Alexion Pharmaceuticals
Annual Report 2012

Plain-text annual report

A l e x i o n P h a r m a c e u t i c a l s , I n c . 2 0 1 2 A n n u a l R e p o r t Alexion Pharmaceuticals, Inc. 352 Knotter Drive, Cheshire, CT 06410, USA Alexion Pharma International Sàrl Avenue du Tribunal Fédéral 34, 1005, Lausanne, Switzerland Alexion Pharma G.K. Ebisu Prime Square Tower, Tokyo 150-0012, Japan Alexion Pharmaceuticals Australasia Pty Limited 117 Old Pittwater Road, Brookvale NSW Australia, 2100 Alexion Pharma Mexico S de RL de CV Paseo de los Tamarindos 90 Torre 1 Piso 14, Col. Bosques de la Lomas, CP 05120 D.F. Mexico www.alexionpharma.com 2012 Annual Report Alexion Milestones: 1992 – 2012 1992 Alexion commences operations in New Haven, CT 1996 Initial Public Offering on NASDAQ under ticker symbol ALXN 2008 Soliris receives the 2008 Prix Galien USA Award for “Best Biotechnology Product with Broad Implications for Future Biomedical Research” 1998 First in-human clinical trial with eculizumab commences 2000 Alexion relocates to new corporate headquarters in Cheshire, CT 2002 Researchers in Leeds, England, commence a pilot study with eculizumab in patients with PNH (paroxysmal nocturnal hemoglobinuria), a severe, life-threatening and ultra-rare hematologic disorder 2009 Soliris receives the Prix Galien France Award for “Drugs for Rare Diseases” 2009 Alexion’s Rhode Island Manufacturing Facility receives European Commission approval to supply Soliris 2010 Alexion’s Rhode Island Manufacturing Facility receives FDA approval to supply Soliris 2011 US FDA approves Soliris as the first and only treatment for adult and pediatric patients with aHUS 2004 The New England Journal of Medicine publishes positive results from the pilot study with eculizumab in 11 patients with PNH 2011 European Commission approves Soliris as the first and only treatment for adult and pediatric patients with aHUS 2004 TRIUMPH, the first pivotal Phase 3 study in patients with PNH, commences 2005 Alexion Europe SAS is established in Paris, France in anticipation of creating access to Soliris® (eculizumab) for patients with PNH in Europe 2006 The New England Journal of Medicine publishes strongly positive clinical data from the TRIUMPH PNH study 2007 US FDA approves Soliris as the first and only treatment for patients with PNH 2007 European Commission approves Soliris as the first and only treatment for patients with PNH 2008 Independent physicians in Germany and France first use Soliris as a treatment for patients with atypical hemolytic uremic syndrome (aHUS), a severe, life- threatening and ultra-rare disorder of uncontrolled complement activation Today, as the global Alexion team pursues our mission to develop and deliver life-transforming therapies for patients with severe and life-threatening ultra-rare disorders, we continue to: • Bring Soliris to more patients with PNH in more countries around the world • Advance the launch of Soliris for patients with aHUS in the US and Europe • Accelerate development of the most robust research pipeline in our history, with five compounds being investigated in nine severe, ultra-rare disorders • Build our global organization, now with over 1,500 employees working in Company facilities in 35 countries, to serve more patients worldwide Alexion will establish its new world headquarters in New Haven, CT in 2015. As Alexion continues to grow, our new headquarters will provide a global center for our research initiatives and business operations around the world as we accelerate our efforts to develop and deliver life-transforming therapies for patients suffering with severe and life-threatening ultra-rare disorders. 1 4 5 7 9 13 8 12 16 19 2 3 6 20 21 22 10 11 14 15 17 18 In 2012 our employees around the world celebrated Alexion’s 20th Anniversary. Founded in 1992, Alexion has grown into a global biopharmaceutical company with over 1,500 dedicated colleagues and operations in place to serve patients in nearly 50 countries. 1. Barcelona, Spain 7. Stockholm, Sweden 13. Toronto, Canada 19. Smithfield, RI, USA 2. Cheshire, CT, USA 8. Shanghai, China 14. Buenos Aires, Argentina 20. Paris, France 3. Brussels, Belgium 9. Cambridge, MA, USA 15. Mexico City, Mexico 21. Mumbai, India 4. Milan, Italy 10. Montréal, Canada 16. Munich, Germany 22. Sydney, Australia 5. Bogotá, Colombia 11. Moscow, Russia 17. Lausanne, Switzerland 6. Istanbul, Turkey 12. Tokyo, Japan 18. Washington, DC, USA Annual Shareholders Meeting To be held on May 6, 2013 5:00 p.m. The Study at Yale 1157 Chapel Street New Haven, CT 06511 tel 203.503.3900 Other Information Corporate Headquarters Alexion Pharmaceuticals, Inc. 352 Knotter Drive Cheshire, CT 06410 tel 203.272.2596 fax 203.271.8190 Transfer Agent and Registrar Computershare Trust Company, N.A. 250 Royall Street Canton, MA 02021 Investor Relations Rx Communications 445 Park Avenue, 10th Floor New York, NY 10022 tel 917.322.2569 fax 917.322.2570 Legal Counsel Ropes & Gray LLP Boston, MA Independent Auditors PricewaterhouseCoopers LLP Hartford, CT Trading Symbol Listing for Alexion Pharmaceuticals, Inc. is found on the NASDAQ stock market under the symbol ALXN. alexionpharma.com Shareholder Information Directors Max Link, PhD1,4 Chairman of the Board Former Chairman of the Board and CEO, Centerpulse AG Former CEO, Corange Former Chairman of the Board and CEO, Sandoz Pharma, Ltd. Leonard Bell, MD Chief Executive Officer William R. Keller2,3 Vice Chairman of Shanghai Association of Foreign Investment Enterprises Senior Consultant of Shanghai Foreign Investment Development Board Former General Manager, Roche China Ltd. Joseph A. Madri, PhD, MD2,4 Professor of Pathology, Yale University School of Medicine Larry L. Mathis1,3 Former President and CEO, The Methodist Hospital System R. Douglas Norby1,3 Former Senior Vice President, Chief Financial Officer, Tessera Technologies, Inc. Alvin S. Parven2,3 President, ASP Associates Former Vice President, Aetna Health Plans Andreas Rummelt, PhD1,4 CEO, InterPharmaLink AG Former Group Head, Quality Assurance and Technical Operations, Novartis Former Member of Executive Committee, Novartis Former CEO, Sandoz AG Ann M. Veneman2,3 Former Executive Director of UNICEF Former Secretary of US Department of Agriculture Senior Management Leonard Bell, MD Chief Executive Officer Stephen P. Squinto, PhD Executive Vice President, Head of Research and Development Vikas Sinha, MBA, CA, CPA Executive Vice President, Chief Financial Officer David L. Hallal Executive Vice President, Chief Commercial Officer Clare Carmichael Senior Vice President, Chief Human Resources Officer John B. Moriarty, Jr., JD Senior Vice President, General Counsel Frank Wright Senior Vice President, President, Alexion Pharma International Sàrl Camille L. Bedrosian, MD Senior Vice President, Chief Medical Officer Thomas Bock, MD, MBA Senior Vice President, Global Medical Affairs M. Stacy Hooks, PhD Senior Vice President, Technical Operations Claude Nicaise, MD Senior Vice President, Strategic Product Development and Global Regulatory Affairs Heidi L. Wagner, JD Senior Vice President, Global Government Affairs Claus Weisemann, PhD Senior Vice President, Corporate Quality and Compliance James P. Bilotta, MBA Vice President, Chief Information Officer Henric Bjarke Vice President, Global Metabolic Franchise Daniel N. Caron, MS Vice President, Site Operations and Engineering Sven Ante (Bill) Lundberg, MD Vice President, Head of Translational Medicine Margaret M. Olinger, MBA Vice President, Global Hematology Franchise Jeremy P. Springhorn, PhD Vice President, Corporate Strategy and Business Development Jeroen van Beek, PhD Vice President, Global Nephrology Franchise 1 Member of the Audit Committee 2 Member of the Compensation Committee 3 Member of the Nominating and Corporate Governance Committee © 2013 Alexion Pharmaceuticals, Inc. Alexion®, Alexion Logo® and Soliris® are trademarks of 4 Member of the Pharmaceutical Compliance and Quality Committee Alexion Pharmaceuticals, Inc. Alexion will establish its new world headquarters in New Haven, CT in 2015. As Alexion continues to grow, our new headquarters will provide a global center for our research initiatives and business operations around the world as we accelerate our efforts to develop and deliver life-transforming therapies for patients suffering with severe and life-threatening ultra-rare disorders. 1 4 5 7 9 13 8 12 16 19 2 3 6 20 21 22 10 11 14 15 17 18 In 2012 our employees around the world celebrated Alexion’s 20th Anniversary. Founded in 1992, Alexion has grown into a global biopharmaceutical company with over 1,500 dedicated colleagues and operations in place to serve patients in nearly 50 countries. 1. Barcelona, Spain 7. Stockholm, Sweden 13. Toronto, Canada 19. Smithfield, RI, USA 2. Cheshire, CT, USA 8. Shanghai, China 14. Buenos Aires, Argentina 20. Paris, France 3. Brussels, Belgium 9. Cambridge, MA, USA 15. Mexico City, Mexico 21. Mumbai, India 4. Milan, Italy 10. Montréal, Canada 16. Munich, Germany 22. Sydney, Australia 5. Bogotá, Colombia 11. Moscow, Russia 17. Lausanne, Switzerland 6. Istanbul, Turkey 12. Tokyo, Japan 18. Washington, DC, USA Annual Shareholders Meeting To be held on May 6, 2013 5:00 p.m. The Study at Yale 1157 Chapel Street New Haven, CT 06511 tel 203.503.3900 Other Information Corporate Headquarters Alexion Pharmaceuticals, Inc. 352 Knotter Drive Cheshire, CT 06410 tel 203.272.2596 fax 203.271.8190 Transfer Agent and Registrar Computershare Trust Company, N.A. 250 Royall Street Canton, MA 02021 Investor Relations Rx Communications 445 Park Avenue, 10th Floor New York, NY 10022 tel 917.322.2569 fax 917.322.2570 Legal Counsel Ropes & Gray LLP Boston, MA Independent Auditors PricewaterhouseCoopers LLP Hartford, CT Trading Symbol Listing for Alexion Pharmaceuticals, Inc. is found on the NASDAQ stock market under the symbol ALXN. alexionpharma.com Shareholder Information Directors Max Link, PhD1,4 Chairman of the Board Former Chairman of the Board and CEO, Centerpulse AG Former CEO, Corange Former Chairman of the Board and CEO, Sandoz Pharma, Ltd. Leonard Bell, MD Chief Executive Officer William R. Keller2,3 Vice Chairman of Shanghai Association of Foreign Investment Enterprises Senior Consultant of Shanghai Foreign Investment Development Board Former General Manager, Roche China Ltd. Joseph A. Madri, PhD, MD2,4 Professor of Pathology, Yale University School of Medicine Larry L. Mathis1,3 Former President and CEO, The Methodist Hospital System R. Douglas Norby1,3 Former Senior Vice President, Chief Financial Officer, Tessera Technologies, Inc. Alvin S. Parven2,3 President, ASP Associates Former Vice President, Aetna Health Plans Andreas Rummelt, PhD1,4 CEO, InterPharmaLink AG Former Group Head, Quality Assurance and Technical Operations, Novartis Former Member of Executive Committee, Novartis Former CEO, Sandoz AG Ann M. Veneman2,3 Former Executive Director of UNICEF Former Secretary of US Department of Agriculture Senior Management Leonard Bell, MD Chief Executive Officer Stephen P. Squinto, PhD Executive Vice President, Head of Research and Development Vikas Sinha, MBA, CA, CPA Executive Vice President, Chief Financial Officer David L. Hallal Executive Vice President, Chief Commercial Officer Clare Carmichael Senior Vice President, Chief Human Resources Officer John B. Moriarty, Jr., JD Senior Vice President, General Counsel Frank Wright Senior Vice President, President, Alexion Pharma International Sàrl Camille L. Bedrosian, MD Senior Vice President, Chief Medical Officer Thomas Bock, MD, MBA Senior Vice President, Global Medical Affairs M. Stacy Hooks, PhD Senior Vice President, Technical Operations Claude Nicaise, MD Senior Vice President, Strategic Product Development and Global Regulatory Affairs Heidi L. Wagner, JD Senior Vice President, Global Government Affairs Claus Weisemann, PhD Senior Vice President, Corporate Quality and Compliance James P. Bilotta, MBA Vice President, Chief Information Officer Henric Bjarke Vice President, Global Metabolic Franchise Daniel N. Caron, MS Vice President, Site Operations and Engineering Sven Ante (Bill) Lundberg, MD Vice President, Head of Translational Medicine Margaret M. Olinger, MBA Vice President, Global Hematology Franchise Jeremy P. Springhorn, PhD Vice President, Corporate Strategy and Business Development Jeroen van Beek, PhD Vice President, Global Nephrology Franchise 1 Member of the Audit Committee 2 Member of the Compensation Committee 3 Member of the Nominating and Corporate Governance Committee © 2013 Alexion Pharmaceuticals, Inc. Alexion®, Alexion Logo® and Soliris® are trademarks of 4 Member of the Pharmaceutical Compliance and Quality Committee Alexion Pharmaceuticals, Inc. A l e x i o n P h a r m a c e u t i c a l s , I n c . 2 0 1 2 A n n u a l R e p o r t Alexion Pharmaceuticals, Inc. 352 Knotter Drive, Cheshire, CT 06410, USA Alexion Pharma International Sàrl Avenue du Tribunal Fédéral 34, 1005, Lausanne, Switzerland Alexion Pharma G.K. Ebisu Prime Square Tower, Tokyo 150-0012, Japan Alexion Pharmaceuticals Australasia Pty Limited 117 Old Pittwater Road, Brookvale NSW Australia, 2100 Alexion Pharma Mexico S de RL de CV Paseo de los Tamarindos 90 Torre 1 Piso 14, Col. Bosques de la Lomas, CP 05120 D.F. Mexico www.alexionpharma.com 2012 Annual Report Alexion Milestones: 1992 – 2012 1992 Alexion commences operations in New Haven, CT 1996 Initial Public Offering on NASDAQ under ticker symbol ALXN 2008 Soliris receives the 2008 Prix Galien USA Award for “Best Biotechnology Product with Broad Implications for Future Biomedical Research” 1998 First in-human clinical trial with eculizumab commences 2000 Alexion relocates to new corporate headquarters in Cheshire, CT 2002 Researchers in Leeds, England, commence a pilot study with eculizumab in patients with PNH (paroxysmal nocturnal hemoglobinuria), a severe, life-threatening and ultra-rare hematologic disorder 2009 Soliris receives the Prix Galien France Award for “Drugs for Rare Diseases” 2009 Alexion’s Rhode Island Manufacturing Facility receives European Commission approval to supply Soliris 2010 Alexion’s Rhode Island Manufacturing Facility receives FDA approval to supply Soliris 2011 US FDA approves Soliris as the first and only treatment for adult and pediatric patients with aHUS 2004 The New England Journal of Medicine publishes positive results from the pilot study with eculizumab in 11 patients with PNH 2011 European Commission approves Soliris as the first and only treatment for adult and pediatric patients with aHUS 2004 TRIUMPH, the first pivotal Phase 3 study in patients with PNH, commences 2005 Alexion Europe SAS is established in Paris, France in anticipation of creating access to Soliris® (eculizumab) for patients with PNH in Europe 2006 The New England Journal of Medicine publishes strongly positive clinical data from the TRIUMPH PNH study 2007 US FDA approves Soliris as the first and only treatment for patients with PNH 2007 European Commission approves Soliris as the first and only treatment for patients with PNH 2008 Independent physicians in Germany and France first use Soliris as a treatment for patients with atypical hemolytic uremic syndrome (aHUS), a severe, life- threatening and ultra-rare disorder of uncontrolled complement activation Today, as the global Alexion team pursues our mission to develop and deliver life-transforming therapies for patients with severe and life-threatening ultra-rare disorders, we continue to: • Bring Soliris to more patients with PNH in more countries around the world • Advance the launch of Soliris for patients with aHUS in the US and Europe • Accelerate development of the most robust research pipeline in our history, with five compounds being investigated in nine severe, ultra-rare disorders • Build our global organization, now with over 1,500 employees working in Company facilities in 35 countries, to serve more patients worldwide 2012 Accomplishments January The first patient with atypical hemolytic uremic syndrome (aHUS) is enrolled in the global aHUS Registry September Forbes ranks Alexion #2 on its annual list of “The World’s Most Innovative Companies” February Alexion completes acquisition of Enobia Pharma Corp., including asfotase alfa, an investigational treatment for patients with hypophosphatasia (HPP), an ultra-rare, life- threatening, genetic metabolic disease for which there are no approved treatment options October Data from an investigator-initiated Phase 2 study of eculizumab (Soliris) in patients with severe relapsing Neuromyelitis Optica (NMO) presented at the American Neurological Association (ANA) annual meeting show eculizumab significantly reduced frequency of attacks in patients March The New England Journal of Medicine publishes data from a Phase 2 study of asfotase alfa in patients with HPP; data show 90 percent of patients treated with asfotase alfa achieved substantial skeletal healing at 24 weeks, with improvements in cognitive development and motor and pulmonary function Data from a Phase 2 study of asfotase alfa in adolescents and adults with HPP presented at the American College of Medical Genetics (ACMG) annual meeting show that all patients who were treated with asfotase alfa had an objective response to therapy as indicated by a reduction in tissue non-specific alkaline phosphatase (TNSALP) substrates. In addition, treated patients showed increase in distance in the six-minute walk test (6MWT) May Alexion is added to the S&P 500 Index of leading global companies June Researchers present data at the European Hematology Association (EHA) meeting underscoring the critical need for testing patients at high risk for PNH New data, also presented at EHA, show that the majority of patients with aHUS experienced systemic multi-organ complications prior to treatment, underscoring the risk for sudden and potentially fatal systemic complications of aHUS Alexion announces plans to relocate its global headquarters to New Haven, CT, US in 2015 November Investigators present two-year data at the American Society of Nephrology (ASN) annual meeting showing the long-term benefits of chronic Soliris therapy in patients with aHUS, including continued inhibition of complement- mediated thrombotic microangiopathy (TMA) and improvement in renal function Final 28-week data from a single-arm eculizumab trial in patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS), also presented at ASN, show a rapid and sustained improvement in TMA and reversal of organ damage with eculizumab treatment December Researchers present data at the American Society of Hematology (ASH) annual meeting showing that the significant clinical benefits and long-term safety were sustained over 10 years in PNH patients treated with Soliris Two-year data demonstrating long-term benefits of chronic Soliris therapy in patients with aHUS are also presented at ASH Early 2013 Alexion submits a supplemental Biologics License Application (sBLA) to regulatory authorities in Japan for Soliris as a treatment for patients with aHUS Patient enrollment for a clinical trial of asfotase alfa in HPP begins in Japan Alexion expands its kidney transplant program to include a third clinical study in transplant patients at elevated risk for delayed graft function (DGF); investigator-initiated study in DGF is under way Forward-looking statements: This Annual Report contains forward-looking statements, all of which involve certain assumptions, risks, and uncertainties that are beyond Alexion’s control and could cause our actual results to differ materially from the statements described. Forward-looking statements involve significant risks and uncertainties, including those more fully described in our Form 10-K contained within this Annual Report and in the most recent periodic reports on Form 10-Q filed by Alexion with the US Securities and Exchange Commission, and actual results may vary materially. Alexion does not undertake any duty to update any forward-looking statements contained in this Annual Report as a result of new information, future events, or otherwise. Alexion Pharmaceuticals Twenty Years of Innovation 1 “When I was diagnosed with PNH, I was 24 years old, engaged to be married and part of an NCAA championship team in college wrestling. I was devastated when I read that one-third of people with PNH only live for five years from their diagnosis and terrified that I would not be able to have a future with my fiancée. Today, I am taking Soliris, happily married and thrilled to welcome our four-month-old daughter into our lives.” — Joe E. Patient with PNH receiving Soliris To Our Shareholders: In 2012, as Alexion celebrated its 20th anniversary as a • In our development programs for new indications with biotechnology innovator, we again strongly advanced our eculizumab – advancing our clinical programs in life- mission to develop and deliver life-transforming therapies for threatening, ultra-rare disorders in multiple therapeutic patients with severe and life-threatening disorders that are areas, including nephrology, neurology and transplant also ultra-rare. Our achievements during 2012 spanned our key commercial and clinical growth initiatives: • In our development programs with highly innovative therapeutics beyond eculizumab – accelerating the clinical • In PNH (paroxysmal nocturnal hemoglobinuria) – bringing development of asfotase alfa as the first treatment for Soliris® (eculizumab) to more patients with PNH in our patients with hypophosphatasia (HPP), and progressing the core countries of the United States, Western Europe and development of our other highly innovative therapeutics Japan, as well as to growing numbers of new PNH patients including our cPMP replacement therapy for patients in additional countries • In aHUS (atypical hemolytic uremic syndrome) – introducing Soliris in the United States as the first and only treatment for patients with aHUS, and preparing for our Soliris launches in aHUS in the major European countries • Beyond PNH and aHUS – advancing our broad development pipeline, with lead clinical programs now investigating five highly innovative compounds, including eculizumab, as treatments for patients with nine additional severe and life-threatening ultra-rare disorders with molybdenum cofactor deficiency (MoCD) type A; ALXN1102/1103, our alternative complement pathway inhibitor; and ALXN1007, a novel anti-inflammatory antibody Serving More Patients with PNH Worldwide Even as we drive forward with these wide-ranging growth initiatives, our focus on serving patients with PNH has never been greater – especially since, on a global basis, the majority of PNH patients have not yet received an accurate diagnosis, let alone commenced appropriate treatment. PNH is a debilitating and life-threatening ultra-rare blood disorder characterized by • And overall, achieving significant growth across our uncontrolled complement activation leading to complement- business while maintaining strong financial discipline to mediated hemolysis (destruction of red blood cells). Before achieve increasing operational leverage Soliris, approximately one-third of patients with PNH did not survive more than five years from the time of diagnosis. With 2013: Reaching Milestones Across the availability of Soliris, the outlook for patients has changed Our Growth Initiatives With a global operations platform that now serves patients in nearly 50 countries – and the most robust pipeline of innovative therapeutic candidates in our history – we are on track to reach an unprecedented number of key milestones across our commercial and clinical initiatives in 2013. Our objectives for the year include: • In our approved indications for Soliris – reaching more patients in countries where commercial operations are already in place, and accelerating our market entries in new countries. In PNH and aHUS alike, our steadfast objective is that every patient who can benefit from Soliris will have access to Soliris dramatically: In the initial PNH registration trials, 100 percent of patients had an objective response to Soliris, and long-term data published by independent investigators from patients treated with Soliris for up to eight years showed improved survival rates similar to normal healthy individuals matched for their age and gender. In 2012, data presented at the American Society of Hematology (ASH) annual meeting further demonstrated long- term efficacy and safety in PNH patients treated with Soliris over the course of 10 years. The growing body of data regarding both PNH and the clinical benefits of Soliris is vital for patients. As with many ultra-rare disorders – even those that are severe and for which there is an effective, approved therapy – patients with PNH often suffer Alexion Pharmaceuticals Twenty Years of Innovation 3 “After months of being misdiagnosed, I was finally told I had aHUS. With this news came a year of debilitating dialysis, extreme nausea and exhaustion, and the loss of vision in one eye due to a retinal blood clot. In 2012, my hematologist started me on Soliris. I am thankful to be able to work again and live like other people my age.” — Erica S. Patient with aHUS receiving Soliris needlessly because there may be little awareness amongst the marketing authorization for Soliris as the first and only medical community of how to recognize or treat their disorder. approved treatment for patients with aHUS at the end of In 2013, the seventh year of the global introduction of Soliris, 2011. Both approvals resulted in strong and broad labels that we will build on the medical evidence as we continue to expand include pediatric and adult patients with aHUS. In 2012, the our PNH disease awareness programs and diagnostic initiatives. first full year in which Soliris was available to patients in the Since 2007, these programs have been vital to educating the US, we were able to rapidly meet the urgent medical needs medical community on which patients are at greatest likelihood of patients presenting with aHUS. of having PNH, the best ways to arrive at an accurate diagnosis, and the most effective treatment options. We enter 2013 with a foundation in place for a strong global launch in aHUS. The devastating course of this disorder, together In 2012, as in the past, we served substantial numbers of with the life-transforming benefits of Soliris treatment, provides new patients with PNH in each quarter across our longest a solid underpinning for rapid diagnosis, reimbursement and established territories in the United States, Western Europe treatment of aHUS patients around the world. We are pleased and Japan. Importantly, we also began to serve initial to have built strong support among key opinion leaders who patients in Turkey, Brazil and Russia as we implemented recognize the life-transforming impact that Soliris is having disease awareness programs and diagnostic initiatives. In on patients with aHUS. Our efforts are further supported 2013, we will increase our penetration in all countries in by a growing body of clinical data demonstrating the long- which we are currently active. Additionally, we look forward term benefits of Soliris for patients with aHUS. This includes to significant opportunities to serve patients in parts of Latin two-year data from the prospective Phase 2 trials that were America, including Argentina, Colombia and Mexico, as well presented at both the American Society of Nephrology (ASN) as additional countries including Korea. and ASH annual meetings in 2012, which showed continued Bringing the Unprecedented Hope of Soliris to Additionally, an established group of European aHUS clinical Initial Patients with aHUS experts published a paper supporting Soliris as first-line therapy As we continue our mission to transform the lives of patients in patients confirmed to have aHUS. improvement in hematologic and renal function with Soliris. with PNH, we have now also begun to transform the lives of patients with aHUS, a chronic, ultra-rare and life-threatening disease in which a genetic deficiency in one or more complement regulatory genes causes chronic uncontrolled complement activation. The lifelong uncontrolled complement activation in aHUS progressively damages vital organs, leading to stroke, heart attack, kidney failure and premature death. Prior to the availability of Soliris for the treatment of aHUS, 65 percent of patients required dialysis, had permanent kidney damage or died within the first year of diagnosis despite receiving plasma exchange or plasma infusion (PE/PI). As in PNH, 100 percent of patients in the aHUS registration trials had an objective response to Soliris. Following strongly positive results in our prospective clinical trials in aHUS, the FDA and European Commission granted In the US, a broad range of aHUS patients are being diagnosed and treated with Soliris, including both children and adults, and those with and without a history of receiving plasma exchange. Patients with aHUS are also being treated by multiple specialties and in both hospital and outpatient practice settings. As is also our experience in PNH, we are seeing positive results from our diagnostic initiatives and disease awareness programs for aHUS. For example, an aHUS diagnostic pathway has been introduced to hematologists and nephrologists with positive impact, which we believe will facilitate the more rapid diagnosis of patients with aHUS. Importantly, patients with aHUS in the United States are gaining rapid access to Soliris through broad reimbursement. Alexion Pharmaceuticals Twenty Years of Innovation 5 Research Pipeline: Lead Programs Preclinical Phase I Phase II Phase III Market Soliris® (eculizumab) Paroxysmal Nocturnal Hemoglobinuria Atypical Hemolytic Uremic Syndrome Shiga-toxin E. coli-related Hemolytic Uremic Syndrome Kidney Transplant (Acute Humoral Rejection) Kidney Transplant (Delayed Graft Function)* Severe and Relapsing Neuromyelitis Optica* Severe Myasthenia Gravis Asfotase Alfa Hypophosphatasia cPMP Replacement Therapy Molybdenum Cofactor Deficiency Type A ALXN1102/1103 Inflammatory Disorders ALXN1007 Inflammatory Disorders Pipeline Key Hematology Inflammatory Disorders Metabolic Nephrology Neurology * Investigator-Initiated Trial 6 Alexion Pharmaceuticals 2012 Annual Report In Europe, we are now serving aHUS patients in Germany disorders for which there are no approved or effective and initial patients in other countries are also receiving therapies – disorders that are simultaneously the rarest, in Soliris on a named-patient basis or through local funding which only very few patients are affected. We now have nine authorities. We are also on track to complete the such R&D programs under way, each of which is expected to reimbursement processes for aHUS in most of the larger reach one or more important milestones in 2013. Western European countries and to commence individual country launches during 2013. While our European teams Investigating the Potential of Eculizumab (Soliris) are planning for their individual country launches, we have Beyond PNH and aHUS also recently submitted our supplemental Biologics License Application (sBLA) for aHUS in Japan, an important step for Our five lead development programs with eculizumab are focused on severe and ultra-rare complement-mediated subsequent access to Soliris for Japanese patients. We look disorders beyond PNH and aHUS. forward to serving an increasing number of patients with aHUS around the world throughout 2013 and beyond. Serving More Patients with More Severe and Ultra-Rare Disorders • Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC- HUS) is a devastating and life-threatening ultra-rare disease that develops in a subset of patients who become infected with enterohemorrhagic E. coli (EHEC). Final 28-week data from our single-arm eculizumab STEC-HUS trial, which was Beyond our current commercial initiatives in our approved initiated in Germany during the historic EHEC outbreak in Soliris indications, we are keenly focused on the need to mid-2011, were presented at the ASN meeting in November develop additional highly innovative uses for the breakthrough 2012. The data showed that the full clinical study cohort of complement-inhibition technology of eculizumab. We are 198 patients had a rapid and sustained improvement in TMA equally driven by the need to develop new therapeutic agents, and reversal of organ damage with eculizumab treatment. both within and beyond complement-mediated diseases. Importantly, we are also obtaining and analyzing additional The expertise we have gained from our experience with Soliris informs all of our pipeline development decisions. We are among the very few companies to have successfully developed and commercialized a high-value ultra-orphan therapy, bringing it through clinical trials and regulatory approval, and then commercializing it successfully in multiple indications around the world on our own. Through this experience, we have learned how to work with regulators to develop approval pathways and trial protocols in disease settings in which control data from an exploratory matched-control analysis of patients with severe STEC-HUS receiving eculizumab versus other patients who received only best supportive care. The preliminary findings from this analysis showed that eculizumab treatment was associated with consistently higher rates of improvement in renal and neurological function at 8 weeks and 28 weeks, when compared with supportive care only. We believe the additional control data will strengthen our anticipated regulatory submission. there are no clinical precedents. We have also gained valuable • Kidney Transplant is another area in which complement experience in enrolling trial sites around the world to recruit can play a significant role. We currently have two patients with the rarest and most severe disorders, as well development programs under way: as in conducting successful disease education programs to significantly raise awareness of a devastating and ultra-rare disorder and the most effective ways to diagnose and treat it. • Acute Humoral Rejection (AHR) – we are currently enrolling patients at elevated risk of AHR, or antibody mediated rejection, in a multinational living-donor kidney transplant To best employ these skills on behalf of patients, we trial and a separate multinational deceased-donor kidney now focus only on the most severe and life-threatening transplant trial Alexion Pharmaceuticals Twenty Years of Innovation 7 “Evie was diagnosed with hypophosphatasia, or HPP, when she was just a few weeks old and we were told that 50% of patients with severe HPP did not survive past one year of age. Needless to say, we were devastated. Fortunately, we were given the opportunity to participate in a clinical trial with asfotase alfa. Today, Evie is still in the trial and enjoys music classes and playing with her sister Lyla.” — Lindsey E. Mother of child with HPP • Delayed Graft Function (DGF) – we recently expanded our newborn patients with HPP die within one year, and there kidney transplant program to include patients at elevated are no effective treatment options. Clinical trial results from risk for DGF as we sponsored an investigator-initiated study a single-arm study published in the New England Journal • Neuromyelitis Optica (NMO) is a devastating, life- threatening, ultra-rare neurological disease in which uncontrolled complement activation causes damage to the spinal cord and optic nerve, leading to paralysis, respiratory failure, blindness and premature death. Positive data from an investigator-initiated Phase 2 single-arm study of eculizumab in patients with severe relapsing NMO presented at the 2012 American Neurological Association annual meeting showed eculizumab significantly reduced frequency of attacks in patients with severe relapsing NMO. Following recent meetings with regulators in the US and Europe, we are accelerating this program and expect to of Medicine in 2012 showed a dramatic clinical benefit of asfotase alfa and an objective response in 100 percent of study participants. Alexion is currently accelerating the clinical development program for children with HPP, with our objective to file for pediatric registration in the US and Europe. In addition, we are completing the current clinical development program for adults with HPP. Beyond the US and Europe, we have started a registration trial in Japan. During 2012, we also completed an important phase of the process development work in the asfotase alfa manufacturing program to support our clinical studies and eventual commercialization. initiate a single multinational registration trial. • cPMP replacement is an investigational therapy for • Myasthenia Gravis (MG) is a debilitating and sometimes life-threatening neurological disorder in which uncontrolled complement activation leads to destruction and inflammation at the neuromuscular junction, resulting in severe muscle weakness. Following encouraging results from a Phase 2 study in severe and refractory MG, we have started regulatory discussions and are planning to initiate our next study. Beyond Eculizumab: Highly Innovative Therapeutics to Treat Ultra-Rare Disorders Our development programs beyond Soliris are guided by what we know well and do well, applying our proven skills exclusively to patients suffering from severe and life-threatening illnesses in ultra-rare settings. As with our eculizumab programs, we focus only on therapeutic candidates with strong potential to transform patients’ lives – not just provide an incremental benefit. • Asfotase alfa is a highly innovative, late-stage biologic being developed for patients with hypophosphatasia (HPP), an inherited and life-threatening ultra-rare metabolic disorder the treatment of patients with molybdenum cofactor deficiency (MoCD) type A, a severe, ultra-rare and genetic metabolic disorder that is fatal in newborns. Early case studies with cPMP have shown highly encouraging results in individual patients, and we are driven by the potential for cPMP to change the grim outcomes that these infants currently face. We are now planning to initiate the first prospective clinical studies with cPMP. • ALXN1102/ALXN1103 are the intravenous and subcutaneous versions, respectively, of our novel alternative pathway complement inhibitor, which we are in the early stages of investigating as treatments for severe and ultra-rare inflammatory disorders. We are progressing through our current Phase 1 clinical trial, with the objective to develop subsequent clinical studies with this novel complement inhibitor. • ALXN1007, a novel anti-inflammatory antibody designed to target severe and ultra-rare inflammatory disorders, is a product of our antibody discovery technologies. We recently completed a single-dose Phase 1 clinical trial in 56 patients and are planning to discuss a multi-dose study that leads to progressive damage to multiple vital organs, with regulators. including destruction and deformity of bones. One-half of Alexion Pharmaceuticals Twenty Years of Innovation 9 From left: Stephen P. Squinto, PhD, Executive Vice President and Head of Research and Development; John B. Moriarty, Jr., JD, Senior Vice President and General Counsel; Leonard Bell, MD, Chief Executive Officer; David L. Hallal, Executive Vice President and Chief Commercial Officer; Clare Carmichael, Senior Vice President and Chief Human Resources Officer; Vikas Sinha, MBA, CA, CPA, Executive Vice President and Chief Financial Officer; Frank Wright, Senior Vice President and President, Alexion Pharma International Sàrl. “Our accomplishments in 2012 position us for continued strong growth in 2013, which we expect will be a pivotal year of milestones across both our commercial operations and development pipeline. Our goal is to continue serving more patients with more disorders worldwide in the decade ahead.” — Leonard Bell, MD Chief Executive Officer Continued Strong Financial Performance 2012 was another year of sustained growth in revenues and profitability for Alexion. For the full year, we recorded sales of $1.134 billion, an increase of 45% compared to 2011. By maintaining fiscal discipline as we have grown our global operations to now serve patients in nearly 50 countries, we achieved a 60% increase in non-GAAP net income to $425.2 million in 2012. In 2012 we reported robust year- on-year revenue growth across all of our countries. Revenues in the US increased 52% during the year, reflecting continued growth in PNH and the first full year of the aHUS launch. This strong growth in our largest market six years after the initial launch supports the robust Soliris® Net Product Sales 8 % 15 % 34 % 43 % 2011 $783,431 In 2012, we welcomed two new leaders to Alexion’s executive team: John Moriarty joined Alexion as Senior Vice President and General Counsel, and Frank Wright joined us as Senior Vice President and Head of Alexion Pharma International Sàrl. Both are seasoned executives who will play key roles as we grow our multi-product portfolio in an increasing 14 % number of countries. 14 % 35 % To support our continued growth, we have also announced the relocation of our global headquarters from Cheshire, CT to New 37 % Haven, CT in 2015. Our new headquarters 2012 $1,134,114 United States Europe Asia-Pacific (primarily Japan) Other will provide a global center for our research initiatives and business operations around the world to accelerate our efforts to serve more patients with severe and life-threatening ultra-rare disorders. Looking Ahead in 2013 Our history of innovation since 1992 will serve as the guide for future growth. We long-term growth potential of the Soliris franchise. Revenues are inspired by the number of lives we have been able to in Europe increased 27% on a constant currency basis more transform through the introduction of Soliris for PNH and than five years following our initial EU approval. Likewise, we aHUS, and we will employ our expanding global presence achieved strong growth of 40% in our PNH operations in Asia- and skills to deliver additional breakthrough therapies for Pacific, largely related to Japan. The growing momentum of patients with devastating and ultra-rare disorders who our global expansion is further indicated by the 141% year-on- currently suffer without hope. We are thankful for all those year growth we experienced across our newer markets. Taken who make our work possible: our employees, Board of together, the diverse operations that we are building around Directors and shareholders, as well as healthcare authorities the world provide us with a foundation for long-term growth around the world. Most of all, we thank the patients, in PNH, aHUS and future indications. families and physicians we serve around the world as we strive to reach new levels of innovation on their behalf. Strengthening Our Human Capital and Resources Today, Alexion has more than 1,500 employees working in Company facilities in 35 countries. We are grateful for the passion and commitment of our talented and dedicated employees as we work together to serve patients with ultra- Leonard Bell, MD rare diseases. Chief Executive Officer April 2013 Alexion Pharmaceuticals Twenty Years of Innovation 11 Selected GAAP Financial Results (In thousands, except per share data) Year Ended December 31, 2012 2011 2010 Net product sales Cost of sales $ 1,134,114 72,837 $ 783,431 93,140 $ 540,957 64,437 Operating expenses: Research and development Selling, general and administrative Acquisition-related costs Impairment of intangible asset Amortization of purchased intangible assets Total operating expenses Operating income Other expense Income before income taxes Income tax provision Net income 222,732 384,678 22,812 26,300 417 137,421 308,176 13,486 — 382 98,394 226,766 722 — — 656,939 459,465 325,882 404,338 6,772 397,566 142,744 230,826 1,158 229,668 54,353 150,638 1,627 149,011 51,981 $ 254,822 $ 175,315 $ 97,030 Earnings per common share — diluted Shares used in computing earnings per share — diluted $ 1.28 198,501 $ 0.91 191,806 $ 0.52 186,074 As of December 31, 2012 2011 2010 Consolidated Balance Sheet Data: Cash, cash equivalents and marketable securities $ 989,501 $ 540,865 $ 361,605 Trade accounts receivable, net Inventories Property, plant and equipment, net Goodwill and intangible assets, net Deferred tax assets Other assets Total assets Accounts payable and accrued expenses Deferred revenue Contingent consideration Long-term debt Other liabilities Total liabilities 295,598 94,521 165,629 900,323 40,040 127,948 244,288 81,386 165,852 171,243 123,000 68,117 168,732 62,165 162,240 44,100 174,212 38,983 2,613,560 1,394,751 1,012,037 271,275 31,266 141,670 149,000 49,499 642,710 199,653 17,905 18,120 — 24,581 260,259 123,056 2,896 — — 26,349 152,301 Total stockholders’ equity 1,970,850 1,134,492 859,736 Total liabilities and stockholders’ equity 2,613,560 1,394,751 1,012,037 12 Alexion Pharmaceuticals 2012 Annual Report Alexion will establish its new world headquarters in New Haven, CT in 2015. As Alexion continues to grow, our new headquarters will provide a global center for our research initiatives and business operations around the world as we accelerate our efforts to develop and deliver life-transforming therapies for patients suffering with severe and life-threatening ultra-rare disorders. 1 4 5 7 9 13 8 12 16 19 2 3 6 20 21 22 10 11 14 15 17 18 In 2012 our employees around the world celebrated Alexion’s 20th Anniversary. Founded in 1992, Alexion has grown into a global biopharmaceutical company with over 1,500 dedicated colleagues and operations in place to serve patients in nearly 50 countries. 1. Barcelona, Spain 7. Stockholm, Sweden 13. Toronto, Canada 19. Smithfield, RI, USA 2. Cheshire, CT, USA 8. Shanghai, China 14. Buenos Aires, Argentina 20. Paris, France 3. Brussels, Belgium 9. Cambridge, MA, USA 15. Mexico City, Mexico 21. Mumbai, India 4. Milan, Italy 10. Montréal, Canada 16. Munich, Germany 22. Sydney, Australia 5. Bogotá, Colombia 11. Moscow, Russia 17. Lausanne, Switzerland 6. Istanbul, Turkey 12. Tokyo, Japan 18. Washington, DC, USA Annual Shareholders Meeting To be held on May 6, 2013 5:00 p.m. The Study at Yale 1157 Chapel Street New Haven, CT 06511 tel 203.503.3900 Other Information Corporate Headquarters Alexion Pharmaceuticals, Inc. 352 Knotter Drive Cheshire, CT 06410 tel 203.272.2596 fax 203.271.8190 Transfer Agent and Registrar Computershare Trust Company, N.A. 250 Royall Street Canton, MA 02021 Investor Relations Rx Communications 445 Park Avenue, 10th Floor New York, NY 10022 tel 917.322.2569 fax 917.322.2570 Legal Counsel Ropes & Gray LLP Boston, MA Independent Auditors PricewaterhouseCoopers LLP Hartford, CT Trading Symbol Listing for Alexion Pharmaceuticals, Inc. is found on the NASDAQ stock market under the symbol ALXN. alexionpharma.com Shareholder Information Directors Max Link, PhD1,4 Chairman of the Board Former Chairman of the Board and CEO, Centerpulse AG Former CEO, Corange Former Chairman of the Board and CEO, Sandoz Pharma, Ltd. Leonard Bell, MD Chief Executive Officer William R. Keller2,3 Vice Chairman of Shanghai Association of Foreign Investment Enterprises Senior Consultant of Shanghai Foreign Investment Development Board Former General Manager, Roche China Ltd. Joseph A. Madri, PhD, MD2,4 Professor of Pathology, Yale University School of Medicine Larry L. Mathis1,3 Former President and CEO, The Methodist Hospital System R. Douglas Norby1,3 Former Senior Vice President, Chief Financial Officer, Tessera Technologies, Inc. Alvin S. Parven2,3 President, ASP Associates Former Vice President, Aetna Health Plans Andreas Rummelt, PhD1,4 CEO, InterPharmaLink AG Former Group Head, Quality Assurance and Technical Operations, Novartis Former Member of Executive Committee, Novartis Former CEO, Sandoz AG Ann M. Veneman2,3 Former Executive Director of UNICEF Former Secretary of US Department of Agriculture Senior Management Leonard Bell, MD Chief Executive Officer Stephen P. Squinto, PhD Executive Vice President, Head of Research and Development Vikas Sinha, MBA, CA, CPA Executive Vice President, Chief Financial Officer David L. Hallal Executive Vice President, Chief Commercial Officer Clare Carmichael Senior Vice President, Chief Human Resources Officer John B. Moriarty, Jr., JD Senior Vice President, General Counsel Frank Wright Senior Vice President, President, Alexion Pharma International Sàrl Camille L. Bedrosian, MD Senior Vice President, Chief Medical Officer Thomas Bock, MD, MBA Senior Vice President, Global Medical Affairs M. Stacy Hooks, PhD Senior Vice President, Technical Operations Claude Nicaise, MD Senior Vice President, Strategic Product Development and Global Regulatory Affairs Heidi L. Wagner, JD Senior Vice President, Global Government Affairs Claus Weisemann, PhD Senior Vice President, Corporate Quality and Compliance James P. Bilotta, MBA Vice President, Chief Information Officer Henric Bjarke Vice President, Global Metabolic Franchise Daniel N. Caron, MS Vice President, Site Operations and Engineering Sven Ante (Bill) Lundberg, MD Vice President, Head of Translational Medicine Margaret M. Olinger, MBA Vice President, Global Hematology Franchise Jeremy P. Springhorn, PhD Vice President, Corporate Strategy and Business Development Jeroen van Beek, PhD Vice President, Global Nephrology Franchise 1 Member of the Audit Committee 2 Member of the Compensation Committee 3 Member of the Nominating and Corporate Governance Committee © 2013 Alexion Pharmaceuticals, Inc. Alexion®, Alexion Logo® and Soliris® are trademarks of 4 Member of the Pharmaceutical Compliance and Quality Committee Alexion Pharmaceuticals, Inc. A l e x i o n P h a r m a c e u t i c a l s , I n c . 2 0 1 2 A n n u a l R e p o r t Alexion Pharmaceuticals, Inc. 352 Knotter Drive, Cheshire, CT 06410, USA Alexion Pharma International Sàrl Avenue du Tribunal Fédéral 34, 1005, Lausanne, Switzerland Alexion Pharma G.K. Ebisu Prime Square Tower, Tokyo 150-0012, Japan Alexion Pharmaceuticals Australasia Pty Limited 117 Old Pittwater Road, Brookvale NSW Australia, 2100 Alexion Pharma Mexico S de RL de CV Paseo de los Tamarindos 90 Torre 1 Piso 14, Col. Bosques de la Lomas, CP 05120 D.F. Mexico www.alexionpharma.com 2012 Annual Report Alexion Milestones: 1992 – 2012 1992 Alexion commences operations in New Haven, CT 1996 Initial Public Offering on NASDAQ under ticker symbol ALXN 2008 Soliris receives the 2008 Prix Galien USA Award for “Best Biotechnology Product with Broad Implications for Future Biomedical Research” 1998 First in-human clinical trial with eculizumab commences 2000 Alexion relocates to new corporate headquarters in Cheshire, CT 2002 Researchers in Leeds, England, commence a pilot study with eculizumab in patients with PNH (paroxysmal nocturnal hemoglobinuria), a severe, life-threatening and ultra-rare hematologic disorder 2009 Soliris receives the Prix Galien France Award for “Drugs for Rare Diseases” 2009 Alexion’s Rhode Island Manufacturing Facility receives European Commission approval to supply Soliris 2010 Alexion’s Rhode Island Manufacturing Facility receives FDA approval to supply Soliris 2011 US FDA approves Soliris as the first and only treatment for adult and pediatric patients with aHUS 2004 The New England Journal of Medicine publishes positive results from the pilot study with eculizumab in 11 patients with PNH 2011 European Commission approves Soliris as the first and only treatment for adult and pediatric patients with aHUS 2004 TRIUMPH, the first pivotal Phase 3 study in patients with PNH, commences 2005 Alexion Europe SAS is established in Paris, France in anticipation of creating access to Soliris® (eculizumab) for patients with PNH in Europe 2006 The New England Journal of Medicine publishes strongly positive clinical data from the TRIUMPH PNH study 2007 US FDA approves Soliris as the first and only treatment for patients with PNH 2007 European Commission approves Soliris as the first and only treatment for patients with PNH 2008 Independent physicians in Germany and France first use Soliris as a treatment for patients with atypical hemolytic uremic syndrome (aHUS), a severe, life- threatening and ultra-rare disorder of uncontrolled complement activation Today, as the global Alexion team pursues our mission to develop and deliver life-transforming therapies for patients with severe and life-threatening ultra-rare disorders, we continue to: • Bring Soliris to more patients with PNH in more countries around the world • Advance the launch of Soliris for patients with aHUS in the US and Europe • Accelerate development of the most robust research pipeline in our history, with five compounds being investigated in nine severe, ultra-rare disorders • Build our global organization, now with over 1,500 employees working in Company facilities in 35 countries, to serve more patients worldwide 

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