Fosdenopterin 9.5mg powder for solution for injection vials

Molybdenum cofactor deficiency (MoCD) is an exceptionally rare autosomal recessive disorder resulting in a deficiency of three molybdenum-dependent enzymes: sulfite oxidase (SOX), xanthine dehydrogenase, and aldehyde oxidase.[A230088] Signs and symptoms begin shortly after birth and are caused by a build-up of toxic sulfites resulting from a lack of SOX activity.[A230088][L32163] Patients with MoCD may present with metabolic acidosis, intracranial hemorrhage, feeding difficulties, and significant neurological symptoms such as muscle hyper- and hypotonia, intractable seizures, spastic paraplegia, myoclonus, and opisthotonus. In addition, patients with MoCD are often born with morphologic evidence of the disorder such as microcephaly, cerebral atrophy/hypodensity, dilated ventricles, and ocular abnormalities.[A230088] MoCD is incurable and median survival in untreated patients is approximately 36 months[A230088] - treatment, then, is focused on improving survival and maintaining neurological function.

The most common subtype of MoCD, type A, involves mutations in MOCS1 wherein the first step of molybdenum cofactor synthesis - the conversion of guanosine triphosphate into cyclic pyranopterin monophosphate (cPMP) - is interrupted.[A230088][A230593] In the past, management strategies for this disorder involved symptomatic and supportive treatment,[L32163] though efforts were made to develop a suitable exogenous replacement for the missing cPMP. In 2009 a recombinant, E. coli-produced cPMP was granted orphan drug designation by the FDA, becoming the first therapeutic option for patients with MoCD type A.[A230088]

Fosdenopterin was approved by the FDA on Februrary 26, 2021, for the reduction of mortality in patients with MoCD type A,[L32163] becoming the first and only therapy approved for the treatment of MoCD. By improving the three-year survival rate from 55% to 84%,[L32288] and considering the lack of alternative therapies available, fosdenopterin appears poised to become a standard of therapy in the management of this debilitating disorder.

In July 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended fosdenopterin be granted marketing authorization under exceptional circumstances for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A.[L43075] In September 2022, the EMA approved the use of fosdenopterin.[L43372][L43433]