– Global study to enroll approximately 270 adults with COVID-19 and severe pneumonia or acute respiratory distress syndrome –

– Company maintains commitment to supplying its medicines to patients for currently approved indications –

BOSTON, MA, USA I April 20, 2020 IAlexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced plans to initiate a global Phase 3 study to investigate ULTOMIRIS® (ravulizumab-cwvz) in a subset of adults with COVID-19 – those who are hospitalized with severe pneumonia or acute respiratory distress syndrome (ARDS). The study is expected to enroll approximately 270 patients across countries with high numbers of diagnosed cases, beginning in May, and will evaluate the impact of ULTOMIRIS, a biologic medicine, on survival, duration of mechanical ventilation, and hospital stay compared to best supportive care. This follows the U.S. Food and Drug Administration’s (FDA) rapid review and acceptance of Alexion’s investigational new drug (IND) application for ULTOMIRIS for severe COVID-19.

“Alexion has been in close contact with physicians and global health authorities in an effort to rapidly evaluate the potential of C5 inhibition in treating patients with severe COVID-19,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “Based on early anecdotal information available from compassionate use cases in multiple countries, we are launching a controlled clinical trial to evaluate the potential of ULTOMIRIS in mitigating the severe pneumonia and lung injury caused by the virus. As we move quickly to initiate this program, we also remain committed to serving the patients who currently rely on our medicines and providing continuous supply to these patients.”

The decision to begin this trial is based on a) published preclinical data suggesting that inhibition of terminal complement can lower cytokine and chemokine levels and significantly reduce lung inflammation and pathology in animal models of viral pneumoniai, and b) elevated complement biomarkers and promising preliminary clinical evidence from patients who have accessed SOLIRIS® (eculizumab) through our compassionate use program, which suggests that complement inhibition may improve coronaviral-mediated lung injury.

Independent investigators have expressed interest in studying the potential of C5 inhibition in severe COVID-19 pneumonia, and we are aware of several ongoing or planned independent studies and anecdotal results from the use of our C5 inhibitors in patients with COVID-19. While these healthcare professionals continue to aggregate data regarding the potential of terminal complement inhibition in COVID-19 pneumonia from the approximately 100 patients who have been treated so far, Alexion believes that the outcomes reported to date warrant conducting a controlled clinical program to explore the impact of C5 inhibition with ULTOMIRIS and establish clinical evidence supporting the role of terminal complement in coronaviral pneumonia. We believe ULTOMIRIS represents the future of C5 inhibition, with its weight-based dosing, reduced burden on hospital systems due to less frequent dosing and it can be manufactured at a higher capacity, providing the opportunity to better meet future supply demands.

For additional information on Alexion’s ongoing efforts related to COVID-19, please visit: https://alexion.com/our-commitment/covid-19.

About the Phase 3 Study

The Phase 3 open-label, randomized, controlled study is designed to evaluate the safety and efficacy of ULTOMIRIS in approximately 270 adults hospitalized with COVID-19 and severe pneumonia, acute lung injury or acute respiratory distress syndrome (ARDS). Study participants will be randomized 2:1 to receive ULTOMIRIS or best supportive care. The primary endpoint is survival at Day 29. Secondary endpoints will assess the need for mechanical ventilation, oxygenation, duration of ICU stay and hospitalization, and safety, among others.

Patients in the ULTOMIRIS arm will receive a weight-based loading dose of ULTOMIRIS on Day 1 (2400mg for patients weighing 40-60kg, 2700mg for 60-100kg, or 3000mg for ≥100kg). Follow-up dosing on Days 5, 10 and 15 will also be weight-based; patients weighing 40 to 60kg will receive 600mg of ULTOMIRIS and patients weighing 60kg or more will receive 900mg of ULTOMIRIS. All patients will continue to receive medications, therapies, and interventions per standard hospital treatment protocols for the duration of the study. Following the 4-week treatment period, there will be safety follow-up monitoring for three months.

Expanded Access Programs

In recognition of the urgent needs of some patients and in order to streamline the emergency access process, Alexion has opened emergency Expanded Access Programs (EAP) in the U.S. and France for SOLIRIS in severe COVID-19 pneumonia. All requests for a hospital to be included in the EAP must be made by a treating physician and can be submitted to covid.requests@alexion.com.

Access & Supply Considerations

Alexion’s focus has always been on developing transformative medicines for patients with rare and ultra-rare diseases that typically affect several hundred to a few thousand patients worldwide. Like all of our medicines, ULTOMIRIS is a biologic medicine, which are very large complex molecules made up of genetically engineered proteins that are manufactured in living cells through a highly complicated process that requires significant time, expertise and precision. During this global health crisis, we have taken proactive measures that are designed to mitigate the risk of potential supply interruptions, and we strive to maintain sufficient inventory levels to continue serving current and new patients receiving our medicines for approved rare and ultra-rare indications as well as those participating in ongoing clinical trials.

We recognize that, should the role of C5 in treating severe respiratory complications of COVID-19 be demonstrated in a controlled clinical trial, there is the potential for significantly increased demand for our C5 inhibitors. We have taken steps to significantly increase future supply as part of our efforts to prepare for this and other potential scenarios that may arise so that we are ready to support access and the anticipated increased supply demand. In the meantime, Alexion will continue to monitor and manage the production of ULTOMIRIS, appropriately taking into consideration the needs of current and new patients, required inventory levels, anticipated potential supply needs related to COVID-19 and the time-intensive and complex manufacturing process to produce monoclonal antibodies while maintaining the company’s rigorous quality standards.

About ULTOMIRIS® (ravulizumab-cwvz)

ULTOMIRIS® (ravulizumab-cwvz) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. For currently approved indications, ULTOMIRIS is administered intravenously every eight weeks or every four weeks for pediatric patients less than 20 kg, following a loading dose. ULTOMIRIS is approved in the United States (U.S.), European Union (EU) and Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH) and in the U.S. for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients.

INDICATIONS & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS® (ravulizumab-cwvz) AND SOLIRIS® (eculizumab)

INDICATIONS

ULTOMIRIS and SOLIRIS are prescription medicines called monoclonal antibodies. ULTOMIRIS and SOLIRIS are used to treat adults with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH). ULTOMIRIS and SOLIRIS are also used to treat adults and children with a disease called atypical Hemolytic Uremic Syndrome (aHUS). Neither ULTOMIRIS nor SOLIRIS is for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

In addition, SOLIRIS is used to treat adults with a disease called generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. SOLIRIS is also used to treat adults with a disease called neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

It is not known if ULTOMIRIS is safe and effective in children with PNH or in children younger than one month of age in aHUS. It is also not known if SOLIRIS is safe and effective in children with PNH, gMG, or NMOSD.

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 medicines. 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 copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. 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, metabolic disorders and cardiology. Headquartered in Boston, Massachusetts, Alexion 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.

i Gralinski LE, Sheahan TP, Morrison TE, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5). doi:10.1128/mBio.01753-18.

SOURCE: Alexion Pharmaceuticals