Ipsen craters as pricey rare disease drug is put on hold again

French drugmaker Ipsen’s big-ticket investment in rare bone disease drug palovarotene is looking increasingly like a poor deal, as the programme suffers another setback.

The drug – acquired by Ipsen under the tenure of its former chief executive David Meek as part of its $1 billion upfront acquisition of Clementia Pharma just under a year ago – has failed a futility test in its pivotal trial and dosing is being halted.

The prospects for palovarotene had already been dented by the FDA’s decision to place the drug on a clinical hold on safety concerns late last month.

The programme is on pause in both a phase 3 trial in fibrodysplasia ossificans progressiva (FOP), as well as phase 2 follow-up studies in the same indication. That makes any chance of sticking to its plans for a swift 2020 launch in FOP look vanishingly slim, although Ipsen isn’t abandoning the project just yet.

Palovarotene is a retinoic acid receptor gamma selective agonist and one of the top pipeline projects for FOP, a life-shortening disorder in which tendons and ligaments gradually become more bone-like, impairing movement as well as difficulty opening the mouth, impairing eating and speaking, and preventing normal breathing.

When it bought Clementia, Ipsen said it also planned to test palovarotene in multiple osteochondromas (MO) and other diseases.

In a statement, Ipsen said that there were “highly disparate results” in the trial which made it impossible to draw a “confident conclusion about futility.” It also suggested that the statistical design of the trial may have skewed the results towards a lack of benefit, adding it will look into the data further while the studies are on hold, whilst also discussing the findings with regulators.

The pause on testing – coupled with the earlier FDA decision to place a hold on testing the drug in children aged under 14 due to concerns of bone overgrowth – weighed heavily on the company’s share price, which fell almost a quarter after the announcement

Aymeric Le Chatelier, who took over from Meek after the latter moved to head gene therapy start-up FerGene shortly after the clinical hold was announced, said: “we are encouraged by the results observed in the preliminary post-hoc analyses.”

If palovarotene does end up being a dud there are some other clinical candidates coming through the pipeline, including an antibody-based drug from Regeneron – garetosmab – that showed positive phase 2 results a couple of weeks ago.

Ipsen meanwhile also has another FOP candidate in its portfolio via its $535 million agreement with Blueprint last October for BLU-782, an ALK2 inhibitor. FOP is caused by a mutation in the gene for ALK2, which is known as ACVR1.

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