a request for more clinical information that has delayed the programme even further, and the CHMP's decision will further undermine confidence in the drug's prospects.

Palovarotene was acquired by Ipsen as part of its $1 billion upfront acquisition of Clementia Pharma in 2019, but almost immediately ran into trouble. It failed a futility test in a pivotal trial and was also placed under a partial clinical hold by the FDA in 2020 while a safety signal was investigated.

At the moment, the only therapy available to patients with FOP – a disorder in which bony lesions are laid down in muscles, tendons, and ligaments – are drugs to treat symptoms including pain.

Palovarotene would be the first treatment that aims to reduce the formation of extra-skeletal bone deposits, striking at the mechanism underlying FOP, which has only been diagnosed in around 900 people worldwide.

"We continue to work closely with the EMA to address the outstanding concerns that led to the decision today, with the goal of making this investigational medicine available to appropriate patients living with this debilitating disease," said Ipsen's head of R&D, Howard Mayer, in a statement.

"Ipsen remains committed to bringing new therapeutic options to the FOP community, which has been instrumental in the development of investigational palovarotene through their involvement in clinical trials," he added.

Even if Ipsen can eventually get palovarotene over the line in the EU and US, any lead it may have enjoyed over rival FOP therapy developers is being winnowed away. Those include Regeneron, whose garetosmab candidate has experienced its own problems, including an FDA clinical hold, but has now progressed into phase 3 testing.

Ipsen, meanwhile, also has another FOP candidate in its portfolio via its $535 million agreement with Blueprint in 2019 for BLU-782, an ALK2 inhibitor.