Alexion Pharma (ALXN) Commences Two ALXN1210 Phase 3s

October 27, 2016 6:32 AM EDT

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Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) announced the initiation of two Phase 3 trials of ALXN1210, a highly innovative, longer-acting anti-C5 antibody that inhibits terminal complement. The first trial is a Phase 3 open-label, multinational, active-controlled study of ALXN1210 compared to eculizumab (Soliris®) in complement inhibitor treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH). Alexion has also accelerated the initiation of a registration trial of ALXN1210 in patients with atypical hemolytic uremic syndrome (aHUS). This second trial is a Phase 3, open-label, single arm, multinational trial to evaluate the safety and efficacy of ALXN1210 in complement inhibitor treatment-naïve adolescent and adult patients with aHUS. Both studies will evaluate ALXN1210 administered intravenously every eight weeks. Alexion expects to begin enrolling patients into these trials later this year, and plans to initiate a Phase 3 trial of ALXN1210 in pediatric patients with aHUS in 2017.

Alexion has also commenced dosing of a new formulation of ALXN1210 administered subcutaneously in healthy volunteers in a Phase I study.

PNH is a debilitating, ultra-rare and life-threatening blood disorder characterized by complement-mediated hemolysis (destruction of red blood cells).1 aHUS is a genetic, chronic, ultra-rare disease associated with vital organ failure and premature death.2,3,4 Both PNH and aHUS are caused by chronic uncontrolled complement activation.

“With more than 20 years of expertise in the discovery and development of complement inhibitors, our ongoing commitment is to bring even higher levels of innovation to patients with devastating ultra-rare diseases,” said Martin Mackay, Ph.D., Executive Vice President and Global Head of R&D at Alexion. “We are very pleased with our agreement with global regulators to progress ALXN1210 into Phase 3 studies in patients with PNH and aHUS and are now working with investigators to enroll patients into the registration studies with urgency.”

About the ALXN1210 PNH Study

The PNH trial is a Phase 3, randomized, open-label, active-controlled, multicenter 26-week study to evaluate the safety and efficacy of ALXN1210 compared to eculizumab in complement inhibitor treatment-naïve patients with PNH. The co-primary endpoints are the normalization of lactate dehydrogenase (LDH) levels and the percentage of patients who achieve transfusion avoidance (TA). Secondary endpoints include percentage change from baseline in LDH levels, change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, and percentage of patients with stabilized hemoglobin. The study is designed to evaluate the non-inferiority of ALXN1210 compared to eculizumab.

Patients in the ALXN1210 arm will receive a single loading dose of ALXN1210, followed by regular maintenance dosing every 8 weeks based on 3 weight cohorts. Patients in the eculizumab arm will receive 4 weekly induction doses, followed by regular maintenance dosing every 2 weeks. The multinational study will enroll approximately 214 adults (≥ 18 years of age) with a diagnosis of PNH who have never been treated with a complement inhibitor.

About the ALXN1210 aHUS Study

The aHUS trial is a Phase 3, open-label, single arm, multicenter 26-week study to evaluate the safety and efficacy of ALXN1210 in complement inhibitor treatment-naïve adolescent and adult patients with aHUS. The primary endpoint is complete thrombotic microangiopathy (TMA) response at 26 weeks. Secondary endpoints include dialysis requirement status, complete TMA response over time, observed value and change from baseline in estimated glomerular filtration rate, and change from baseline in chronic kidney disease stage, all evaluated at 26 weeks; time to complete TMA response; and additional efficacy measures. Patients will receive a single loading dose of ALXN1210, followed by regular maintenance dosing every 8 weeks based on 3 weight cohorts.

The multinational study will enroll approximately 55 adolescent (12 to < 18 years of age) and adult (≥ 18 years of age) patients with aHUS who have never been treated with a complement inhibitor.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH is an ultra-rare blood disorder in which chronic, uncontrolled activation of complement, a component of the normal immune system, results in hemolysis (destruction of the patient's red blood cells). PNH strikes people of all ages, with an average age of onset in the early 30s.1 Approximately 10 percent of all patients first develop symptoms at 21 years of age or younger.5 PNH develops without warning and can occur in men and women of all races, backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.6 In the period of time before Soliris® (eculizumab) was available, it had been estimated that approximately one-third of patients with PNH did not survive more than five years from the time of diagnosis.7 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).8,9,10 In patients with thrombosis of unknown origin, PNH may be an underlying cause.11

About aHUS

aHUS is a chronic, ultra-rare, and life-threatening disease in which a life-long and permanent genetic deficiency in one or more complement regulatory genes causes chronic uncontrolled complement activation, resulting in complement-mediated thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body.2,3 Permanent, uncontrolled complement activation in aHUS causes a life-long risk for TMA, which leads to sudden, catastrophic, and life-threatening damage to the kidney, brain, heart, and other vital organs, and premature death.2,4 Prior to the availability of Soliris, seventy-nine percent of all patients with aHUS died, required kidney dialysis or had permanent kidney damage within three years after diagnosis despite plasma exchange or plasma infusion (PE/PI).12 Moreover, 33 to 40 percent of patients died or progressed to end-stage renal disease with the first clinical manifestation of aHUS despite PE/PI.12,13 Prior to the availability of Soliris, the majority of patients with aHUS who received a kidney transplant commonly experienced subsequent systemic TMA, resulting in a 90 percent transplant failure rate in these TMA patients.14

aHUS affects both children and adults. Complement-mediated TMA also causes reduction in platelet count (thrombocytopenia) and red blood cell destruction (hemolysis). While mutations have been identified in at least ten different complement regulatory genes, mutations are not identified in 30-50 percent of patients with a confirmed diagnosis of aHUS.12,14,15

About ALXN1210

ALXN1210 is a highly innovative, longer-acting anti-C5 antibody discovered and developed by Alexion that inhibits terminal complement. In early studies, ALXN1210 demonstrated rapid, complete, and sustained reduction of free C5 activity.16 Alexion has completed enrollment in two ongoing clinical studies of ALXN1210 in patients with PNH—a Phase 1/2 dose-escalating study and an open-label, multi-dose Phase 2 study that is also evaluating longer dosing intervals beyond 8 weeks.

ALXN1210 is currently in Phase 3 trials in patients with PNH and aHUS. In addition, Alexion is conducting a Phase 1 study to evaluate a new formulation of ALXN1210 administered subcutaneously in healthy volunteers.

In June 2016, the European Commission granted Orphan Drug Designation (ODD) to ALXN1210 for the treatment of patients with PNH.

About Soliris® (eculizumab)

Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is approved in the U.S. (2007), European Union (2007), Japan (2010) and other countries as the first and only treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. PNH is a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is also approved in the U.S. (2011), European Union (2011), Japan (2013) and other countries as the first and only treatment for patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, or TMA (blood clots in small vessels). aHUS is a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated TMA. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). For the breakthrough medical innovation in complement inhibition, Alexion and Soliris have received some of the pharmaceutical industry's highest honors: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

More information, including the full U.S. prescribing information, on Soliris is available at www.soliris.net.



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