General Information

Nulibry (fosdenopterin) is cyclic pyranopterin monophosphate (cPMP). Patients with Molybdenum Cofactor Deficiency Type A cannot produce cPMP.

Nulibry is specifically indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) Type A.

Nulibry is supplied as a solution for intravenous infusion. Start Nulibry if the patient has a diagnosis or presumptive diagnosis of MoCD Type A. In patients with a presumptive diagnosis of MoCD Type A, confirm the diagnosis of MoCD Type A immediately after initiation of Nulibry treatment. In such patients, discontinue Nulibry if the MoCD Type A diagnosis is not confirmed by genetic testing. Nulibry is given through an infusion pump at a rate of 1.5 mL per minute. Dose volumes below 2 mL may require syringe administration through slow intravenous push. Administration of Nulibry must be completed within 4 hours of reconstitution.

The recommended dosage regimen of Nulibry in patients less than one year of age (by gestational age) is based on actual body weight:

Preterm Neonates (Gestational Age Less than 37 Weeks):

Initial Dosage 0.4 mg/kg once daily

Dosage at Month 1 0.7 mg/kg once daily

Dosage at Month 3 0.9 mg/kg once daily

Term Neonates (Gestational Age 37 Weeks and Above)

Initial Dosage: 0.55 mg/kg once daily

Dosage at Month 1: 0.75 mg/kg once daily

Dosage at Month 3: 0.9 mg/kg once daily

For patients one year of age or older, the recommended dosage of Nulibry is 0.9 mg/kg (based on actual body weight) administered as an intravenous infusion once daily.

If a Nulibry dose is missed, administer the missed dose as soon as possible. Administer the next scheduled dose at least 6 hours after the administration of the missed dose.

Mechanism of Action

Nulibry (fosdenopterin) is cyclic pyranopterin monophosphate (cPMP). Patients with MoCD Type A have mutations in the MOCS1 gene leading to deficient MOCS1A/B dependent synthesis of the intermediate substrate, cPMP. Substrate replacement therapy with Nulibry 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 (SOX), an enzyme that reduces levels of neurotoxic sulfites.

Clinical Trial Results

The FDA approval of Nulibry was based on data from three clinical studies (Studies 1, 2, and 3) that were compared to data from a natural history study.

Study 1 was a prospective, open-label, single-arm, dose escalation study in patients with MoCD Type A who were receiving treatment with rcPMP prior to treatment with Nulibry. The study included 8 patients, 6 of whom previously participated in Study 3. The initial Nulibry dosage was matched to the patient’s rcPMP dosage upon entering the study. The Nulibry dosage was then titrated over a period of 5 months to a maximum dosage of 0.9 mg/kg administered once daily as an intravenous infusion.

Study 2 was a prospective, open-label, single-arm, dose escalation study in one patient with MoCD Type A who had not been previously treated with rcPMP. The initial dosage of Nulibry was based on the gestational age of the patient (i.e., 36 weeks). The initial dosage was then incrementally escalated up to a maximum dosage of 0.98 mg/kg administered once daily as an intravenous infusion (1.1 times the maximum approved recommended dosage).

Study 3 was a retrospective, observational study that included 10 patients with a confirmed diagnosis of MoCD Type A who received rcPMP. Six of these 10 patients were later enrolled in Study 1 to receive treatment with Nulibry.

The effectiveness of Nulibry for the treatment of Molybdenum Cofactor Deficiency Type A was demonstrated in 13 treated patients compared to 18 matched, untreated patients. The patients treated with Nulibry had a survival rate of 84% at three years, compared to 55% for the untreated patients.