This approval marks the first treatment indicated for reducing mortality risk in patients with the rare disorder known as molybdenum cofactor deficiency (MoCD) Type A.
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The U.S. Food and Drug Administration (FDA) has approved BridgeBio Pharma and its affiliate Origin Biosciences’ injectable, rare genetic metabolic disorder therapy NULIBRY™ (fosdenopterin). This approval marks the first treatment indicated for reducing mortality risk in patients with the rare disorder known as molybdenum cofactor deficiency (MoCD) Type A.
An ultra-rare and progressive disease, MoCD Type A affects fewer than 150 patients across the globe. Overall, the median survival following diagnosis is approximately four years. The condition is observed shortly after birth and typically accompanies symptoms such as severe encephalopathy and intractable seizures.
BridgeBio’s Origin submitted a new drug application with the FDA for the therapy back in December 2019. The FDA reviewed NULIBRY under Priority Review, and the therapy received Orphan Drug Designation, Breakthrough Therapy Designation and Rare Pediatric Disease Designation. In addition, the agency issued a Rare Pediatric Disease Priority Review Voucher (PRV) to Origin.
“Today’s action marks the first FDA approval for a therapy to treat this devastating disease,” according to a statement made by Hylton V. Joffe, M.D., M.M.Sc, the director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research. “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.”
“The FDA’s approval of NULIBRY means that patients with MoCD Type A and their families have an approved therapy for the first time,” said BridgeBio founder and Chief Executive Officer Neil Kumar, Ph.D. “It also reflects our belief that every life matters and that no disease is too rare to address. As is often true in rare disease drug development, this was a community effort in which we were able to play a part – we’d like to thank the patients, caregivers, physicians, scientists, and advocates who played an essential role in achieving this important milestone.”
Data from three clinical trials, which were compared with data from a natural history study, established the efficacy of NULIBRY for reducing mortality risk in patients with MoCD Type A.
The studies saw that treatment with NULIBRY or recombinant cPMP, which features the same biologic activity as NULIBRY, was associated with a reduction in the risk of death by 82% compared with untreated patients in the natural historical control study. The survival probability among patients treated with NULIBRY or recombinant cPMP at three years was 84% versus 55% in the untreated genotype-matched patients in the natura history study.
Treatment with NULIBRY in the three studies was also associated with a marked reduction in urine concentrations of S-sulfocysteine (SSC), a toxic substance that is associated with neurological damage in patients with MoCD Type A. The studies show that the reduction in SSC was sustained over 48 months with long-term NULIBRY therapy.
Animal studies suggest NULIBRY features phototoxic potential. Clinical trials found that catheter-related complications (89%), pyrexia (fever; 78%), viral infection (56%), pneumonia (44%), ear infection (44%), vomiting (44%) and cough/sneezing (44%) were the most common adverse events reported in two or more patients with MoCD Type A treated with NULIBRY.
“Today’s approval represents new hope for patients and families affected with MoCD Type A,” added Donald Basel, M.D., section chief and associate professor of pediatrics at Children’s Wisconsin. “I am encouraged by the clinical data showing that NULIBRY not only lowers the levels of toxic SSC, but importantly extends the lives of patients who previously had only a three- to four-year median survival.”
