Ipsen's $1B bet on the ropes after interim phase 3 analysis

stop sign
Shares in Ipsen fell 24% following news of an interim analysis. (Dimitris Vetsikas/Pixabay)

Ipsen has paused a phase 3 trial of palovarotene after an interim analysis found it is unlikely to meet its primary efficacy endpoint. The setback is another blow for the retinoic acid receptor gamma agonist, which has run into safety and efficacy problems since Ipsen acquired it in a $1.3 billion (€1.1 billion) takeover of Clementia Pharmaceuticals.

David Meek, then the CEO of Ipsen, called experimental fibrodysplasia ossificans progressiva (FOP) drug palovarotene “largely derisked” when he unveiled the deal to acquire Clementia last year. Since then, palovarotene has been the subject of a safety signal that led the FDA to stop dosing in kids, a key population, and has now been rocked by an analysis that calls its efficacy into question.

After performing an interim review of data from a phase 3 trial, the independent data monitoring committee (IDMC) found the pivotal study is unlikely to meet its primary efficacy endpoint. The endpoint is comparing the change in new heterotopic ossification volume to results from a natural history study.


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Ipsen responded to the analysis by pausing dosing in the phase 3 and its phase 2 extension studies. However, Ipsen is yet to give up on the studies or on palovarotene.

According to Ipsen, the IDMC did not recommend discontinuing the phase 3 as there are “highly disparate results” that prevent “a confident conclusion about futility.” The IDMC reportedly noted that the “protocol-prespecified model may have negatively affected the efficacy analysis and shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment.”

Ipsen will try to figure out what is going on while dosing in the studies is paused. That will entail talking to regulators about the data with a view toward deciding the next steps for the program.

However, while it is possible dosing will resume, expectations that Ipsen will recoup its outlay on Clementia are falling fast. The safety signal and subsequent partial clinical hold dealt the first blow to the prospects of palovarotene. The interim analysis has delivered another hit. 

“Another setback for palovarotene is likely to weigh on the shares, with trials now paused after the phase 3 MOVE study failed a pre-specified futility analysis as a treatment for rare bone disorder FOP, casting further doubt on its future. Expectations were already low after the recent safety-related FDA partial clinical hold, but this is a further blow to sentiment,” analysts at Jefferies wrote in a note to investors.

The back-to-back setbacks leave Ipsen’s big push to diversify its portfolio in tatters less than a year after it unveiled the Clementia takeover. If palovarotene fails, Ipsen’s deal for Blueprint Medicines' ALK2 inhibitor BLU-782 will leave it with a fallback option in FOP.

Shares in Ipsen fell 24% following news of the interim analysis. 

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