Other Therapeutic Candidates

Metabolic Disorders


Hypophosphatasia (HPP) is a genetic, chronic and progressive ultra-rare metabolic disease characterized by defective bone mineralization that can lead to destruction and deformity of bones, profound muscle weakness, seizures, respiratory failure and premature death. It is caused by a genetic deficiency of an enzyme known as tissue non-specific alkaline phosphatase (TNSALP), which causes life-long abnormalities in metabolism of the two vital minerals calcium and phosphate, leading directly to the debilitating morbidities and premature mortality of the disease.

Alexion is developing an investigational drug known as asfotase alfa, a first-in-class recombinant protein that addresses the underlying cause of HPP by targeting replacement of the missing enzyme to the necessary body tissues. In May 2013, Alexion recently received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for asfotase alfa, which is designed to normalize the genetically defective metabolic process and prevent or reverse the severe and life-threatening complications of life-long dysregulated mineral metabolism in patients with HPP.

In April 2014, Alexion initiated the rolling submission of a Biologics License Application (BLA) for asfotase alfa as a treatment for patients with HPP with the U.S. Food and Drug Administration (FDA). In July 2014, the Marketing Authorization Application (MAA) for asfotase alfa was validated and granted accelerated assessment by the European Medicines Agency (EMA), and in October 2014, Alexion submitted a New Drug Application (NDA) for asfotase alfa to Japan’s Ministry of Health, Labour and Welfare (MHLW).

Learn more about HPP

Molybdenum Cofactor Deficiency (MoCD) Type A

MoCD Type A is a severe, ultra-rare and genetic metabolic disease affecting newborns in which a genetic deficiency of cyclic pyranopterin monophosphate (cPMP) results in the inability of the body to form an essential cofactor called molybdenum cofactor. 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 leads to damage and destruction of nerve cells, brain swelling, uncontrollable seizures, catastrophic and irreversible brain damage, and ultimately, death. There are currently no treatment options for patients with MoCD Type A.

Alexion is working with research collaborators to accelerate the development of of ALXN1101, a synthetic version of cPMP 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.

Inflammatory Disorders

Alexion is also investigating new therapeutic agents designed to regulate the complement inflammatory pathway. These include ALXN1007, a novel anti-inflammatory antibody designed to target severe and ultra-rare inflammatory disorders. Currently, ALXN1007 is being evaluated in a Phase 2 proof-of-concept study in patients with a rare autoimmune disorder called antiphospholipid syndrome (APS), and in another Phase 2 proof-of-concept study in patients with another severe and ultra-rare disorder, graft-versus-host disease involving the lower gastrointestinal tract, or GI-GVHD.