European Commission rejects Ipsen’s ultra-rare disease drug after two negative opinions from EMA

The European Commission has rejected Ipsen’s potential new drug palovarotene for those with the ultra-rare genetic connective tissue disorder known as fibrodysplasia ossificans progressiva, or FOP.

The decision follows two negative opinions from the European Medicines Agency in January and May. And whereas the US FDA recently said it might be open to a post-hoc analysis of a failed late-stage trial for palovarotene, the EMA said in May:

At the time of the initial evaluation, the Agency considered that no firm conclusions could be drawn on the benefits of the medicine, as the applicant’s conclusion was based on a post-hoc analysis which was neither scientifically nor clinically justified and pre-specified study objectives were not met.

Howard Mayer

“We believe that our clinical data provide evidence supporting the effect of palovarotene on the reduction of new, abnormal bone formation, known as heterotopic ossification, which characterizes the disease. We are therefore disappointed that the European Commission decided not to approve this treatment for patients with FOP in Europe,” Ipsen EVP Howard Mayer said in a statement.

The FDA, meanwhile, said it might be willing to support a post-hoc analysis in the case of palovarotene even as post-hoc analyses are generally considered hypothesis-generating and can lead to inflating the type-I error and adding bias toward a favorable outcome.

“However, in this specific context, FDA acknowledges that the prespecified primary analysis may not have been the appropriate method for analyzing the primary endpoint for the reasons outlined below. Acknowledging the limitations of the prespecified analyses, we think it is reasonable to consider alternative more appropriate analyses to assess evidence of efficacy,” the agency said ahead of an adcomm meeting on June 28.

The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee then voted in favor of the drug’s approval, concluding 10-4 that evidence from a Phase III study showed the drug was effective, and 11-3 that the benefits of the drug outweighed its risks.

Last December, however, the FDA rejected the drug, asking for more data. Ipsen resubmitted the drug, and hopes to win approval in adults and children: females aged 8 years and older and males 10 years and older with progressive disease. The PDUFA date is set for Aug. 16.

fda