Eculizumab in Other Diseases

Transplant

Antibody-Mediated Rejection (AMR)

Acute antibody-mediated rejection (AMR) 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. Research suggests that uncontrolled complement activation, triggered by the binding of donor-specific antibodies (DSAs) to target proteins in the donor kidney, may be the primary cause of acute AMR in kidney transplant recipients.

Sensitized patients—those who have high levels of DSAs—are at high risk for developing AMR. 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. Due to the risk of AMR, sensitized patients may have difficulty finding a viable donor organ, and therefore may never become eligible for transplantation or may face significant delays in finding a suitable transplant. Instead, these patients remain on dialysis, which carries a very high mortality risk. In fact, approximately 65% of patients die within 5 years of commencing dialysis.

There remains an urgent need for a therapy that prevents AMR and enables transplantation in sensitized patients with end stage renal disease. Alexion is studying eculizumab for the prevention of AMR in patients receiving kidney transplants. Visit clinicaltrials.gov to learn more.

Delayed Graft Function (DGF)

Delayed graft function (DGF) is an early and serious complication of organ transplantation in which a transplanted kidney, known as a graft, does not function normally immediately following transplantation. Patients experiencing DGF after a kidney transplant require dialysis in order to survive, and the condition can be life-threatening due to the risk of losing the transplanted organ.

DGF affects approximately 25 percent, and possibly up to 50 percent, of deceased-donor kidney transplant cases. DGF typically results from ischemia/reperfusion injury (IRI), which is due to multiple processes that occur following the restoration of blood flow to an area that had previously experienced deficient blood flow. Uncontrolled complement activation following IRI is believed to play a major role in the development of DGF.

There remains an urgent need for an innovative therapy to prevent DGF, which currently has no approved treatment options. Because donor organs are in short supply, reducing the risk of DGF for organs that are at higher risk of developing this devastating complication may allow more donor organs to be transplanted. Alexion is studying eculizumab for the prevention of DGF in patients receiving kidney transplants. Visit clinicaltrials.gov to learn more.

Neurology

Neuromyelitis Optica (NMO)

Neuromyelitis optica (NMO) is a life-threatening, ultra-rare neurological disorder. In patients with NMO, chronic, 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.

NMO is characterized by severe weakness, paralysis, respiratory failure, loss of bowel and bladder function, blindness and premature death. Patients with NMO have lifelong exposure to uncontrolled terminal 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.

Currently, there are no approved treatment options for NMO. Alexion has a clinical trial under way called the PREVENT (Prevention of Relapses and EValuation of Eculizumab in NMO Treatment) study to evaluate the safety and efficacy of eculizumab as a potential treatment for patients with relapsing NMO. To learn more about PREVENT, visit clinicaltrials.gov (identifier NCT01892345).

Myasthenia Gravis (MG)

Myasthenia gravis (MG) is a rare, debilitating, neurological disorder caused by uncontrolled complement activation that results from auto-antibodies recognizing a specific target in the nerve-muscle junction, causing tissue damage and interference with signaling between nerve and muscle fibers. Patients with MG 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, which could lead to a life-threatening myasthenic crisis.

There is no known cure for MG. Common treatments include medications (anticholinesterase agents, corticosteroids, immunosuppressive agents or cytotoxic therapy), thymectomy (surgical removal of the thymus gland) and plasma exchange. Alexion has a clinical trial under way called the REGAIN (Eculizumab for REfractory GenerAlIzed MyastheNia Gravis) study to evaluate the safety and efficacy of eculizumab as a potential treatment for patients with refractory generalized MG. To learn more about REGAIN, visit clinicaltrials.gov (identifier NCT01997229).