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46-551: Its products include eculizumab (Soliris) and ravulizumab (Ultomiris), both used to treat the rare disorders of atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH); asfotase alfa (Strensiq), used to treat hypophosphatasia ; sebelipase alfa (Kanuma), used to treat lysosomal acid lipase deficiency , and andexanet alfa (Andexxa), used to stop life threatening or uncontrollable bleeding in people who are taking rivaroxaban or apixaban . With costs that can reach as much as $ 2 million per year,

92-479: A later date, should the drug be made available at a lower price. In December 2014, the provincial government of Ontario, Canada , negotiated the price with the manufacturer, the only drug approved by Health Canada to treat atypical hemolytic uremic syndrome. People can apply for it on "compassionate grounds" "on a case-by-case basis for example individuals who have been urgently hospitalized due to an immediate life-, limb-, or organ-threatening complication." It then

138-612: A maker of rare disease treatments, in an $ 8.4 billion stock-and-cash deal. In April 2018, Alexion announced the acquisition of Wilson Therapeutics for $ 855 million. In November 2018, the company acquired Syntimmune for $ 1.2 billion, expanding its rare disease offerings. In January 2020, the company acquired Achillion Pharmaceuticals for $ 930 million, boosting its immune system disease pipeline. In July 2020, Alexion acquired Portola Pharmaceuticals , diversifying its hematology, neurology, and critical care commercial portfolio with Portola's Factor Xa inhibitor reversal agent. The following

184-468: A proposal to subsidize the drug after Alexion refused to budge on a NZ$ 670,000 (US$ 590,000) per person per year price and Pharmac's economic analysis determined the price would need to be halved before the drug was cost-effective enough to subsidize. Pharmac's decision upset many people with paroxysmal nocturnal hemoglobinuria in New Zealand, although Pharmac has not ruled out reviewing the decision at

230-445: A rare and devastating disease known as lysosomal acid lipase deficiency (LAL Deficiency). Kanuma is a recombinant form of the natural human LAL enzyme and an enzyme replacement therapy being developed for patients with LAL Deficiency. LAL Deficiency is a serious, life-threatening disease associated with early mortality and significant morbidity. LAL Deficiency is a chronic disease in which genetic mutations result in decreased activity of

276-490: A sense of tingling or numbness, blurred vision, vertigo, ringing in the ears, heart palpitations , high blood pressure, low blood pressure, vascular damage, peritonitis , constipation, upset stomach, swollen belly, itchy skin, increased sweating, blotches from small bleeds under the skin and skin redness , hives , muscle spasms, bone pain, back pain, neck pain, swollen joints, kidney damage, painful urination, spontaneous erections, general edema , chest pain, weakness, pain at

322-772: A simple blood test. Kanuma was granted orphan designation by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Ministry of Health, Labour and Welfare. Kanuma also received fast track designation by the FDA, and Breakthrough Therapy designation by the FDA for LAL Deficiency presenting in infants. The FDA accepted for review the Biologics License Application (BLA) for Kanuma, granted Synageva's request for Priority Review, and established

368-530: A story, and helped the boy's parents communicate their story to the press in order to pressure governments to reimburse the cost of the drug. Several politicians stated that the company was attempting to 'blackmail' the government, charges which Alexion denied. By 7 May 2013, an agreement had been reached for the government to reimburse the cost of the medicine beginning in July 2013. In December 2013, New Zealand's government pharmaceutical buyer Pharmac declined

414-699: A target action date of September 8, 2015 under the Prescription Drug User Fee Act (PDUFA). The EMA validated the Marketing Authorization Application (MAA) for Kanuma and granted the company's request for accelerated assessment. Synageva's other pipeline programs consisted of protein therapeutic programs for rare diseases with unmet medical need at various stages of development, including a Phase 1/2 trial with its second, first-mover program, SBC-103 for MPS IIIB. The company's third, first-mover program, SBC-105,

460-409: A value of $ 230 per share. The transaction was unanimously approved by both companies’ Boards of Directors and is valued at approximately $ 8.4 billion net of Synageva's cash (total $ 9.1 billion). This was one of the largest premiums paid to any company over $ 5 billion in market cap since 1995. In July 2008, Mr. Patel designed and initiated Synageva's lead program, Kanuma® ( sebelipase alfa ) to address

506-541: Is developed , manufactured, and marketed by Alexion Pharmaceuticals . Eculizumab is indicated for the treatment of people with paroxysmal nocturnal hemoglobinuria to reduce hemolysis; and the treatment of people with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy. Eculizumab is used to treat atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). For people with paroxysmal nocturnal hemoglobinuria, it improves quality of life and decreases

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552-569: Is Amgen Technology (Ireland) Unlimited Company. Bekemv is a biosimilar medicinal product. It is highly similar to the reference product Soliris (eculizumab), which was authorized in the EU on 20 June 2007. Data show that Bekemv has comparable quality, safety and efficacy to Soliris. Bekemv was approved for medical use in the European Union in April 2023. Epysqli was approved for medical use in

598-590: Is CAN$ 4.62 million and CAN$ 2.13 million, respectively. Based on established thresholds, the opportunity cost of funding eculizumab is 102.3 discounted QALYs per patient funded." By 2015, industry analysts and academic researchers agreed that the high price of orphan drugs, such as eculizumab, was not related to research, development, and manufacturing costs: their price is arbitrary and they have become more profitable than traditional medicines. The Brazilian universal health care system has annually provided it for its citizens. Initially patients got access to it by suing

644-515: Is an illustration of the company's mergers, acquisitions, corporate spin-offs and historical predecessors: Alexion Pharmaceuticals (Founded 1992) Proliferon Inc (Acq 2000, restructured into Alexion Antibody Technologies Inc) Enobia Pharma Corp (Acq 2011) Synageva (Acq 2015) Wilson Therapeutics (Acq 2018) Syntimmune (Acq 2018) Achillion Pharmaceuticals (Acq 2019) Portola Pharmaceuticals (Acq 2020) Eculizumab Eculizumab , sold under

690-709: The Patented Medicine Prices Review Board (PMPRB) under the Canadian Patent Act , held a preliminary hearing in Ottawa, Ontario to examine allegations. John Haslam, President and General Manager of Vaughan, Ontario-based Alexion Canada, was named as one of the respondents. Alexion charges Canada $ 700,000 per person per year, more than anywhere else in the world. Alexion denies the claim. In Canada "provincial drug plans have already negotiated secret discounts on Soliris for many of

736-727: The CFO of Honeywell , was appointed CFO, replacing Vikas Sinha. In March 2017, Alexion named Ludwig N. Hantson as its CEO. In September 2017, Alexion announced it would cut its workforce by 20% and move its headquarters to Boston, Massachusetts in mid-2018. It also announced the closure of its manufacturing facility in Smithfield, Rhode Island . In July 2020, the company agreed to pay more than $ 21 million to settle claims that it bribed government officials in Turkey and Russia to gain approval for its drugs. In July 2021, AstraZeneca acquired

782-610: The EHEC infection. In January 2014, the company paid Moderna $ 100   million for ten product options to develop rare disease treatments, including for Crigler–Najjar syndrome , using Moderna's mRNA therapeutics platform; however, the program was scrapped in January 2017 after animal trials showed that Moderna's treatment would never be safe enough for humans. In April 2015, Bell was replaced as CEO by David Hallal. In October 2015, Alexion's second drug, Strensiq ( asfotase alfa ),

828-582: The European Union in May 2023. In May 2024, eculizumab-aeeb (Bkemv) was approved for medical use in the United States. Eculizumab-aagh (Epysqli) was approved for medical use in the United States in July 2024. Eculizumab has been explored as a treatment for CD55 deficiency , also known as CHAPLE syndrome, a rare genetic disorder of the immune system. Immune activation : Dostarlimab Other: Ibalizumab Synageva Synageva BioPharma Corp.

874-526: The LAL enzyme; this leads to marked accumulation of lipids in vital organs, blood vessels, and other tissues, resulting in progressive and multi-systemic organ damage including fibrosis, cirrhosis, liver failure, accelerated atherosclerosis, cardiovascular disease, and other devastating consequences. LAL Deficiency affects patients of all ages with sudden and unpredictable clinical complications manifesting from infancy through adulthood. The disease can be diagnosed with

920-587: The UK, and $ 500,000 a year in Canada (2014). In 2021, Soliris generated US$ 1.874 billion in sales. In April and May 2013, a controversy arose in Belgium when the media revealed that the government had refused to pay for a seven-year-old boy's treatment because Soliris was too expensive. The boy's medicine cost €9,000 every two weeks. A public relations agency working for Alexion had reportedly been looking for such

966-664: The US Food and Drug Administration (FDA) in March 2007, for the treatment of paroxysmal nocturnal hemoglobinuria. Eculizumab has exclusivity rights until 2017, which protects it from competition until 2017. When the FDA approved it in September 2011, for the treatment of atypical hemolytic uremic syndrome, it designated it as an orphan drug . The FDA approval in 2011 was based on two small prospective trials of 17 people and 20 people. The European Medicines Agency approved it for

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1012-410: The brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria , atypical hemolytic uremic syndrome , generalized myasthenia gravis , and neuromyelitis optica . In people with paroxysmal nocturnal hemoglobinuria, it reduces both the destruction of red blood cells and need for blood transfusion , but does not appear to affect

1058-668: The breakdown of red blood cells in the bloodstream (intravascular hemolysis) in people with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. The most frequently reported adverse reactions for people with paroxysmal nocturnal hemoglobinuria include headache, nasopharyngitis (common cold), back pain and nausea The most frequently reported adverse reactions for people with atypical hemolytic uremic syndrome include headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, swelling of lower legs or hands, nausea, urinary tract infections and fever Eculizumab (Soliris)

1104-805: The company's direction to focus on products for the treatment of devastating, rare diseases. This represented a substantial shift in the original company's business strategy of developing bio-similar drugs using its novel egg white (EW) protein production technology. The company's proprietary technology produces proteins by recombinant DNA technology in egg white (EW) using a transgenic Gallus expression system. The proteins are then purified using conventional recombinant protein chromatographic methods. The EW system can consistently express proteins that contain glycan structures, predominantly GlcNAc- and mannose-terminated N-linked glycan structures, as well as mannose-6-phosphate (M6P) glycans, which are specifically recognized and internalized via receptors into key target cells. With

1150-426: The company. In September 2000, Alexion acquired Proliferon, a development-stage biopharmaceutical firm, for $ 41 million in stock. The company was renamed Alexion Antibody Technologies. In December 2011, Alexion acquired Montreal-based Enobia Pharma, the developer of asfotase alfa , a drug used to treat the genetic disorder hypophosphatasia , for as much as $ 1.08 billion. In June 2015, Alexion acquired Synageva ,

1196-513: The complement protein C5. It is an immunoglobulin G-kappa (IgGκ) consisting of human constant regions and murine complementarity-determining regions grafted onto human framework light and heavy chain variable regions. The compound contains two 448-amino acid heavy chains and two 214-amino acid light chains, and has a molecular weight of approximately 148 kilodaltons (kDa). Eculizumab was approved by

1242-437: The complement-mediated events that are characteristic of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. The metabolism of eculizumab is thought to occur via lysosomal enzymes that cleave the antibody to generate small peptides and amino acids. The volume of distribution of eculizumab in humans approximates that of plasma . Eculizumab is a recombinant humanized monoclonal antibody against

1288-573: The destruction of red blood cells as well as severe cases of blood clots forming in small blood vessels . Headaches are very common adverse effects, occurring in more than 10% of people who take the drug. Common adverse effects (occurring in between 1% and 10% of people who take the drug) include infections (pneumonia, upper respiratory tract infection, colds, and urinary tract infection), loss of white blood cells , loss of red blood cells , anaphylactic reaction , hypersensitivity reaction , loss of appetite, mood changes like depression and anxiety,

1334-567: The drugs manufactured by Alexion are some of the most expensive drugs worldwide. Alexion Pharmaceuticals was founded in 1992 at Science Park in New Haven, Connecticut by Steven Squinto and Leonard Bell, a physician at Yale New Haven Hospital and assistant professor of medicine and pathology at Yale School of Medicine . In 2000, Alexion moved its headquarters from New Haven to Cheshire, Connecticut . Alexion received U.S. Food and Drug Administration (FDA) approval for Soliris in 2007. It

1380-540: The government and demanding the right for treatment. In 2016 it was the medication that gave the biggest cost to the system by the judicial way, accounting to 625 million reais (about US$ 178 million at the time) to treat 364 patients, but it was second when counting all the system regular medications, the biggest cost being sofosbuvir . Brazil's supreme court ruled in April 2018 to break the patent of Soliris in Brazil, enabling it to be produced locally. In December 2018 it

1426-490: The increased risk of meningococcal infections, meningococcal vaccination is recommended at least 2 weeks prior to receiving eculizumab, unless the risks of delaying eculizumab therapy outweigh the risk of developing a meningococcal infection, in which case the meningococcal vaccine should be administered as soon as possible. Both a serogroup A, C, W, Y conjugate meningococcal vaccine and a serogroup B meningococcal vaccine are recommended for people receiving eculizumab. Receiving

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1472-402: The infusion site, and elevated transaminases . Eculizumab specifically binds to the terminal complement component 5 , or C5, which acts at a late stage in the complement cascade. When activated, C5 is involved in activating host cells, thereby attracting pro-inflammatory immune cells, while also destroying cells by triggering pore formation. By inhibiting the complement cascade at this point,

1518-828: The need for blood transfusions but does not appear to affect the risk of death. It does not appear to change the risk of blood clots, myelodysplastic syndrome , acute myelogenous leukemia , or aplastic anemia . Eculizumab is also used to treat neuromyelitis optica spectrum disorder in adults who are anti-aquaporin-4 (AQP4) antibody positive. Eculizumab carries a boxed warning for the risk of meningococcal infections caused by Neisseria meningitidis . Eculizumab inhibits terminal complement activation and therefore makes people vulnerable to infection with encapsulated organisms. Life-threatening and fatal meningococcal infections have occurred in people who received eculizumab. People receiving eculizumab have up to 2,000 times greater risk of developing invasive meningococcal disease . Due to

1564-525: The normal, disease-preventing functions of proximal complement system are largely preserved, while the properties of C5 that promote inflammation and cell destruction are impeded. Eculizumab inhibits the cleavage of C5 by the C5 convertase into C5a , a potent anaphylatoxin with prothrombotic and proinflammatory properties, and C5b, which then forms the terminal complement complex C5b-9 which also has prothrombotic and proinflammatory effects. Both C5a and C5b-9 cause

1610-527: The patients they cover." As of 2015, while eculizumab used for paroxysmal nocturnal hemoglobinuria was associated with 1.13 additional life years and 2.45 quality of life years QALYs, there has been a high incremental cost (CAN$ 5.24 million) and a substantial opportunity cost . A 2014 Canadian study calculated the cost per life-year-gained with treatment as CAN$ 4.62 million (US$ 4,571,564) and cost per quality-adjusted-life-year as CAN$ 2.13 million (US$ 2,112,398)."The incremental cost per life year and per QALY gained

1656-406: The recommended vaccinations may not prevent all meningococcal infections, especially from nongroupable N. meningiditis. In 2017, it became clear that eculizumab has caused invasive meningococcal disease despite vaccination, because it interferes with the ability of antimeningococcal antibodies to protect against invasive disease. The drug's labels also carry warnings of severe anemia arising from

1702-476: The results of the PREVENT trial. A 2014 study showed that Eculizumab may provide substantive benefits to people with paroxysmal nocturnal hemoglobinuria in terms of life expectancy and quality of life but at a high incremental cost. In 2010, Alexion priced Soliris as the most expensive drug in the world, at approximately US$ 409,500 a year in the United States (2010), €430,000 per year for ongoing treatment in

1748-420: The risk of death. Eculizumab was the first medication approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion . It is a humanized monoclonal antibody functioning as a terminal complement inhibitor. It binds to the complement C5 protein and inhibits activation of the complement system, a part of the body's immune system. This binding prevents

1794-557: The support from a dedicated and experienced team, Synageva went public on the NASDAQ Global Market in November 2011 by completing a reverse merger with Trimeris, Inc. Synageva later relocated its corporate headquarters to Lexington, Massachusetts. On May 6, 2015, Alexion Pharmaceuticals ( Nasdaq :  ALXN ) and Synageva announced that they entered into a definitive agreement in which Alexion would acquire Synageva for

1840-533: The treatment of paroxysmal nocturnal hemoglobinuria in June 2007, and in November 2011, for the treatment of atypical hemolytic uremic syndrome. Health Canada approved it in 2009, to treat paroxysmal nocturnal hemoglobinuria and in 2013, as the only drug to treat atypical hemolytic uremic syndrome. Eculizumab was approved by the FDA for the treatment of adults with neuromyelitis optica spectrum disorder who are anti-aquaporin-4 (AQP4) antibody positive in 2019, based on

1886-524: Was a publicly listed biopharmaceutical company headquartered in Lexington, Massachusetts dedicated to discovering, developing and delivering medicines for patients with rare diseases and high unmet medical needs. The company had manufacturing and laboratory locations in Lexington and Holden, Massachusetts, Bogart and Athens Georgia, as well as offices in a variety of locations around the world. Synageva

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1932-492: Was already "funded by the Ontario government for the treatment of another rare illness, paroxysmal nocturnal hemoglobinuria (PNH), through a bulk-buy deal reached by the provincial premiers in 2011." In February 2015, Canada's drug-price regulator took the rare step of calling a hearing into Soliris, accusing Alexion of exceeding the permissible price cap under the ""Highest International Price Comparison"" (HIPC). In June 2015,

1978-623: Was approved by the Food and Drug Administration . It is used to treat hypophosphatasia , a rare metabolic disorder. In 2016, the company became a member of the Pharmaceutical Research and Manufacturers of America (PhRMA). Alexion moved its headquarters back to New Haven following the completion of New Haven's Downtown Crossing project in February 2016. In December 2016, David Brennan became interim CEO. David Anderson, formerly

2024-571: Was formed when Sanj K. Patel (formerly an executive at Genzyme Corporation, Cambridge, Massachusetts) was approached in early 2008 by Baker Bros. Investments to be the CEO of privately-held Avigenics, Inc. in Athens, Georgia, a company initially formed by Dr. Robert Ivarie of the University of Georgia. Upon joining AviGenics in June 2008, Mr. Patel created the vision and strategy for Synageva and changed

2070-665: Was incorporated in the public health care system. A biosimilar branded Elizaria is available in Russia. In February 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Bekemv, intended for the treatment of adults and children in paroxysmal nocturnal hemoglobinuria. The applicant for this medicinal product

2116-457: Was initially approved to treat paroxysmal nocturnal hemoglobinuria , a rare blood disorder. In June 2010, there was an outbreak of hemolytic–uremic syndrome caused by shigatoxigenic and verotoxigenic Escherichia coli (EHEC) in Germany. Soliris was tested as a treatment option because of its effectiveness in treating atypical hemolytic uremic syndrome , an illness similar to that caused by

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