– Final European Commission decision anticipated in June 2019 –

– ULTOMIRIS has the potential to become the new standard of care for both complement inhibitor-naïve patients and patients switching from SOLIRIS® (eculizumab) –

BOSTON, MA, USA & ZURICH, Switzerland I April 26, 2019 I Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending marketing authorization for ULTOMIRIS® (ravulizumab), the first and only long-acting C5 complement inhibitor administered every eight weeks. The recommended indication is for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) with haemolysis with clinical symptoms indicative of high disease activity,1 and also for adult patients who are clinically stable2 after having been treated with SOLIRIS® (eculizumab) for at least the past six months. PNH is a severe, complement-mediated ultra-rare disease that can cause a wide range of debilitating symptoms and complications, including thrombosis, which can occur throughout the body and result in organ damage and premature death.3,4,5,6,7,8,9,10

“This critical milestone brings us one step closer to our goal of bringing ULTOMIRIS to patients with PNH in the EU,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “Immediate and complete C5 inhibition sustained for eight weeks can provide meaningful benefits for patients and their families. ULTOMIRIS has the potential to become the new standard of care for patients with PNH based on the totality of our Phase 3 data and the reduction from 26 infusions per year with SOLIRIS to only six or seven for ULTOMIRIS.”

The CHMP opinion is based on comprehensive results from two Phase 3 studies, which represent the largest Phase 3 program ever conducted in PNH.11,12 In these studies, which included more than 440 patients who had either never been treated with a complement inhibitor before,11 or who had been stable on SOLIRIS,12 the efficacy of ULTOMIRIS administered every eight weeks was non-inferior to the efficacy of SOLIRIS administered every two weeks on all 11 endpoints. The safety profile of ULTOMIRIS was similar to that of SOLIRIS. Additional data showed that ULTOMIRIS provided immediate and complete C5 inhibition that was sustained for eight weeks,13 and that ULTOMIRIS eliminated breakthrough hemolysis associated with incomplete C5 inhibition.14 The entire clinical development program for ULTOMIRIS in PNH to date represents more than 750 patient years of experience.

The European Commission will review the CHMP recommendation and typically delivers its final decision within two months. The U.S. Food and Drug Administration (FDA) approved ULTOMIRIS (ravulizumab-cwvz) for adult patients with PNH on December 21, 2018. Regulatory authorities in Japan are reviewing Alexion’s application for the approval of ULTOMIRIS as a treatment for patients with PNH.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating and life-threatening ultra-rare blood disorder characterized by hemolysis (destruction of red blood cells) that is mediated by an uncontrolled activation of the complement system, a component of the body’s immune system.3,4,15 PNH can strike men and women of all races, backgrounds and ages without warning, with an average age of onset in the early 30s.3,16 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than five years.17 Patients with PNH may experience a wide range of signs and symptoms, such as fatigue, difficulty swallowing, shortness of breath, abdominal pain, erectile dysfunction, dark-colored urine and anemia.5,6,7,8,9,10,15 The most devastating consequence of chronic hemolysis is thrombosis, which can occur in blood vessels throughout the body, damage vital organs and cause premature death.18 The first thrombotic event can be fatal.3,16,19 Despite historical supportive care, including transfusion and anticoagulation management, 20 to 35 percent of patients with PNH die within five to 10 years of diagnosis.20,21 Patients with certain types of hemolytic anemia, bone marrow disorders and unexplained venous or arterial thrombosis are at increased risk of PNH.15,22,23,24,25,26

About ULTOMIRIS®
ULTOMIRIS (ravulizumab-cwvz), the first and only long-acting C5 inhibitor administered every eight weeks, is approved in the U.S. as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH). 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 like PNH, atypical hemolytic uremic syndrome (aHUS), anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG) and anti-aquaporin-4 (AQP4) auto-antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Regulatory authorities in the European Union (EU) and Japan are reviewing applications for the approval of ULTOMIRIS as a treatment for adult patients and patients with PNH, respectively. In Phase 3 clinical studies in complement inhibitor-naïve patients with PNH11 and patients with PNH who had been stable on SOLIRIS® (eculizumab),12 intravenous treatment with ULTOMIRIS every eight weeks demonstrated non-inferiority to intravenous treatment with SOLIRIS every two weeks on all 11 endpoints.

The Phase 3 study of ULTOMIRIS, administered intravenously every eight weeks in adult patients with aHUS, met its primary objective. Alexion has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for approval of ULTOMIRIS as a treatment for patients with aHUS and plans to submit similar applications in the EU and Japan later in 2019. ULTOMIRIS is also currently being evaluated in a Phase 3 clinical study in children and adolescents with aHUS, administered intravenously every eight weeks. Alexion has initiated a Phase 3 study of ULTOMIRIS, intravenously administered every eight weeks, as a potential treatment for patients with generalized MG (gMG), and is planning to initiate a Phase 3 in patients with NMOSD. In addition, Alexion has initiated Phase 3 studies of ULTOMIRIS delivered subcutaneously once per week as a potential treatment for patients with PNH, aHUS and gMG.

ULTOMIRIS has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU and Japan and for the subcutaneous treatment of patients with aHUS in the U.S.

U.S. Indication of ULTOMIRIS® (ravulizumab-cwvz)
ULTOMIRIS is a prescription medicine called a monoclonal antibody. ULTOMIRIS is used to treat adults with a disease called paroxysmal nocturnal hemoglobinuria (PNH). It is not known if ULTOMIRIS is safe and effective in children.

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) as well as the first and only approved complement inhibitor to treat atypical hemolytic uremic syndrome (aHUS) and anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG), and is also developing it for patients with 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.

References
1   With high disease activity defined as lactate dehydrogenase (LDH) levels (a direct marker of haemolysis) ≥ 1.5 × upper limit of normal (ULN) at screening along with the presence of one or more of the following PNH-related signs or symptoms within three months of screening: fatigue, haemoglobinuria, abdominal pain, shortness of breath (dyspnoea), anaemia (haemoglobin < 10 g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction, or history of packed red blood cell transfusion due to PNH.
2   With clinically stable defined as LDH levels ≤ 1.5 x ULN.
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SOURCE: Alexion Pharmaceuticals