– At 26 weeks, 54% of adults and 71% of children treated with ULTOMIRIS demonstrated Complete Thrombotic Microangiopathy (TMA) Response –

BOSTON, MA, USA I October 18, 2019 IAlexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that the U.S. Food and Drug Administration (FDA) approved ULTOMIRIS® (ravulizumab-cwvz) for the treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) for adult and pediatric (one month of age and older) patients. This is the first pediatric approval for ULTOMIRIS. Atypical HUS is an ultra-rare disease that can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots. Atypical HUS can cause sudden organ failure or a slow loss of function over time—potentially resulting in the need for a transplant, and in some cases, death.

“The primary approach to treatment is to prevent the body from attacking itself, through the inhibition of uncontrolled complement activation, referred to as C5 inhibition,” said Spero Cataland, M.D., Professor of Clinical Internal Medicine, Wexner Medical Center, The Ohio State University College of Medicine. “Clinical study results showed adult and pediatric patients had complete C5 inhibition following the first dose of ULTOMIRIS. C5 inhibition was sustained over time with only six or seven infusions a year in adults—and that is important to consider for my patients.”

Atypical HUS affects both adults and children and many patients present in critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of aHUS can be poor in many cases, so a timely and accurate diagnosis—in addition to treatment—is critical to improving patient outcomes.

“The consequences of uncontrolled complement activation, like organ failure and potentially death, create significant challenges and uncertainty for people and families facing aHUS,” said John Orloff, M.D., Executive Vice President and Head of Research and Development at Alexion. “Based on the Phase 3 data, which demonstrated clinically meaningful benefits in people with aHUS, we believe ULTOMIRIS has the potential to become the new standard of care for this devastating disease.”

The FDA approval is based on data from two global, single-arm open-label studies of ULTOMIRIS – one in adults and one in children, referred to as pediatrics in the study – with aHUS. The pediatric study is ongoing and a total of 14 out of 16 children were enrolled and included in the interim analysis. Efficacy evaluation of Complete TMA Response was defined by hematologic normalization parameters (platelet count and LDH) and improved kidney function (as measured by ≥ 25 percent improvement in serum creatinine from baseline). In the initial 26-week treatment periods, 54 percent of adults and 71 percent (interim data) of children demonstrated Complete TMA Response. Treatment with ULTOMIRIS resulted in reduced thrombocytopenia (low blood platelet count) in 84 percent of adults and 93 percent of children, reduced hemolysis (the destruction of red blood cells) in 77 percent of adults and 86 percent of children, and improved kidney function in 59 percent of adults and 79 percent (interim data) of children (for patients on dialysis at enrollment, baseline was established after they had come off dialysis).

The most frequently observed adverse reactions reported in these studies were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious meningococcal infections have occurred in patients treated with ULTOMIRIS. To minimize the risk for patients, specific risk-mitigation plans, including a REMS, have been established for ULTOMIRIS.

Regulatory filings for marketing authorizations of ULTOMIRIS for the treatment of aHUS in the European Union (EU) and Japan are under review with regulators.

About aHUS
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease that affects both children and adults and can lead to potentially irreversible damage to kidneys and other vital organs, sudden or progressive kidney failure (requiring dialysis or transplant) and premature death. aHUS is characterized by inflammation and the formation of blood clots in small blood vessels throughout the body (thrombotic microangiopathy [TMA]) mediated by chronic, uncontrolled activation of the complement system, which is part of the body’s immune system. TMA consists of reduced platelet count (thrombocytopenia), hemolytic anemia (as a result of hemolysis [destruction of red blood cells]) and acute kidney injury (AKI). If left untreated, significant proportions of adults (46 percent) and children (16 percent) can progress to end-stage renal disease (ESRD) or die during first clinical manifestations of aHUS despite supportive care, including plasma exchange or plasma infusion (PE/PI). One year following clinical manifestations, 56 percent of adults and 29 percent of children can progress to ESRD or die, if left untreated. Early and careful diagnosis of aHUS is critical, as many coexisting diseases and events are known or suspected to activate the complement cascade, and as patients may not necessarily present with the classic TMA triad of thrombocytopenia, hemolytic anemia and renal impairment or may have less severe renal involvement. Available tests can help distinguish aHUS from other hemolytic diseases with similar symptoms such as HUS caused by Shiga toxin-producing Escherichia coli (STEC-HUS) and thrombotic thrombocytopenic purpura (TTP).

About ULTOMIRIS
ULTOMIRIS (ravulizumab-cwvz) is the first and only long-acting C5 complement inhibitor. It is administered intravenously every eight weeks or every four weeks for pediatric patients less than 20 kg, following a loading dose. ULTOMIRIS works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. The terminal complement cascade, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders. ULTOMIRIS is approved in the U.S., Japan, and the EU as a treatment for adults with PNH and in the U.S. for aHUS to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients.

You can read more about the study results for this clinical program on alexion.com.

INDICATIONS & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS (ravulizumab-cwvz) 300 mg / 30 mL injection for intravenous use

INDICATIONS
ULTOMIRIS is a prescription medicine called a monoclonal antibody. ULTOMIRIS is used to treat adults with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH). ULTOMIRIS is used to treat adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). It is not known if ULTOMIRIS is safe and effective in children with PNH. It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age.

About Alexion
Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the discovery, development and commercialization of life-changing therapies. As the global leader in complement biology and inhibition for more than 20 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D). In addition, the company is developing several mid-to-late-stage therapies, including a second complement inhibitor, a copper-binding agent for Wilson disease and an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases as well as several early-stage therapies, including one for light chain (AL) amyloidosis and a second anti-FcRn therapy. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, and metabolic disorders. Alexion has been named to the Forbes’ list of the World’s Most Innovative Companies seven years in a row and is headquartered in Boston, Massachusetts’ Innovation District. The company also has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: www.alexion.com.

SOURCE: Alexion Pharmaceuticals