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. HPP is caused by mutations in the gene encoding an enzyme known as tissue non-specific alkaline phosphatase (TNSALP). The genetic deficiency in HPP can affect people of all ages. HPP is classified by the age of the patient at the onset of symptoms of the disease, and infantile- and juvenile-onset HPP is defined as manifestation of the first symptom prior to 18 years of age.

HPP can have devastating consequences for patients at any stage of life. In a natural history study, infants who had their first symptom of HPP within the first 6 months of life had high mortality, with an overall mortality rate of 73% at 5 years. In these patients, mortality is primarily due to respiratory failure. In patients surviving to adolescence and adulthood, long-term clinical sequelae include recurrent and non-healing fractures, debilitating weakness, severe pain and the requirement for ambulatory assistive devices such as wheelchairs, wheeled walkers and canes.

Alexion is developing an investigational drug known as asfotase alfa, a first-in-class enzyme replacement therapy. Asfotase alfa is designed to address the underlying cause of HPP by aiming to restore the genetically defective metabolic process, thereby preventing or reversing the severe and potentially life-threatening complications of life-long dysregulated mineral metabolism.

In 2013, the FDA granted Breakthrough Therapy designation for asfotase alfa. 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. In 2014, Alexion filed for regulatory approval for asfotase alfa as a treatment for HPP with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and 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. To learn more visit AlexionClinicalTrials.com.