FDA approves treatment for rare pediatric metabolic disorder

The FDA approved fosdenopterin injection, a first-in-class treatment to reduce risk for death due to molybdenum cofactor deficiency type A, a rare, genetic, metabolic disorder that typically presents in the first few days of life.

Patients with molybdenum cofactor deficiency type A experience severe and rapidly progressive neurologic damage including intractable seizures, feeding difficulties and muscle weakness from the accumulation of toxic sulfite metabolites in the central nervous system, according to an FDA press release. Most patients die in early childhood from infections.

Before the approval of fosdenopterin (Nulibry, Origin Biosciences), the only treatment options included supportive care and therapies directed towards the complications arising from the disease.

“Today’s action marks the first FDA approval for a therapy to treat this devastating disease,” Hylton V. Joffe, MD, MMSc, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research, said in the release. “The FDA remains committed to facilitating the development and approval of safe and effective therapies for patients affected by rare diseases — an area of critical need.”

Children with molybdenum cofactor deficiency type A cannot produce cyclic pyranopterin monophosphate (cPMP). Fosdenopterin replaces the missing cPMP. The effectiveness of the drug was demonstrated in 13 treated patients compared to 18 matched, untreated patients. Those treated with fosdenopterin had a survival rate of 84% at 3 years, compared with 55% for the untreated patients.

The most common side effects included complications related to the intravenous line, fever, respiratory infections, vomiting, gastroenteritis and diarrhea.
The FDA noted that phototoxicity was observed in animals, so patients treated with fosdenopterin should avoid exposure to sunlight and wear sunscreen, protective clothing, and sunglasses when exposed to the sun.

The FDA granted this application priority review and breakthrough therapy designations. Fosdenopterin also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. Origin Biosciences is also receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive priority review of a subsequent marketing application for a different product