Ipsen to Reinitiate Late-Stage Trial of Drug for Rare Bone Disease, Terminates Pediatric Study

Rare Daily Staff

Ipsen said it will reinitiate dosing of its experimental drug palovarotene in patients 14 years of age and older with fibrodysplasia ossificans progressiva, a rare bone disease.

The company said the U.S. Food and Drug Administration has confirmed they have no safety concerns with restarting dosing in patients 14 years of age and older. Ipsen said it has received clearance to reinitiate dosing from regulatory authorities in Europe, Canada, and Latin America.

Ipsen also said it will terminate its study of the drug in patients with multiple osteochondromas to analyze accumulated data and assess the future of palovarotene in this indication. The U.S. Food and Drug Administration placed a partial clinical hold in December for patients under the age of 14 to testing palovarotene in FOP and multiple osteochondroma. Ipsen said because of the duration of the partial hold there is now a significant gap in dosing, which may compromise the integrity of the data in that trial.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling disorder characterized by bone that forms outside the normal skeleton, in muscles, tendons or soft tissue. FOP is among the rarest diseases with approximately 1,000 confirmed cases globally. 

Palovarotene is a RARγ agonist being developed as a potential treatment for FOP and multiple osteochondromas (MO), as well as other conditions including dry eye disease. Ipsen gained ownership of palovarotene through its $1.3 billion acquisition of Clementia Pharmaceuticals in April 2019.

Ipsen paused dosing of palovarotene in late January in the global phase 3 MOVE trial, as well as the ongoing phase 2 extension studies in FOP based on results of a futility analysis as part of the pre-specified interim analysis. But it said encouraging therapeutic activity was observed in preliminary post-hoc analyses of interim data for the phase 3 MOVE trial and shared it with, and was acknowledged by the Independent Data Monitoring Committee.

The company subsequently amended the protocol for the phase 3 MOVE trial to include updates to the statistical analysis section as recommended by the IDMC to allow for additional analyses to be performed in addition to the primary pre-specified analysis. The protocol amendments are based on the IDMC’s observation that the protocol pre-specified statistical model may have negatively affected the efficacy analysis and shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment.

“After consultation with patient groups and investigators, we have been working diligently with all relevant stakeholders to restart the trial as quickly as possible,” said Howard Mayer, executive vice president and head of research and development at Ipsen. “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.”

Ipsen is now working to obtain the approvals from the ethics committee of each clinical site and, upon receipt of both regulatory approval where required and European Commission approval, the re-initiation of dosing may begin. The company said appropriate measures will also be taken to ensure the safety of FOP patients who restart dosing in light of the ongoing COVID-19 pandemic, taking into consideration local regulatory and health authority guidance, as well as the ability of individual investigators and sites to adequately monitor patient safety.

Photo: Howard Mayer, executive vice president and head of research and development at Ipsen