In 2022, the U.S. Food and Drug Administration (FDA) examined the potential of approving palovarotene, a selective RARγ agonist, for the treatment of fibrodysplasia ossificans progressiva (FOP). However, the FDA did not feel that it had enough information on the drug for approval. While the FDA requested additional data on the drug in October 2022, it later rejected the New Drug Application (NDA) and issued a Complete Response Letter (CRL) in December 2022. The European Medicines Agency (EMA) also recommended against the approval of palovarotene in the European Union.

But reporting from Fierce Biotech suggests that Ipsen is not giving up yet – in either location. The company is calling for the EMA to re-examine its position on the drug. To the FDA, Ipsen submitted a multitude of data relating to palovarotene, including data from the Phase 3 MOVE clinical trial. Altogether, 107 individuals enrolled. Findings from the study show that palovarotene reduced new abnormal bone formation (heterotopic ossification) by 60% compared to the current standards-of-care.

Despite this promising data, there have also been multiple obstacles on the journey to approval. For example, a Phase 3 clinical trial stopped dosing patients early-on after evidence failed to signify that the trial might meet its primary endpoint. In a pediatric study, cases of early growth plate closure prompted a partial clinical hold for 4 months. These instances have not stopped the drug’s approval in Canada, though it has clearly halted progression elsewhere.

It’s unclear what will come from the FDA’s renewed examination of palovarotene, but if the drug was approved, it would mark the first approved FOP treatment.

What to Know about Fibrodysplasia Ossificans Progressiva (FOP)

Fibrodysplasia ossificans progressiva is a rare genetic connective tissue disorder characterized by abnormal bone development outside of the skeletal structure. For example, ossification may occur in the tendons, muscles, or ligaments. This makes movement difficult or, in some cases, impossible. The most common cause of FOP is an ACVR1 mutation. Normally, this gene plays a role in promoting and regulating bone growth. Ossification may begin in the neck or shoulders before progressing to the limbs. Symptoms and characteristics of FOP may include:

• Malformed big toes and/or thumbs (at birth)
• Abnormally short fingers and toes
• Firm, tender swellings that develop on a certain areas of the body
• A low-grade fever prior to the development of the above swellings
• Generalized pain and stiffness
• Scoliosis or kyphosis (abnormal spinal curvature)
• Difficulty walking

The above is not an exhaustive or complete list of FOP characteristics. There is no cure for FOP, but doctors may still prescribe treatments to help with symptoms. Muscle relaxants and corticosteroids can help manage symptoms such as pain and inflammation.