Eculizumab in Other Diseases

Transplant

Antibody-Mediated Rejection (AMR)

Alexion is studying eculizumab for the prevention of antibody-mediated rejection in patients receiving kidney transplants.

Antibody-mediated rejection is a severe and potentially life-threatening condition that can lead to severe kidney allograft damage resulting in rapid loss of function and possible loss of the transplanted kidney. Patients who are sensitized (have high levels of donor-specific-antibodies or DSAs) are at high risk for developing AMR, may have difficulty finding a viable donor organ, and therefore may never become eligible for transplantation. The development of AMR is believed to be primarily a result of uncontrolled complement activation caused by DSA, which in turn frequently results in allograft damage and dysfunction, potential graft loss, and/or shortened graft survival.

While solid organ transplantation is the most effective form of therapy for the treatment of patients with end-stage renal disease (ESRD), concern about the consequences of AMR remains a significant obstacle to transplantation, as it results in significant delays for affected patients to access to a suitable transplant. Overall, dialysis remains a very high mortality outcome for patients with ESRD, since, approximately 65% of patients die within 5 years of commencing dialysis. Additionally, approximately one-third of patients on the kidney transplant waiting list are sensitized to their potential donors and historically, approximately 30% of this highly sensitized population has developed AMR. A therapy that prevents AMR is critically important for sensitized patients with ESRD. Currently, there are no approved therapies for the prevention of AMR.

Delayed Graft Function (DGF)

Alexion is studying eculizumab as a potential treatment for delayed graft function (DGF), a condition in which a transplanted kidney, known as a graft, does not initially function properly. As a result, patients must undergo dialysis for a period of time following the transplant surgery.

Neurology

Alexion is studying eculizumab as a potential treatment for patients with rare and serious neurologic disorders, including relapsing neuromyelitis optica (NMO) and refractory myasthenia gravis (MG).

Neuromyelitis Optica (NMO)

Neuromyelitis optica (NMO) is a life-threatening, ultra-rare neurological disorder. In patients with NMO, uncontrolled complement activation causes destruction of cells that produce myelin, a substance that surrounds nerve fibers and helps nerve signals move from cell to cell. This results in severe damage to the central nervous system (CNS), including the spinal cord and optic nerve. The disease leads to severe weakness, paralysis, respiratory failure, loss of bowel and bladder function, blindness and premature death. Patients with NMO have a life-long exposure to the uncontrolled complement activation due to chronic autoimmune attack, and most patients experience an unpredictable, relapsing course of disease with cumulative disability, as each attack adds to the neurologic disability. Fifty percent of relapsing NMO patients have been reported to sustain permanent severe disability, including paralysis and blindness, within five years of disease onset. Most NMO-related deaths result from respiratory complications from NMO attacks. The disease primarily affects women, with a female to male ratio as high as a 9:1.

Myasthenia Gravis (MG)

Myasthenia Gravis is a rare, debilitating, neurological disorder caused by uncontrolled complement activation. The uncontrolled complement activation, resulting from auto-antibodies that recognize a specific target in the nerve-muscle junction, causes tissue damage and interference with signaling between nerve and muscle fibers. Patients with myasthenia gravis initially experience weakness in their ocular (eye) muscles, and the disease typically progresses to the more severe and generalized form to include head, spinal, limb and respiratory muscles. Symptoms can include drooping eyelid, blurred vision, slurred speech, difficulty chewing or swallowing, weakness in the arms and legs and difficulty breathing. There is no known cure for myasthenia gravis. Common treatments include medications (anticholinesterase agents, corticosteroids, immunosuppressive agents or cytotoxic therapy), thymectomy (surgical removal of the thymus gland) and plasma exchange.