Rare Daily Staff

The European Commission has granted marketing authorization to Nulibry for Injection as the first therapy for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A.

The approval was granted to Sentynl Therapeutics, a U.S.-based biopharmaceutical company owned by Zydus Lifesciences, which acquired global rights to Nulibry from BridgeBio Pharma in March 2022.

MoCD Type A is an ultra-rare and progressive condition known to impact less than 150 patients globally with a median survival of four years. MoCD Type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production, leading to a lack of molybdenum-dependent enzyme activity. The lack of activity leads to decreased sulfite oxidase activity with buildup of sulfite and secondary metabolites in the brain, which causes irreversible neurological damage.

The most common presenting symptoms of MoCD Type A are seizures, feeding difficulties and encephalopathy. Patients with MoCD Type A who survive beyond infancy typically suffer from progressive brain damage, which presents in characteristic patterns on magnetic resonance imaging (MRI). This damage leads to severe psychomotor impairment and an inability to make coordinated movements or communicate with their environment.

Nulibry for Injection is a substrate replacement therapy that provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase, an enzyme that reduces levels of neurotoxic sulfites. It is the first and only FDA-approved therapy indicated to reduce the risk of mortality in patients with MoCD Type A, and clinical trials have demonstrated that patients treated with NULIBRY or rcPMP had an improvement in overall survival compared to the untreated, genotype-matched, historical control group.

The U.S. Food and Drug Administration approved Nulibry in 2021 to reduce the risk of mortality in patients with MoCD Type A. Following this decision by the European Commision, Nulibry is the first and only approved therapy in the European Union for MoCD Type A.

The EC authorization follows the positive opinion granted by European Committee for Medicinal Products for Human Use in July 2022, which was supported by data from three clinical trials that demonstrated the efficacy of Nulibry for the treatment of patients with MoCD Type A compared to data from a natural history study. These studies showed that in the genotype-matched analysis, patients treated with Nulibry had 7.1 times lower risk of death than their historical control counterparts from the natural history study, with 86 percent of Nulibry-treated patients surviving at three years compared to 52 percent of the genotype-matched control group.

“This is a major milestone for those patients living with MoCD Type A in Europe,” said Matt Heck, CEO of Sentynl. “Marketing authorization is an important step in providing access to Nulibry and creating awareness of MoCD Type A as many patients are often missed.”

In March 2022, Sentynl acquired the global rights to Nulibry and is responsible for the ongoing development and commercialization of Nulibry in the United States and developing, manufacturing, and commercializing fosdenopterin globally. Sentynl and BridgeBio share development responsibilities through the approval of the marketing authorization application under accelerated assessment with the European Medicines Agency (EMA) and through approval of Nulibry’s regulatory submission with the Israeli Ministry of Health.

The European Commission’s centralized marketing authorization is valid in all EU member states as well as Iceland, Liechtenstein, and Norway. A regulatory filing is expected in the coming months to the UK’s Medicine and Healthcare products Regulatory Agency (MHRA) as part of the European Commission Decision Reliance Procedure. Sentynl expects to make Nulibry available following successful completion of country-by-country health authority discussions. Until such time, Nulibry will be made available to qualified patients through an Early Access Program.

Photo: Matt Heck, CEO of Sentynl

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