French Pharmaceutical Company Pauses Studies on Treatment for Rare Bone Disease

Ipsen, a French pharmaceutical company based in Paris, announced it has paused studies conducted on a drug used to treat fibrodysplasia ossificans progressive (FOP).

One study was a global phase 3 trial, designed to evaluate the efficacy and safety of palovarotene, a drug the company acquired for $1 billion in April 2019. Ongoing phase 2 extension studies were also paused.

According to an Ipsen press release, “The decision to pause dosing patients in the trial is based on results of a futility analysis reviewed by the Independent Data Monitoring Committee (IDMC) as part of the prespecified interim analysis. The results of a futility analysis indicated that the Phase III FOP trial was unlikely to meet its primary efficacy endpoint…upon completion.”

In both studies, the drug was administered on a daily basis and on an as-needed basis. Palovarotene is a retinoic acid receptor gamma agonist that was being developed as a treatment for multiple osteochondromas (MO), dry eye disease, and other conditions in addition to FOP.

Aymeric Le Chateller, Ipsen’s chief executive officer, said of the announcement, “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.”

FOP occurs in about 1 in 1.6 million newborns and roughly 800 people worldwide are known to have the condition, according to the NIH. The disorder is “characterized by the gradual replacement of muscle tissue and connective tissue (such as tendons and ligaments) by bone, restricting movement…The formation of extra-skeletal bone causes progressive loss of mobility as the joints become affected.”

Although the trials have been paused, Ipsen notes the IDMC has not directed the company to discontinue the studies. “Signals of encouraging therapeutic activity were observed in preliminary post-hoc analyses of the Phase III trial and shared with and acknowledged by the IDMC,” the press release stated.

In December 2019, the FDA placed a clinical hold on use of palovarotene in children younger than 14 in Ipsen’s trials. “The FDA partial clinical hold for the pediatric population under the age of 14 for FOP and multiple osteochondromas (MO) issued on 4 December 2019, remains in effect,” the company said.

According to FierceBiotech, “FDA staff took the action in response to cases of early growth plate closure in children on the retinoic acid receptor gamma agonist.”