Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic condition due to which bones form outside the exoskeleton. This condition is called heterotopic ossification (HO).
Palovarotene capsules are selective retinoic-acid receptor gamma (RARγ) agonists that Ipsen has developed for the treatment of this disease and while they have been approved in Canada for the treatment of adults, girls over the age of 8 years and boys over 10 who are suffering from HO, the drug is yet to gain approval in the U.S.
In the U.S. the company is also seeking approval for similar use.
When Ipsen initially submitted its drug to the FDA in 2021, it had been accepted for priority review, however, 3 months later the company withdrew the application on the grounds that the additional analysis and evaluative data required from the Phase 3 MOVE trial and FOP program could not be produced within the time frame of the review cycle, thus, the NDA review was halted.
Toward the end of June however, FDA accepted Ispen’s priority NDA review application once again and the company has predicted December end as the target action time. There was no explicit outline of what data was included in this resubmission but during the company’s first attempt to gain approval, it used data from the post-hoc analysis of the phase 3 MOVE trial.
This data showed a 62% reduction in the average annual new heterotopic ossification volume of patients who took the medication compared to those who did not receive treatment.
The company has clarified that none of the data that is requested pertains to the safety profile of the drug and that they are working to fulfill the agency’s request as quickly as possible.
Ipsen further explained,” We will work expediently with the FDA as we remain committed to bringing innovative treatment options to the fibrodysplasia ossificans progressiva community,”
Apart from these current hurdles, the company also faced setbacks in 2019 when pediatric patients in trial testing for the medication showed cases of early growth plate closure. As a result, testing was put on hold for around 4 months. Previously the trial was also testing medication on patient populations that suffered from multiple osteochondromas but after this, the company had to remove this factor from the trial.
In addition to this, the company had to pause dosing in its phase 3 FOP trial, based on interim data predicting that it would be unlikely for the trial to meet its primary endpoint. This happened only a month after the holds were announced. Despite these challenges on the recommendation of its independent review board, the company did not discontinue the study.
Ipsen gained control of Palovarotene after it acquired it in its 2019 takeover of Clementia Pharmaceuticals. This takeover cost the company $1.31 billion.