Alexion Pharma International Sàrl, a subsidiary of Alexion Pharmaceuticals, Inc. has received a breakthrough therapy designation from the US Food and Drug Administration (FDA) for cyclic pyranopterin monophosphate (cPMP, or ALXN1101), an enzyme co-factor replacement therapy for the treatment of patients with molybdenum cofactor deficiency (MoCD) type A, a severe and life-threatening, ultra-rare, genetic metabolic disorder that causes catastrophic and irreversible neurologic damage within the first weeks of life.

According to the FDA, a Breakthrough Therapy designation is designed to expedite the development of a drug to treat a serious or life-threatening disease when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The Breakthrough Therapy designation is part of the FDA Safety and Innovation Act (FDASIA) of 2012.

“In designating cPMP as a Breakthrough Therapy, the FDA recognizes the life-threatening nature of MoCD Type A, the positive early clinical results associated with cPMP, and the lack of any effective treatment options for infants born with this devastating disease,” said Martin Mackay, Ph.D., executive vice president, global head of R&D at Alexion. “ALXN1101 is an innovative approach to the treatment of MoCD Type A, as it targets an essential step in the pathophysiology of the disease and the underlying cause of the disease by replacing the naturally occurring cPMP molecule, which is lacking in patients with MoCD Type A.”

Alexion looks forward to working closely with the FDA and obtaining FDA guidance on the subsequent development of ALXN1101 for the treatment of patients with MoCD Type A, including obtaining advice on generating evidence needed to support approval of the drug in an efficient manner. Alexion has initiated a natural history study in patients with MoCD Type A and has also completed dosing with the synthetic cPMP in a study in healthy volunteers.

MoCD Type A is a severe, ultra-rare and genetic metabolic disease affecting newborns in which a genetic deficiency of cPMP results in the inability of the body to form an essential cofactor called molybdenum cofactor, resulting in its absence. This cofactor is essential for the appropriate functioning of several critical metabolic enzymes. A deficiency or absence of this cofactor leads to accumulation of toxic molecules, including the neurotoxin sulfite. Clinically, the absence of this cofactor and the resulting build-up of sulfite in the brain lead to damage and destruction of nerve cells, brain swelling, uncontrollable seizures, catastrophic and irreversible brain damage, and ultimately, death.2 There are currently no treatment options for patients with MoCD Type A.

ALXN1101 is a synthetic version of cPMP and is designed to replace the naturally occurring cPMP lacking in infants with MoCD Type A. ALXN1101 restores the deficient enzyme activity which then causes clearance of the toxic metabolite sulfite thereby preventing the irreversible neurologic damage observed in untreated patients with MoCD Type A. Encouraging early clinical experience with an earlier form of cPMP replacement therapy has been reported by independent investigators in Germany and Australia.

Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on serving patients with severe and ultra-rare disorders through the innovation, development and commercialization of life-transforming therapeutic products.