First Therapy Approved for Ultra-Rare Bone Disorder

The FDA approved the oral retinoid palovarotene (Sohonos) for treating abnormal bone growth associated with fibrodysplasia ossificans progressiva (FOP), drugmaker Ipsen announced on Wednesday.

Palovarotene, a selective retinoic acid receptor gamma agonist, is indicated for reducing the volume of new heterotopic ossification in adults and children: boys ages 10 years and up and girls ages 8 and up.

FOP is an ultra-rare, progressive disease that affects an estimated 400 people in the U.S., according to the company. It is characterized by episodes of rapid bone growth that can seriously impede patients' mobility and daily function, including their ability to eat, drink, or use the restroom independently.

Most patients need a wheelchair by the age of 30, and the disease can significantly shorten lives -- bone growth around the rib cage can result in breathing problems and cardiorespiratory failure.

"As a clinician caring for patients with FOP, I personally see the daily challenges and stresses that our patients and their families must contend with," Edward Hsiao, MD, PhD, of the University of California San Francisco, said in a statement.

Approval of palovarotene was based on findings from the single-arm, open-label phase III MOVE study, which included 107 adult and pediatric patients with FOP. Treatment with the retinoid reduced annualized heterotopic ossification volume compared with a natural history study, where patients received standard care but without the drug.

"The published phase III MOVE study showed that Sohonos can decrease new heterotopic ossification, and that palovarotene can be tolerated by many patients with FOP," said Hsiao, an investigator on the study.

But the drug is not for everyone, he cautioned.

"As with all medicines there are risks, in this case especially for young children who may develop early growth plate closure," he said. "In addition, Sohonos has the same side effects as other retinoids, including dryness of the skin and mucus membranes. However, since the accumulation of [heterotopic ossification] in FOP is progressive, irreversible, and life altering, this medication is an important treatment option for our FOP community."

While there were data issues with the trial, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee largely agreed earlier this year that palovarotene's benefits outweighed its risks for patients with this debilitating condition.

The most common adverse events in MOVE included dry skin, lip dryness, alopecia, drug eruption, rash, pruritus, arthralgia, and premature growth plate closure in children.

In the FDA's announcement, the agency recommended that pediatric patients be monitored for linear growth due to the risk for premature growth plate closure.

"Before taking Sohonos, all growing pediatric patients should undergo skeletal maturity baseline assessments. Continued monitoring is recommended every 6 to 12 months until patients reach skeletal maturity or final adult height," the FDA said.

Palovarotene is contraindicated in pregnant patients and people with a known allergy to retinoids. Prescribing information for the drug also includes warnings and precautions related to the premature epiphyseal closure in growing pediatric patients, mucocutaneous side effects, metabolic bone disorders, psychiatric disorders, and night blindness. Given the risk of metabolic bone disorders, patients should periodically be radiologically assessed for spinal fractures, according to the FDA.

The drug can be prescribed immediately to eligible patients, Ipsen said. Palovarotene's recommended dosing is 5 mg daily for adults and kids 14 and older (or the weight-based equivalent for younger patients). The dose can also be modified to deal with flare-up symptoms.

Comment