Alexion Pharmaceuticals Inc. Receives CHMP Positive Opinions For Important Updates To The EU Label For Soliris (eculizumab)
Updated EU Label Supports Soliris Treatment of Patients with PNH Regardless of History of Transfusion
Updated EU Label Reflects New aHUS Data on Soliris Efficacy and Risks Associated with Discontinuing Treatment
LAUSANNE, Switzerland--(BUSINESS WIRE)--Alexion announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a Positive Opinion to update the therapeutic indication for Soliris® (eculizumab) in the treatment of paroxysmal nocturnal haemoglobinuria (PNH) for patients with high disease activity regardless of history of transfusion. The CHMP also issued a Positive Opinion to update the EU label for Soliris with additional data on the benefits of long-term treatment and the risks associated with treatment discontinuation in patients with atypical haemolytic uremic syndrome (aHUS). If approval is granted, updated information for the use of Soliris in both PNH and aHUS will be detailed in the Summary of Product Characteristics (SmPC) which will be published in the revised European Public Assessment Report (EPAR).
“The positive CHMP opinion is an important milestone as it underscores that complement-mediated haemolysis, and not transfusions, is the key clinical indicator of the risk for devastating and life-threatening consequences in patients with PNH,” said Carsten Thiel, Ph.D., SVP, EMEA and Asia-Pacific, Alexion. “We believe that, if approved by the European Commission, the updated EU label will better guide physicians in assessing and optimizing care for patients with this life-threatening and ultra-rare disorder.”
About the PNH Label Update
PNH is a debilitating ultra-rare blood disorder with life-threatening consequences.1-3 In patients with PNH, chronic, uncontrolled activation of complement, a component of the natural immune system, results in haemolysis (destruction of the patient's red blood cells), leading to thrombosis, organ failure and shortened survival.4-7
The CHMP based its opinion on efficacy and safety data from an observational, non-interventional international PNH Registry, which confirmed that patients with no history of transfusion who were treated with Soliris had a significant reduction in haemolysis (measured by LDH) and associated clinical symptoms, such as fatigue.
Peter Hillmen, Professor of Experimental Haematology, University of Leeds, and Honorary Consultant Haematologist at St James’s University Hospital, Leeds and Chair of the Executive Committee of the International PNH Registry, commented: “I am pleased that data from the International PNH Registry are advancing our knowledge about the underlying pathophysiology of PNH and the devastating consequences for patients. It is very good news that these data from the International PNH Registry have enabled an update to the indication for eculizumab in PNH so that patients who are at high risk of morbidities or premature mortality can benefit from eculizumab, regardless of history of transfusion.”
About the aHUS Label Update
aHUS is a genetic, ultra-rare, and life-threatening disease in which chronic uncontrolled complement activation results in complement-mediated TMA, the formation of blood clots in small blood vessels throughout the body.8,9 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.8,10
If today’s CHMP positive opinion is approved by the EC, new efficacy data will now be added to the aHUS section of the EU label specifying that longer term treatment with Soliris was associated with an increased percentage of patients who experienced clinically meaningful improvements. Importantly, when Soliris treatment was continued for more than 26 weeks, additional patients achieved complete TMA response and haematologic normalization.
In addition, Section 4.4 of the EU label will include new information on the risks associated with treatment discontinuation in patients with aHUS.11 The CHMP based its opinion on additional data from ongoing long-term follow-up studies of patients with aHUS who had previously participated in the aHUS clinical trials. These data showed that a proportion of the patients who discontinued Soliris treatment and were followed for a median period of 24 weeks experienced TMA following treatment discontinuation. Furthermore, severe TMA complications occurred in additional patients who received a reduced dosing regimen of Soliris outside of the approved dosing regimen. Serious medical complications occurred in these patients, including severe worsening of kidney function, disease-related hospitalisation and progression to end-stage renal disease requiring dialysis. These severe TMA complications occurred in patients regardless of whether they had an identified genetic mutation.
“The CHMP positive opinion recognizes the importance of sustained Soliris treatment for patients with chronic complement dysregulation and the ongoing risk of complement-mediated TMA and organ damage in patients with aHUS,” said Camille L. Bedrosian, M.D., Chief Medical Officer of Alexion. “If approved by the European Commission, these important label updates will further support the need for sustained terminal complement inhibition with Soliris, even when clinical symptoms and lab values have improved.”
Soliris is approved in nearly 50 countries as a treatment for patients with PNH and in nearly 40 countries as a treatment for patients with aHUS.
About PNH
PNH is an ultra-rare blood disorder in which chronic, uncontrolled activation of complement, a component of the normal immune system, results in haemolysis (destruction of the patient's red blood cells). PNH strikes people of all ages, with an average age of onset in the early 30s.12 Approximately 10% of all patients first develop symptoms at 21 years of age or younger.13 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.14 In the period of time before Soliris 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.12 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).15-17 In patients with thrombosis of unknown origin, PNH may be an underlying cause.12
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.8,9 Seventy-nine percent of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within three years after diagnosis despite plasma exchange or plasma infusion (PE/PI).18 Moreover, 33 to 40 percent of patients die or progress to end-stage renal disease with the first clinical manifestation of aHUS despite PE/PI.18,19 The majority of patients with aHUS who receive a kidney transplant commonly experience subsequent systemic TMA, resulting in a 90 percent transplant failure rate in these TMA patients.20
aHUS affects both children and adults. 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.18
About Soliris
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 US (2007), European Union (2007), Japan (2010) and other countries as the first and only treatment for patients with paroxysmal nocturnal haemoglobinuria (PNH), a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is indicated to reduce hemolysis.
Soliris is also approved in the US (2011), the European Union (2011), Japan (2013) and other countries as the first and only treatment for patients with atypical Haemolytic Uraemic Syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated TMA (blood clots in small vessels). For the breakthrough medical innovation in complement inhibition, Alexion and Soliris have received the pharmaceutical industry's highest honors: the 2008 Prix Galien USA Award for Best Biotechnology Product with broad implications for future biomedical research and the 2009 Prix Galien France Award in the category of Drugs for Rare Diseases.
More information including the full prescribing information on Soliris is available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdf
Important Safety Information
In Europe, the Summary of Product Characteristics (SmPC) for Soliris includes a special warning and precaution for use: Due to its mechanism of action, the use of Soliris increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). These patients might be at risk of disease by uncommon serogroups (particularly Y, W135 and X), although meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving Soliris. aHUS patients who are treated with Soliris less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients must be re-vaccinated according to current medical guidelines for vaccination use. Tetravalent vaccines against serotypes A, C, Y and W135 are strongly recommended, preferably conjugated ones. Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents.
The most common or serious adverse reactions are headache (occurred mostly in the initial phase), leukopenia and meningococcal infection. The most common (>10%) adverse reactions reported in paediatric aHUS patients were diarrhoea, vomiting, pyrexia, upper respiratory tract infection and headache. Soliris treatment should not alter anticoagulant management. Please see Summary of Product Characteristics for full prescribing information for Soliris, including all special warnings and precautions.
About Alexion
Alexion is a biopharmaceutical company focused on serving patients with severe and rare disorders through the innovation, development and commercialization of life-transforming therapeutic products. Alexion is the global leader in complement inhibition and has developed and markets Soliris® (eculizumab), a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. The treatment is currently approved in nearly 50 countries for the treatment of PNH and in nearly 40 countries for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris in additional severe and ultra-rare disorders beyond PNH and aHUS, and is developing other highly innovative biotechnology product candidates, including asfotase alfa, across multiple therapeutic areas.
Further information about Alexion can be found at: www.alexionpharma.eu.
References
1. Brodsky RA. Blood Rev. 2008;22:65-74.
2. Rachidi S, Musallam KM, Taher AT. Eur J Intern Med. 2010;21:260-267.
3. Borowitz MJ, Craig FE, DiGiuseppe JA, et al; for Clinical Cytometry Society. Cytometry Part B. 2010;78B:211-230.
4. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2005:419-427.
5. Rother RP, Bell L, Hillmen P, et al. JAMA. 2005;293:1653-1662.
6. Rother RP, Rollins SA, Mojcik CF, et al. Nat Biotechnol. 2007;25:1256-1264. [Published correction appears in Nat Biotechnol. 2007;25:1488].
7. Hillmen P, Lewis SM, Bessler M, et al. N Engl J Med. 1995;333:1253-1258.
8. Benz K, Amann K. Thrombotic microangiopathy:new insights. Curr Opin Nephrol Hypertens. 2010;19(3):242-7.
9. Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009;24:687-96.
10. Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int. 2006;70(1):16-23
11. SmPC: Soliris® (eculizumab) summary of product characteristics. Alexion Europe SAS. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdf
12. Socié G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996: 348:573-577.
13. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709.
14. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258.
15. Wang H, Chuhjo T, Yasue S, Omine M, Naka S. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood. 2002;100 (12):3897-3902.
16. Iwanga M, Furukawa K, Amenomori T, et al. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102(2):465-474.
17. Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001;115:1015-1022.
18. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676-87.
19. Caprioli J, Noris M, Brioschi S, et al. The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1269.
20. Bresin E, Daina E, Noris M, et al. Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background. Clin J Am Soc Nephrol. 2006;1:88-99.
Contacts
Alexion
Mitali Rajan, +32 2 274 0065
Associate Director, Corporate Communications EMEA
rajanm@alxn.com
Help employers find you! Check out all the jobs and post your resume.
Updated EU Label Reflects New aHUS Data on Soliris Efficacy and Risks Associated with Discontinuing Treatment
LAUSANNE, Switzerland--(BUSINESS WIRE)--Alexion announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a Positive Opinion to update the therapeutic indication for Soliris® (eculizumab) in the treatment of paroxysmal nocturnal haemoglobinuria (PNH) for patients with high disease activity regardless of history of transfusion. The CHMP also issued a Positive Opinion to update the EU label for Soliris with additional data on the benefits of long-term treatment and the risks associated with treatment discontinuation in patients with atypical haemolytic uremic syndrome (aHUS). If approval is granted, updated information for the use of Soliris in both PNH and aHUS will be detailed in the Summary of Product Characteristics (SmPC) which will be published in the revised European Public Assessment Report (EPAR).
“The positive CHMP opinion is an important milestone as it underscores that complement-mediated haemolysis, and not transfusions, is the key clinical indicator of the risk for devastating and life-threatening consequences in patients with PNH,” said Carsten Thiel, Ph.D., SVP, EMEA and Asia-Pacific, Alexion. “We believe that, if approved by the European Commission, the updated EU label will better guide physicians in assessing and optimizing care for patients with this life-threatening and ultra-rare disorder.”
About the PNH Label Update
PNH is a debilitating ultra-rare blood disorder with life-threatening consequences.1-3 In patients with PNH, chronic, uncontrolled activation of complement, a component of the natural immune system, results in haemolysis (destruction of the patient's red blood cells), leading to thrombosis, organ failure and shortened survival.4-7
The CHMP based its opinion on efficacy and safety data from an observational, non-interventional international PNH Registry, which confirmed that patients with no history of transfusion who were treated with Soliris had a significant reduction in haemolysis (measured by LDH) and associated clinical symptoms, such as fatigue.
Peter Hillmen, Professor of Experimental Haematology, University of Leeds, and Honorary Consultant Haematologist at St James’s University Hospital, Leeds and Chair of the Executive Committee of the International PNH Registry, commented: “I am pleased that data from the International PNH Registry are advancing our knowledge about the underlying pathophysiology of PNH and the devastating consequences for patients. It is very good news that these data from the International PNH Registry have enabled an update to the indication for eculizumab in PNH so that patients who are at high risk of morbidities or premature mortality can benefit from eculizumab, regardless of history of transfusion.”
About the aHUS Label Update
aHUS is a genetic, ultra-rare, and life-threatening disease in which chronic uncontrolled complement activation results in complement-mediated TMA, the formation of blood clots in small blood vessels throughout the body.8,9 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.8,10
If today’s CHMP positive opinion is approved by the EC, new efficacy data will now be added to the aHUS section of the EU label specifying that longer term treatment with Soliris was associated with an increased percentage of patients who experienced clinically meaningful improvements. Importantly, when Soliris treatment was continued for more than 26 weeks, additional patients achieved complete TMA response and haematologic normalization.
In addition, Section 4.4 of the EU label will include new information on the risks associated with treatment discontinuation in patients with aHUS.11 The CHMP based its opinion on additional data from ongoing long-term follow-up studies of patients with aHUS who had previously participated in the aHUS clinical trials. These data showed that a proportion of the patients who discontinued Soliris treatment and were followed for a median period of 24 weeks experienced TMA following treatment discontinuation. Furthermore, severe TMA complications occurred in additional patients who received a reduced dosing regimen of Soliris outside of the approved dosing regimen. Serious medical complications occurred in these patients, including severe worsening of kidney function, disease-related hospitalisation and progression to end-stage renal disease requiring dialysis. These severe TMA complications occurred in patients regardless of whether they had an identified genetic mutation.
“The CHMP positive opinion recognizes the importance of sustained Soliris treatment for patients with chronic complement dysregulation and the ongoing risk of complement-mediated TMA and organ damage in patients with aHUS,” said Camille L. Bedrosian, M.D., Chief Medical Officer of Alexion. “If approved by the European Commission, these important label updates will further support the need for sustained terminal complement inhibition with Soliris, even when clinical symptoms and lab values have improved.”
Soliris is approved in nearly 50 countries as a treatment for patients with PNH and in nearly 40 countries as a treatment for patients with aHUS.
About PNH
PNH is an ultra-rare blood disorder in which chronic, uncontrolled activation of complement, a component of the normal immune system, results in haemolysis (destruction of the patient's red blood cells). PNH strikes people of all ages, with an average age of onset in the early 30s.12 Approximately 10% of all patients first develop symptoms at 21 years of age or younger.13 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.14 In the period of time before Soliris 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.12 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).15-17 In patients with thrombosis of unknown origin, PNH may be an underlying cause.12
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.8,9 Seventy-nine percent of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within three years after diagnosis despite plasma exchange or plasma infusion (PE/PI).18 Moreover, 33 to 40 percent of patients die or progress to end-stage renal disease with the first clinical manifestation of aHUS despite PE/PI.18,19 The majority of patients with aHUS who receive a kidney transplant commonly experience subsequent systemic TMA, resulting in a 90 percent transplant failure rate in these TMA patients.20
aHUS affects both children and adults. 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.18
About Soliris
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 US (2007), European Union (2007), Japan (2010) and other countries as the first and only treatment for patients with paroxysmal nocturnal haemoglobinuria (PNH), a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is indicated to reduce hemolysis.
Soliris is also approved in the US (2011), the European Union (2011), Japan (2013) and other countries as the first and only treatment for patients with atypical Haemolytic Uraemic Syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated TMA (blood clots in small vessels). For the breakthrough medical innovation in complement inhibition, Alexion and Soliris have received the pharmaceutical industry's highest honors: the 2008 Prix Galien USA Award for Best Biotechnology Product with broad implications for future biomedical research and the 2009 Prix Galien France Award in the category of Drugs for Rare Diseases.
More information including the full prescribing information on Soliris is available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdf
Important Safety Information
In Europe, the Summary of Product Characteristics (SmPC) for Soliris includes a special warning and precaution for use: Due to its mechanism of action, the use of Soliris increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). These patients might be at risk of disease by uncommon serogroups (particularly Y, W135 and X), although meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving Soliris. aHUS patients who are treated with Soliris less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients must be re-vaccinated according to current medical guidelines for vaccination use. Tetravalent vaccines against serotypes A, C, Y and W135 are strongly recommended, preferably conjugated ones. Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents.
The most common or serious adverse reactions are headache (occurred mostly in the initial phase), leukopenia and meningococcal infection. The most common (>10%) adverse reactions reported in paediatric aHUS patients were diarrhoea, vomiting, pyrexia, upper respiratory tract infection and headache. Soliris treatment should not alter anticoagulant management. Please see Summary of Product Characteristics for full prescribing information for Soliris, including all special warnings and precautions.
About Alexion
Alexion is a biopharmaceutical company focused on serving patients with severe and rare disorders through the innovation, development and commercialization of life-transforming therapeutic products. Alexion is the global leader in complement inhibition and has developed and markets Soliris® (eculizumab), a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. The treatment is currently approved in nearly 50 countries for the treatment of PNH and in nearly 40 countries for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris in additional severe and ultra-rare disorders beyond PNH and aHUS, and is developing other highly innovative biotechnology product candidates, including asfotase alfa, across multiple therapeutic areas.
Further information about Alexion can be found at: www.alexionpharma.eu.
References
1. Brodsky RA. Blood Rev. 2008;22:65-74.
2. Rachidi S, Musallam KM, Taher AT. Eur J Intern Med. 2010;21:260-267.
3. Borowitz MJ, Craig FE, DiGiuseppe JA, et al; for Clinical Cytometry Society. Cytometry Part B. 2010;78B:211-230.
4. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2005:419-427.
5. Rother RP, Bell L, Hillmen P, et al. JAMA. 2005;293:1653-1662.
6. Rother RP, Rollins SA, Mojcik CF, et al. Nat Biotechnol. 2007;25:1256-1264. [Published correction appears in Nat Biotechnol. 2007;25:1488].
7. Hillmen P, Lewis SM, Bessler M, et al. N Engl J Med. 1995;333:1253-1258.
8. Benz K, Amann K. Thrombotic microangiopathy:new insights. Curr Opin Nephrol Hypertens. 2010;19(3):242-7.
9. Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009;24:687-96.
10. Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int. 2006;70(1):16-23
11. SmPC: Soliris® (eculizumab) summary of product characteristics. Alexion Europe SAS. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdf
12. Socié G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996: 348:573-577.
13. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709.
14. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258.
15. Wang H, Chuhjo T, Yasue S, Omine M, Naka S. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood. 2002;100 (12):3897-3902.
16. Iwanga M, Furukawa K, Amenomori T, et al. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102(2):465-474.
17. Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001;115:1015-1022.
18. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676-87.
19. Caprioli J, Noris M, Brioschi S, et al. The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1269.
20. Bresin E, Daina E, Noris M, et al. Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background. Clin J Am Soc Nephrol. 2006;1:88-99.
Contacts
Alexion
Mitali Rajan, +32 2 274 0065
Associate Director, Corporate Communications EMEA
rajanm@alxn.com
Help employers find you! Check out all the jobs and post your resume.