Ipsen's Class 1 New Drug Palovarotene Capsules Receive IND Approval in China for Rare Genetic Disorder FOP

By | Pharma Insights

On August 19, the latest public notice from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) revealed that Ipsen’s Class 1 new drug, palovarotene capsules, has been granted implied approval for clinical trials. The drug is intended to be developed for a very rare genetic disease. Palovarotene is a selective RARγ inhibitor acquired by Ipsen through its purchase of Clementia Pharmaceuticals for over $1.3 billion. In the United States, the FDA has accepted the New Drug Application (NDA) for palovarotene and granted it Priority Review designation, with a regulatory decision expected by November 30 this year.

Screenshot source: CDE official website

Palovarotene is a novel, selective retinoic acid receptor gamma (RARγ) agonist being developed for the treatment of fibrodysplasia ossificans progressiva (FOP), multiple osteochondromas (MO), dry eye disease, and other conditions. Previously, palovarotene has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of FOP and MO, as well as Fast Track designation and Breakthrough Therapy designation from the FDA.

Palovarotene was the lead candidate drug of Clementia Pharmaceuticals, a rare disease drug development company. In February 2019, Ipsen and the company jointly announced that they had signed an acquisition agreement, whereby Ipsen would acquire the latter for a total transaction value of up to $1.31 billion. Since then, Ipsen has held the development rights to palovarotene.

Palovarotene capsules have been approved for clinical trials in China. The proposed indication for development is: for the prevention of heterotopic ossification in adult and pediatric patients with FOP (progressive ossifying myositis). FOP is a very rare genetic disorder caused by mutations in the ACVR1 (also known as ALK2) gene. The ACVR1 protein belongs to the bone morphogenetic protein (BMP) type I receptor family, which regulates the growth and development of bone and muscle.

Another common name for FOP is "Stone Man Syndrome," which refers to the fact that as the disease progresses, patients become as immobile as stone. The primary manifestation of this rare disease is that the body's normally soft and elastic muscles and connective tissues become inflamed following minor injuries and subsequently transform into bone. Due to the absence of approved therapies for this progressive and debilitating condition, a significant unmet medical need remains within the FOP patient population.

The advent of palovarotene is expected to transform the current treatment landscape. According to data from the MOVE clinical trial, a post-hoc analysis of the primary endpoint revealed that, compared with untreated patients in natural history studies, patients treated with palovarotene exhibited a 62% reduction in the mean annual volume of new heterotopic ossification (p=0.0292).

According to a press release previously issued by Ipsen, this also marks the first global multicenter Phase 3 clinical trial for FOP. Based on data from the MOVE trial, a New Drug Application (NDA) for palovarotene has been submitted to the FDA. If approved, palovarotene would become the world’s first therapy for FOP.

Notably, in the field of FOP treatment, Ipsen has also introduced another candidate product, BLU-782. It is a highly selective oral ALK2 inhibitor. In October 2019, Ipsen, through its subsidiary, entered into a collaboration with Blueprint Medicines valued at over $500 million, thereby securing the development rights for BLU-782.

We look forward to both palovarotene and BLU-782 advancing smoothly through clinical trials and soon providing new treatment options for patients with FOP.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration. Retrieved Aug 19, 2021, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=25#

[2] Ipsen to Acquire Clementia Pharmaceuticals to Significantly Boost Rare Disease Portfolio Retrieved on February 25 2019 from https://www.ipsen.com/press-releases/ipsen-to-acquire-clementia-pharmaceuticals-to-significantly-boost-rare-disease-portfolio/

[3] Ipsen Confirms U.S. FDA Accepts New Drug Application for Palovarotene as the First Potential Treatment Worldwide for Fibrodysplasia Ossificans Progressiva (FOP). Retrieved May 31, 2021, from https://www.businesswire.com/news/home/20210528005422/en

[4] Ipsen and Blueprint Medicines Announce Exclusive Global License Agreement to Develop and Commercialize BLU-782 for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP), Retrieved October 16, 2019, from https://www.businesswire.com/news/home/20191015006093/en

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