The company hopes to resume the trials following an assessment of data.
Ipsen has decided to temporarily pause dosing in its studies of palovarotene trials for patients with fibrodysplasia ossificans progressiva following a recommendation from an Independent Data Monitoring Committee. The company hopes to resume the trials following an assessment of data.
The France-based company said that in both the Phase III and Phase II extension studies, the IDMC recommended suspending he trials following a futility analysis that showed the Phase III study was unlikely to meet its primary efficacy endpoint of annualized change in new HO volume as compared with Natural History Study.
The company did have some positive news to report, though. Despite the results of the pre-specified interim analysis, Ipsen said it observed “signals of encouraging therapeutic activity” in preliminary post-hoc analyses of the Phase III trial. That information was shared with the IDMC which, as a result, is recommending not to discontinue the study. In its recommendations, the IDMC notes highly disparate results precluding a confident conclusion about futility, Ipsen said in its announcement this morning. Additionally, Ipsen said the IDMC also noted that the protocol-pre-specified model may have negatively affected the efficacy analysis and shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment.
Ipsen said it will pause the dosing of the patients in the Phase II and Phase III trials and conduct additional assessments of the complete data set. Based on the IDMC’s observations and recommendations, Ipsen will discuss these findings with regulatory authorities to determine the path forward for the palovarotene program in FOP, the company said.
“While the study has met pre-specified statistical futility, we are encouraged by the results observed in the preliminary post-hoc analyses and look forward to discussing these with regulators as quickly as possible to determine the next steps for the palovarotene program,” Aymeric Le Chatelier, Ipsen’s chief executive officer said in a statement. “We gratefully acknowledge the ongoing support and trust from patients, their families and the healthcare professionals involved in these trials. We are deeply committed to drug development in the area of rare and ultra-rare diseases where there are multiple high unmet medical needs and often a limited understanding of the disease itself.”
Ipsen gained palovarotene last year following the acquisition of Canada-based Clementia for $1.3 billion. Palovarotene inhibits excess bone morphogenetic protein (BMP) signaling which is linked to the progression of FOP and MO, both of which are rare disabling bone disorders for which there are no currently approved treatments.
While the Phase III trial will likely resume under new protocols, Ipsen noted that a partial clinical hold for the pediatric population under the age of 14 for FOP and multiple osteochondromas placed by the U.S. Food and Drug Administration last month remains in effect. In December, the FDA issued the partial clinical hold following safety reports that raised concern about early growth plate closure in pediatric patients with FOP treated with palovarotene.
Ipsen said it is assessing the financial implications of the new trial developments, including the financial outlook for 2022, and will present updated views along with 2019 financial results in February.
