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For more information,  you may email Bill Biermann at  BBiermann@Premier-ks.com   or visit www.Atypicalhus.org  or visit   www.Atypicalhus.net

 

 

Atypical HUS

Atypical HUS (Hemolytic Uremic Syndrome) is not caused by an external agent (such as a bacteria, virus etc). Instead, some sort of internal chain of events sets the HUS off, and the syndrome becomes active.


The latest discoveries in Human Genetics have  allowed Medical professionels to classify Atypical HUS into 3 major categories.  The categories are a) Pneumococcus 2) Genetic (Complement system) and c)  Others.  It is believed that a majority of the cases are genetic in origin.

     As of October 07, there were 4 genes associated with this disorder.  They are Factor H, Factor I, Factor B and MCP.  The first three genes are responsible for producing proteins that originate in the liver.  The fourth, MCP, is not systhesized in the liver, but rather is a protecitve coating that lines the kidneys. 

     All four factors cause a problem in the complement system, which ends up damaging the endothelium.  However, the first three proteins are 'free floating", and therefore the origin can be thought of as originating in the complement system. To be more specific, a dysfunctional level of a factor H, I or B protein fails to shut off the complement system (part of the immune system).  This process is not evident until a "trigger" mechanism such as infection, cold, flu sets off a cascasding chain of events.  Complement cascade then proceeds to injure microscopic blood vessels, (Microangeaopathic Hemolytic anemia), and thrombosis (clots) occur.   The kidney is the organ that seems especially suseptible to these problems. 

There are also a variety of other unknown causes, (ie ideopathic Atypical HUs). 

In either case, Atypical HUS patients have many of the the same symptons as Typical HUS Patients.
However, there are quite a number of differences. While the Typical form of the disease may start off more severe, the Atypical form is subject to longer lingering effects, and is much more likely to become a chronic problem. Recurrance is much more common with the Atypical form of the disease.

Frequency of Atypical HUS

Atypical HUS is quite rare.  The number of cases in the world is unknown.  It does not seem to have any barriers geographically.  In the United States, there is believed to be between 300 - 600 cases. Most cases occur in young children, although some adults may suddenly get hit with the disease. The disease is not contagious, therefore, there is no required reporting. 

Breaking News as of Sept 22, 2011

Soliris® (eculizumab) Approved by FDA for All Patients with Atypical Hemolytic Uremic Syndrome (aHUS)

- First and Only Approved Treatment for Children and Adults Suffering with aHUS, an Ultra-Rare, Life-Threatening Disease – - Conference Call Scheduled for Monday, September 26, 2011 at 10:00am Eastern - CHESHIRE, Conn.--(BUSINESS WIRE)-- Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced that the U.S. Food and Drug Administration (FDA) has approved Soliris® (eculizumab) for the treatment of all pediatric and adult patients with atypical hemolytic uremic syndrome (aHUS). aHUS is an ultra-rare, life-threatening, genetic disease that progressively damages vital organs, leading to stroke, heart attack, kidney failure and death.1 The morbidity and premature mortality in aHUS is caused by chronic uncontrolled activation of the complement system, resulting in the formation of blood clots in small blood vessels throughout the body, known as thrombotic microangiopathy or TMA.2,3 Despite current supportive care, more than half of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within 1 year of diagnosis.4 Soliris, a first-in-class terminal complement inhibitor, specifically targets uncontrolled complement activation, and is indicated for the treatment of patients with aHUS to inhibit complement-mediated TMA. The new aHUS indication has been granted under the FDA’s accelerated approval process based on two prospective studies in a total of 37 adult and adolescent patients, together with a retrospective study that included 19 pediatric patients. The effectiveness of Soliris in aHUS is based on the effects on TMA and renal function in these completed trials. Prospective clinical trials in additional patients are ongoing to confirm the benefit of Soliris in patients with aHUS. The ongoing prospective clinical trials are designed with the same endpoints as the completed trials. Soliris is not indicated for the treatment of patients with Shiga toxin E coli-related hemolytic uremic syndrome (STEC-HUS).5 Alexion is currently evaluating the safety and efficacy of eculizumab for the treatment of patients with STEC-HUS. “Soliris directly targets uncontrolled complement activation, the underlying cause of the progressive organ failure and shortened life span of patients with aHUS, an extremely rare and devastating disease,” said Larry Greenbaum, M.D., Ph.D., Director of Pediatric Nephrology at Emory University and Children’s Healthcare of Atlanta. “The FDA approval of Soliris in aHUS marks the most important advance that has been made for patients and families with this disease.” “In clinical trials, Soliris markedly decreased the TMA process, which is responsible for thrombosis, renal impairment, seizures, and angina in patients with aHUS,” said Craig B. Langman, M.D., The Isaac A Abt MD Professor of Kidney Diseases, Head of Kidney Diseases, Feinberg School of Medicine, Northwestern University. “This is the first time I have seen a therapy with such a dramatic benefit, including restored kidney function. Soliris can change the course of aHUS and make a remarkable difference for patients with this life-threatening disease.” Earlier today, Alexion announced that the European Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending that the therapeutic indication for Soliris be extended to include the treatment of pediatric and adult patients with aHUS. Based on the CHMP's positive recommendation, a final decision from the European Commission is expected in approximately two months. Soliris has been previously approved in the US (2007), European Union (2007), Japan (2010) and in other territories, for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating, ultra-rare and life-threatening blood disorder. “Soliris is the treatment advance that the aHUS community has been seeking for decades,” said Bill Biermann, Co-founder of the Foundation for Children with Atypical HUS. “Today’s approval is a breakthrough for patients and their families who have been waiting for a treatment for this extremely rare genetic disease. Greater awareness and understanding, along with an effective new therapy, has the potential to accelerate diagnosis and improve management of aHUS, sparing patients and families the devastation many of us have endured.” Soliris in aHUS Clinical Data The FDA approval of Soliris in aHUS is based on data from two prospective pivotal Phase 2 open-label clinical trials in adolescent and adult patients with aHUS, and a third retrospective study in children, adolescents, and adults with aHUS. The studies included patients with or without an identified complement regulatory factor genetic mutation. Patients had an ADAMTS13 activity level greater than 5%. The three studies included: (i) 17 patients who were resistant or intolerant to plasma exchange/infusion, (ii) 20 patients who were receiving chronic plasma exchange/infusion, and (iii) 19 pediatric patients (ages 2 months to 17 years) who received Soliris outside of prospective clinical trials and with or without prior plasma exchange/infusion. All patients treated with Soliris demonstrated reduction in terminal complement activity. All studies met their key clinical objectives. Final data from the prospective studies were presented at the 16th Congress of the European Hematology Association (EHA) in June 2011.6,7
  • In the first study6, Soliris-treated patients demonstrated a significant improvement in platelet count from baseline through week 26 of 73×109/L (p=0.0001). Hematologic normalization was observed in 13 of 17 Soliris-treated patients (76%). TMA event-free status was achieved by 15 of 17 Soliris-treated patients (87%). Patients treated with Soliris also showed a statistically significant reduction in the TMA intervention rate, improved renal function, reduction in dialysis, and improved quality of life.
  • In the second study7, the primary endpoint of TMA event-free status was achieved by 16 of 20 Soliris-treated patients (80%). Hematologic normalization was achieved in 18 of 20 Soliris-treated patients (90%). Patients treated with Soliris also achieved statistically significant reduction in the TMA intervention rate, maintained or improved kidney function, and improved quality of life. No patient required new dialysis with Soliris.
  • In the third study, as described in the new Soliris product label, platelet count was normalized in 17 of 19 pediatric patients (89%) treated with Soliris. Patients treated with Soliris also achieved a reduction in the TMA intervention rate. No patient required new dialysis during treatment with Soliris. The safety and effectiveness of Soliris for the treatment of aHUS appeared similar in pediatric and adult patients.
Soliris was well tolerated in these clinical studies. The most frequently reported adverse events were hypertension, upper respiratory tract infection, and diarrhea. “Today’s approval brings life-transforming hope to children and adults suffering with aHUS,” said Leonard Bell, M.D., Chief Executive Officer of Alexion. “In a disease defined by uncontrolled complement activation, it is important to note that in our clinical studies, every patient with aHUS had an objective reduction in complement activity with Soliris therapy. We are pleased that this important treatment is now available for patients with aHUS and their families.” Conference Call/Web Cast Information: Alexion will host a conference call/webcast that is scheduled for Monday, September 26, 2011 at 10:00 a.m., Eastern Time to discuss the FDA approval. In addition, a brief financial update will be provided. To participate in this call, dial 877-719-9801 (USA) or 719-325-4806 (International), confirmation code 4412871 shortly before 10:00 a.m., Eastern Time. A replay of the call will be available for a limited period following the call, beginning at 2:00 p.m. Eastern Time. The replay number is 888-203-1112 (USA) or 719-457-0820 (International), confirmation code 4412871. The audio webcast can be accessed at www.alexionpharma.com. About aHUS aHUS is a chronic, ultra-rare, and life-threatening disease in which a genetic deficiency in one or more complement regulatory genes causes life-long uncontrolled complement activation, resulting in complement-mediated thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body.1,2 Permanent, uncontrolled complement activation in aHUS causes a life-long risk for TMA, which leads to sudden, catastrophic, and life-threatening damage to the kidney, brain, heart, and other vital organs, and premature death. 2,3 More than half of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within 1 year of diagnosis.4 Patients with aHUS who receive a kidney transplant commonly experience subsequent systemic TMA, resulting in a 90% transplant failure rate.8 aHUS affects both children and adults. In a large group of aHUS patients, 60% were first diagnosed at younger than 18 years of age.9 Complement-mediated TMA also causes reduction in platelet count (thrombocytopenia) and red blood cell destruction (hemolysis). While mutations have been identified in at least ten different complement regulatory genes, mutations are not identified in 30-50% of patients with a confirmed diagnosis of aHUS.9 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 U.S., European Union, Japan and other countries as the first treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is also approved in the U.S. as the first treatment for patients with atypical Hemolytic Uremic Syndrome (aHUS), a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated thrombotic microangiopathy (blood clots in small vessels). Alexion's breakthrough approach in complement inhibition has 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 on Soliris is available at www.soliris.net Important Safety Information Soliris is generally well tolerated in patients with PNH and aHUS. In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), and back pain. Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were hypertension, upper respiratory tract infection, and diarrhea. The U.S. product label for Soliris also includes a boxed warning: "Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections (5.1) for additional guidance on the management of meningococcal infection.) Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program (5.2). Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-soliris (1-888-765-4747).” Please see full prescribing information for Soliris, including boxed WARNING regarding risk of serious meningococcal infection. About Alexion Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on serving patients with severe and ultra-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) as a treatment for patients with PNH and aHUS, two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. Soliris is currently approved in more than 35 countries for the treatment of PNH, and in the United States for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris and is pursuing development of other innovative biotechnology product candidates in early stages of development. This press release and further information about Alexion Pharmaceuticals, Inc. can be found at: www.alexionpharma.com. Safe Harbor Statement This news release contains forward-looking statements, including statements related to anticipated clinical development, regulatory and commercial milestones and potential health and medical benefits of Soliris® (eculizumab) for the potential treatment of patients with aHUS. Forward-looking statements are subject to factors that may cause Alexion's results and plans to differ from those expected, including for example, decisions of regulatory authorities regarding marketing approval or material limitations on the marketing of Soliris for its current or potential new indications, and a variety of other risks set forth from time to time in Alexion's filings with the Securities and Exchange Commission, including but not limited to the risks discussed in Alexion's Quarterly Report on Form 10-Q for the period ended June 30, 2011, and in Alexion's other filings with the Securities and Exchange Commission. Alexion does not intend to update any of these forward-looking statements to reflect events or circumstances after the date hereof, except when a duty arises under law. [ALXN-G] References 1. Noris M, Remuzzi G: Atypical hemolytic-uremic syndrome. N Engl J Med 2009 361:1676-87 2. Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin Nephrol Hypertens 2010 May;19(3):242-7 3. Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int 2006 Jul;70(1):16-23. 4. Caprioli J, Noris M, Brioschi S, et al; for the International Registry of Recurrent and Familial HUS/TTP. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1279. 5. Soliris (eculizumab) full prescribing information. 2011. Cheshire, CT: Alexion Pharmaceuticals 6. Loirat C, Babu S, Furman R, Sheerin N, Cohen D, Gaber O, et al. Eculizumab Efficacy and Safety in Patients With Atypical Hemolytic Uremic Syndrome (aHUS) Resistant to Plasma Exchange/Infusion [poster]. Presented at the 16th Congress of European Hematology Association (EHA), 2011. London, UK. 7. Loirat C, Muus P, Legendre C, Douglas K, Hourmant M, Delmas Y, et al. A Phase II Study of Eculizumab in Patients With Atypical Hemolytic Uremic Syndrome Receiving Chronic Plasma Exchange/Infusion [poster].. Presented at the 16th Congress of European Hematology Association (EHA), 2011. London, UK. 8. Bresin E, Daina E, Noris M, et al; International Registry of Recurrent and Familial HUS/TTP. Outcome of renal transplantation in patients with non–Shiga toxin-associated hemolytic uremic syndrome: prognostic signifi cance of genetic background. Clin J Am Soc Nephrol. 2006;1:88-99. 9. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844-1859.ContactsAlexion Pharmaceuticals, Inc.
Irving Adler, 203-271-8210
Sr. Director, Corporate Communications
or
Media:
Makovsky + Company
Mark Marmur, 212-508-9670
or
Investors:
Rx Communications
Rhonda Chiger, 917-322-2569
 Source: Alexion Pharmaceuticals, Inc.

News update as of June, 2010

Early Clinical Experience and Basic Science Support Further Investigation of Soliris® (eculizumab) for the Treatment of Patients with Thrombotic Microangiopathy

Case Reports and Basic Science Presented at International Conference on HUS, PNH and MPGN

CHESHIRE, Conn., Jun 15, 2010 (BUSINESS WIRE) -- Researchers reported today that Soliris(R) (eculizumab), a first-in-class terminal complement inhibitor developed by Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN), may provide clinical benefits to patients with thrombotic microangiopathy (TMA) resulting from uncontrolled complement activation. TMA, the formation of blood clots in capillaries and small arteries, can lead to life-threatening damage in multiple organs including kidney failure, thrombocytopenia (abnormally low platelet count) and anemia.

TMA is common among patients with certain ultra-rare, severe complement inhibitor deficiency diseases, including atypical Hemolytic Uremic Syndrome (aHUS), Membranoproliferative Glomerulonephritis (MPGN), Catastrophic Antiphospholipid Syndrome (CAPS) and Paroxysmal Nocturnal Hemoglobinuria (PNH). Research examining the role of Soliris in these disorders was the subject of 10 presentations at the 2nd International Conference on HUS-MPGN-PNH held in Innsbruck, Austria on June 13-15, 2010.

"aHUS, MPGN, CAPS and PNH are diseases characterized by uncontrolled complement activation that share a common pathology of TMA. Research shows that these defects in the body's complement system often result in devastating and life-threatening clinical consequences," said Dr. Lothar Bernd Zimmerhackl, President of the Conference and Professor at the Medical University of Innsbruck. "As we gain more clinical experience and learn more about these diseases, terminal complement inhibition with eculizumab is a promising treatment strategy, since it targets a central mechanism of TMA."

Soliris has been approved by healthcare authorities in the United States, European Union, Japan and other countries as the first treatment for patients with PNH, a rare, debilitating and life-threatening blood disorder defined by hemolysis, or the destruction of red blood cells. Soliris is not approved for the treatment of aHUS, MPGN, CAPS or diarrhea-associated HUS (D+HUS).

"Research presented this week in Innsbruck suggests that Soliris has the potential to benefit patients with a variety of ultra-rare genetic diseases characterized by the presence of TMA," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "Our primary focus is to diligently bring Soliris to patients with PNH in a growing number of countries worldwide. We recognize the often devastating outcomes for patients who have very few and limited therapeutic options, and we are committed to evaluating the safety and efficacy of Soliris in these diseases where we believe complement inhibition could have a dramatic impact on patients' lives."

Early Clinical Experience with Soliris in Atypical HUS
Researchers reported several case studies of patients with atypical Hemolytic Uremic Syndrome (aHUS) treated with Soliris. As previously announced, Alexion has completed enrollment in four prospective, open-label clinical studies investigating Soliris as a potential treatment for patients with aHUS, and preliminary results from these studies are expected later this year. Presentations at the conference included:

  • "Eculizumab in Atypical Hemolytic Uremic Syndrome: Long-Term Clinical Course and Histological Findings," S. Tschumi.
    A nine year-old girl with aHUS requiring plasma exchange was switched to treatment with Soliris (600 mg every two weeks). Nine months after starting Soliris, kidney function remained stable, anti-hypertensive medications were reduced, cardiac thickening was reduced, and quality of life was substantially improved. A renal biopsy performed at two months after starting Soliris showed that there was no evidence of TMA.
  • "Remission of Plasma-Resistant Atypical Hemolytic Uremic Syndrome Relapse on Kidney Graft with Eculizumab," G. Ardissino.
    A six year-old boy with aHUS received a kidney transplant. Two months after the transplant, aHUS exacerbated without any apparent antecedent precipitant resulting in kidney failure requiring dialysis, despite plasma exchange. Soliris treatment was commenced and was associated with improvement in kidney function allowing cessation of dialysis. Investigators noted that Soliris appeared safe in this individual.
  • "Maintenance of Renal Function Under Eculizumab Despite Discontinuation of Plasma Exchange After a Third Transplantation for Atypical Hemolytic Uremic Syndrome Associated with a CFH Mutation," J.C. Davin.
    A 17-year old patient with aHUS and history of multiple severe brain ischemic events underwent a third kidney transplant and was started on plasma exchange therapy. The patient experienced repetitive aHUS exacerbations and also became severely intolerant of plasma with severe allergic reactions. The patient was started on Soliris treatment at the dose of 1200 mg every two weeks and plasma exchange was discontinued. The patient tolerated Soliris well during fifteen months of treatment. During this ongoing treatment her plasma creatinine was stable, and neither aHUS exacerbation nor side-effects have been observed.
  • "Effectiveness of Eculizumab in a Plasma Infusion Dependent Patient with Atypical Hemolytic Uremic Syndrome Associated with Heterozygous Combined De Novo Mutations in Factor H Gene," A.L. Lapeyraque.
    A seven year-old girl with aHUS had been treated prophylactically with plasma infusions and with increased plasma infusion frequency after exacerbations. After plasma infusions were determined to be ineffective, the patient was started on Soliris treatment. The patient experienced immediate and complete inhibition of terminal complement activation. Already during the first week of treatment, her platelet count increased, hemolysis and blood pressure normalized and renal function recovered. The patient is chronically treated with 600 mg of Soliris every two weeks for over six months with no evidence of platelet consumption or hemolysis.
  • "Successful Kidney Transplantation in Four Patients With Factor H Deficiency-HUS," G. Ardissino.
    Four patients with Factor H deficiency HUS (FHD-HUS) had kidney transplants following one plasma exchange before transplant and prophylactic plasma exchanges and plasma infusion after transplant. Two out of the four patients experienced aHUS recurrence despite prophylactic plasma therapy. One patient was managed with Soliris and was reported to have achieved immediate recovery from the recurrence.
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