BioMarin is developing AAV-factor VIII vector, BMN 270, for the treatment of hemophilia A

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BMN 270: AAV-factor VIII vector for Hemophilia A

Current Clinical Trials

BioMarin expects to initiate clinical studies with BMN 270 in early 2015.

What is Hemophilia A?

Hemophilia usually is inherited. “Inherited” means that the disorder is passed from parents to children through genes. People born with hemophilia have little or no clotting factor. Clotting factor is a protein needed for normal blood clotting. There are several types of clotting factors. These proteins work with platelets (PLATE-lets) to help the blood clot.

Platelets are small blood cell fragments that form in the bone marrow—a sponge-like tissue in the bones. Platelets play a major role in blood clotting. When blood vessels are injured, clotting factors help platelets stick together to plug cuts and breaks on the vessels and stop bleeding.

The two main types of hemophilia are A and B. If you have hemophilia A, you’re missing or have low levels of clotting factor VIII (8). About 8 out of 10 people who have hemophilia have type A. If you have hemophilia B, you’re missing or have low levels of clotting factor IX (9).

Source: National Heart, Lung, and Blood Institute

Program Overview

BioMarin is developing AAV-factor VIII vector, BMN 270, for the treatment of hemophilia A. In BioMarin’s hemophiliac factor VIII deficient mouse models, BMN 270 restored factor VIII plasma concentrations to levels projected to be adequate for normal clotting in humans. The standard of care for the 60 percent of hemophilia A patients who are severely affected is a prophylactic regimen of IV infusions three times per week. Even with prophylactic regimens, many patients still experience spontaneous bleeding events that result in progressive and debilitating joint damage due to result of chronically low factor levels.

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New Phase 3 Data Confirm Long-Lasting Characteristics Of ALPROLIX™ and ELOCTATE™ Across Multiple Hemophilia Populations

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Monday, December 9, 2013 11:30 am EST

– Interim Analyses from Phase 3 Pediatric Studies Suggest Prolonged Half-Life of Investigational Long-Lasting Therapies in Children Under Age 12 –

CAMBRIDGE, Mass. & STOCKHOLM–()–Today Biogen Idec (NASDAQ:BIIB) and Swedish Orphan Biovitrum AB (publ) (Sobi) (STO:SOBI) announced new results from Phase 3 studies of their investigational long-lasting recombinant factor IX and VIII Fc fusion protein candidates for hemophilia B and A, ALPROLIXTM and ELOCTATETM, including an interim analysis of pediatric pharmacokinetics (PK) data. These interim data are the first to demonstrate that ALPROLIX and ELOCTATE have consistently prolonged half-lives (a measure of the time therapy circulates in the bloodstream) in children, compared to study participants’ prior therapies. Investigators presented these results, which were consistent with PK results in adults and adolescents, at the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, held on December 7 to 10.

ALPROLIX and ELOCTATE use a technology called Fc fusion and demonstrate prolonged circulation in the body, which has been shown in studies of adults with hemophilia to extend the time between prophylactic infusions.

“As seen in adult studies, interim data demonstrated that in children,  the use of Fc fusion technology prolongs the half-lives of these experimental therapies,” said Guy Young, M.D., director, Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles. “We are investigating whether prophylactic dosing intervals longer than the currently available therapy are possible with these treatments. The frequency of traditional prophylactic regimens is a significant challenge for parents of children with hemophilia, many of whom require infusions multiple times per week.”

Kids B-LONG and Kids A-LONG are ongoing, multi-center Phase 3 studies of ALPROLIX and ELOCTATE for previously treated children under age 12 with hemophilia B and A, respectively. Kids B-LONG and Kids A-LONG are designed to investigate the safety, efficacy and PK of ALPROLIX and ELOCTATE. In Kids B-LONG, the mean half-life of ALPROLIX was more than three times longer than currently available factor IX therapies. The Kids A-LONG interim analysis showed the mean half-life of ELOCTATE was approximately one and a half times that of existing factor VIII therapies. For both ALPROLIX and ELOCTATE, prolonged half-lives were seen in each age group analyzed – under six and six to under 12 years old.

In 43 children treated with ELOCTATE as of February 8, 2013, and 23 children receiving ALPROLIX as of April 23, 2013, no inhibitors (antibodies that may interfere with the activity of the therapy) were detected. Overall, the pattern of treatment-emergent adverse events reported was typical of the populations studied, with no unique safety issues identified.

Final results of the pediatric studies will evaluate the safety and efficacy of ALPROLIX and ELOCTATE, as well as provide further PK information. Investigators plan to report these results at a future medical meeting. The primary endpoint for both studies is the occurrence of inhibitor development over the study period. Secondary outcome measures include the annualized bleeding rate (ABR), or projected number of yearly bleeding episodes, and assessments of response to treatment.

At the meeting, new analyses of data from B-LONG and A-LONG, the Phase 3 studies of ALPROLIX and ELOCTATE in adolescents and adults, were presented. These data provided additional insight into the prophylactic dosing regimens that may be possible with these therapies, if approved. Prophylaxis regimens involve regularly scheduled infusions designed to prevent or reduce bleeding episodes. In these studies, a prolonged half-life helped study participants achieve effective prevention or reduction of bleeding episodes with fewer prophylactic infusions.

“These data underscore our commitment to advancing scientific understanding and innovation in hemophilia, and our goal of introducing the first long-lasting therapies to those with hemophilia,” said Glenn Pierce, M.D., Ph.D., senior vice president of Global Medical Affairs and chief medical officer at Biogen Idec’s hemophilia therapeutic area. “These analyses add to the growing body of data supporting the clinical benefits of ALPROLIX and ELOCTATE in people of different ages with hemophilia B and A, and their potential to reduce bleeding episodes with fewer prophylactic infusions, if approved.”

Less Frequent Prophylactic Dosing Observed with ELOCTATE

A post-hoc analysis of A-LONG participants who were receiving a prophylactic (preventive) regimen with currently available factor VIII therapies prior to the study, evaluated self-reported dose, dose interval and bleeding rates over the preceding 12 months while on currently approved factor VIII therapies. These data points were also collected for on-study ELOCTATE therapy.

The majority of participants reported infusions three times a week with  their previous factor VIII therapy. During the study, 98.8 percent of  participants had ELOCTATE prophylactic dosing regimens with less frequent infusions than they reported using before the study. Their last on-study prophylactic dosing intervals were every three days (36.3 percent), twice weekly (28.8 percent), every four days (5.0 percent) and  every five days (30.0 percent). Overall, these participants reported a median of 6.0 bleeding episodes in the prior year with their existing therapy; in the last three months of on-study ELOCTATE therapy, they had a median annualized bleeding rate of zero. Weekly factor consumption for prophylaxis remained consistent with ELOCTATE and prior therapy for the majority of participants.

“Prophylactic dosing schedules have the potential to be less frequent and reduce bleeding episodes with the emergence of long-lasting therapy,” said Birgitte Volck, M.D., Ph.D., senior vice president development and chief medical officer of Sobi. “These data may help physicians understand how prophylactic dosing schedules could differ between investigational, long-lasting ELOCTATE therapy and currently available factor VIII treatments. The post-hoc analysis showed that ELOCTATE enabled bleeding control for study participants with less frequent prophylactic infusions than their previous therapy.”

Study investigators reported that ELOCTATE was well tolerated, and no inhibitors were detected during the A-LONG study. Safety events were representative of those occurring in the general hemophilia population. Outside of the perioperative (surgical) period, the most common adverse events (incidence of greater than or equal to five percent) included nasopharyngitis (common cold), arthralgia (joint pain), headache and upper respiratory infection.

Hemophilia Quality of Life Measure Validated

This study evaluated the reliability, validity and sensitivity of the Hemophilia-Specific Quality of Life Index (Haem-A-QoL), a 46-item questionnaire used to assess health-related quality of life specifically in people with hemophilia. The analysis used EuroQoL-5 Dimension (EQ-5D) data to validate Haem-A-QoL data collected from participants in the A-LONG and B-LONG studies. EQ-5D is a quality-of-life health assessment tool that is commonly used in late-stage studies for other diseases. These data further validate the usefulness of the Haem-A-QoL measurement in adults with hemophilia.

“Without adequate control over bleeding episodes, hemophilia not only leads to physical complications, but also may impact a person’s ability to attend work or school, enjoy leisure activities or maintain positive mental health,” said Aoife Brennan, M.D., senior medical director, Clinical Development of Biogen Idec’s hemophilia therapeutic area. “To understand these effects, we are committed to examining the impact of our investigational therapies ALPROLIX and ELOCTATE on a broad range of measurements, including quality-of-life measurement tools. A preliminary analysis of Haem-A-QoL scores in A-LONG and B-LONG showed numerical improvements in total scores from baseline, and we are conducting further analyses to understand the potential clinical implications of these results.”


ALPROLIX and ELOCTATE are investigational fully recombinant, long-lasting clotting factor therapies being developed for hemophilia B and A, respectively. They use Fc fusion technology, which takes advantage of a naturally occurring pathway that delays the breakdown of Immunoglobulin G Subclass 1, or IgG1 (protein commonly found in the body), and cycles it back into the bloodstream. The Fc portion of IgG1 is fused to factors IX and VIII in ALPROLIX and ELOCTATE, respectively.  This technology is thought to be responsible for the prolonged time ALPROLIX and ELOCTATE circulate in the body. While Fc fusion is an established technology that has been used for more than 15 years, Biogen Idec is the only company to apply it in hemophilia.

Based on Phase 3 study results, prophylactic therapy with ALPROLIX and ELOCTATE may help prevent or reduce bleeding episodes in people with severe hemophilia B and A, respectively. Regulatory applications for both therapies are currently under review in several countries including the United States, Canada and Australia.

About the Biogen Idec and Sobi Collaboration

Biogen Idec and Swedish Orphan Biovitrum (Sobi) are partners in the development and commercialization of ALPROLIX for hemophilia B and ELOCTATE for hemophilia A. Biogen Idec leads development, has manufacturing rights, and has commercialization rights in North America and all other regions excluding the Sobi territory. Sobi has the right to opt in to assume final development and commercialization in Europe (including Russia), the Middle East and Northern Africa.

About Biogen Idec

Through cutting-edge science and medicine, Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hemophilia and autoimmune disorders. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $5 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit

About Sobi

Sobi is an international specialty healthcare company dedicated to rare diseases. Our mission is to develop and deliver innovative therapies and services to improve the lives of patients. The product portfolio is primarily focused on inflammation and genetic diseases, with three late stage biological development projects within hemophilia and neonatology. We also market a portfolio of specialty and rare disease products for partner companies. Sobi is a pioneer in biotechnology with world-class capabilities in protein biochemistry and biologics manufacturing. In 2012, Sobi had total revenues of SEK 1.9 billion (€ 215 M) and about 500 employees. The share (STO: SOBI) is listed on NASDAQ OMX Stockholm. More information is available at

Biogen Idec Safe Harbor

This press release contains forward-looking statements, including statements about the potential impact and therapeutic effect of ALPROLIX and ELOCTATE, our investigational long-lasting recombinant factor product candidates. These statements may be identified by words such as “believe,” “expect,” “may,” “plan,” “potential,” “will” and similar expressions, and are based on our current beliefs and expectations. Drug development and commercialization involve a high degree of risk. Factors which could cause actual results to differ materially from our current expectations include the risk that unexpected concerns may arise from additional data or analysis, regulatory authorities may require additional data or information or further studies, or may fail to approve or may delay approval of our drug candidates, or we may encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with our drug development and commercialization activities, please review the Risk Factors section of our most recent annual or quarterly report filed with the Securities and Exchange Commission. Any forward-looking statements speak only as of the date of this press release and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

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Media Contact: Todd Cooper,
+1 781  464 3260
Investor Relations Contact: Ben Strain,
+1 781 464 2442
Media Contact: Charlotte af Klercker,
+46 70 729 7327
Analyst/Investor Contact: Jörgen Winroth,
+46 8 697 2135

For Entire Press release, Click HERE.

Hybrid Clotting Factor Means Fewer Injections, Better Disease Control for Hemophilia Patients

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Sacramento, Calif. (PRWEB) December 12, 2013

A Phase III clinical trial led by UC Davis researchers has confirmed that a new coagulation factor (rFIXFc) dramatically reduces the number of injections needed to maintain effective clotting for hemophilia B patients.

The recombinant protein fuses clotting factor IX with an immunoglobulin (antibody) molecule, which prevents the body from rapidly metabolizing the hybrid protein. As a result, rFIXFc can be administered once a week, or even every two weeks, rather than every other (or every third) day. This extended half-life could have an enormous impact on hemophilia treatment. The findings appeared in today’s New England Journal of Medicine.

“The major challenge is spontaneous bleeding, either in weight-bearing joints or internally,” said lead investigator Jerry Powell, who directs the UC Davis Hemophilia and Thrombosis Center. “These events can be painful, life-threatening or both. To compound matters, teenage boys often drop off infusing, increasing their risk. Fewer injections should improve compliance.”

Hemophilia B is a congenital disorder caused by reduced levels of clotting factor IX, a protein that helps blood coagulate. By contrast, hemophilia A, the most common form of the disease, is caused by a loss of factor VIII. These conditions almost always affect men.

The trial enrolled 123 patients, 12 or older, who had been treated previously for hemophilia B and was divided into four groups: the first received weekly injections; the second received higher doses every 10 days; the third was only treated for specific bleeding episodes; and the fourth focused on how patients fared while undergoing surgery. An additional subgroup compared rFIXFc’s half-life in the body to that of recombinant factor IX.

The median treatment time was 51.6 weeks, during which compliance was excellent: 95.1 percent in group 1 and 100 percent in group 2. But most importantly, the annualized bleeding rate was reduced by 83 percent in group 1 and 87 percent in group 2, compared to patients receiving episodic treatment in group 3.

In addition, 23 percent of patients in group 1 and 42.3 percent in group 2 experienced no bleeding at all. In group 4, there were 14 surgeries, during which bleeding was well-controlled.

Before the study, more than 80 percent of participants in the first two groups injected at least twice a week. However, with rFIXFc, they only needed to infuse once a week, or every two weeks, to effectively control their bleeding.

While recombinant clotting factors have dramatically extended lifespans for hemophiliacs, the proteins’ short half-lives have been a limiting factor. The problem stemmed from lysosomes, cellular “chop shops” that break down proteins and other molecules. However, fusing an immunoglobulin molecule to factor IX allows the hybrid protein to temporarily escape the lysosomes, providing coagulation protection for a much longer period.

“This is a major innovation,” said Powell. “The body handles rFIXFc like an immunoglobulin molecule, but the factor retains its ability to stop bleeding.”

Some issues still need to be resolved. For example, as many as 3 percent of patients have an immune reaction to factor IX. Because the study was narrowly focused on whether the combined factor would effectively control bleeding, and all participants had successfully used factor IX, researchers did not address whether previously untreated hemophiliacs would develop an immune response to rFIXFc. This question will be addressed in future research. However, none of the study participants had an immune reaction to rFIXFc.

In addition, although the new factor is designed to treat only hemophilia B, the trial’s success outlines an effective strategy to develop long-lasting factors for other forms of the disease.

“This is the first modification to coagulation factors to increase the half-life,” Powell said. “My hope is that other pharmaceutical companies will focus on developing additional long-lasting factors to treat other types of hemophilia.”

The recombinant protein rFIXFc was created by Biogen-Idec. The company paid for extra staff to coordinate the study and lab tests and provided rFIXFc for the trial. In addition, some patients were reimbursed for travel expenses. Powell did not receive any compensation from Biogen-Idec to conduct the research.

For original Article, click here.

Baxter Receives FDA Approval of FEIBA [Anti-Inhibitor Coagulant Complex] for Prophylactic Treatment of Hemophilia A&B Patients with Inhibitors

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Pivotal Phase III data showed 72% reduction in median annual bleed rate with FEIBA prophylactic treatment compared to an on-demand regimen

For Original Press release, click here.

DEERFIELD, Ill., December 19, 2013 – Baxter International Inc. (NYSE:BAX) today announced that the United States Food and Drug Administration (FDA) granted approval of Baxter’s FEIBA [Anti-Inhibitor Coagulant Complex], the first and only FDA-approved treatment for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors.

Inhibitor development is considered one of the most serious complications associated with hemophilia treatment today. As many as one-third of previously untreated patients with severe or moderately severe hemophilia A are at risk for developing inhibitors, which are antibodies produced by the body’s immune system in response to factor replacement treatment. The presence of an inhibitor makes response to treatment more challenging, and patients with inhibitors have an increased risk of developing complications.

The approval is based on data from a pivotal Phase III study, known as FEIBA PROOF, in which treatment with a FEIBA prophylactic regimen showed a 72 percent reduction in median annual bleed rate (ABR) compared to treatment with an on-demand regimen. In the intent-to-treat (ITT) analysis, three of the 17 (18%) adult patients in the prophylactic arm reported no bleeding episodes. The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting. The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

“The PROOF study demonstrated that a prophylactic regimen with FEIBA can significantly reduce the rate of bleeding episodes, as compared to an on-demand regimen, in hemophilia patients with inhibitors. This is important among these patients who often have difficult-to-treat bleeds and are at risk of additional complications,” said Steven Pipe, M.D., Director, Division of Pediatric Hematology and Oncology, at the C.S. Mott Children’s Hospital at the University of Michigan. “This FDA approval of a prophylactic regimen should change the way physicians think about managing hemophilia with inhibitors, validating FEIBA prophylaxis as an effective new option to treat their patients.”

Pro-FEIBA, a prospective investigator-initiated, randomized, crossover study published in the New England Journal of Medicine in 2011 showed a 62 percent reduction in all bleeding episodes with FEIBA prophylaxis compared to an on-demand regimen. Together with the data from the FEIBA PROOF study, the results provide valuable evidence that prophylaxis with FEIBA can significantly reduce bleeding rates when compared to on-demand treatment.

“FEIBA has been an effective treatment for hemophilia patients with inhibitors for more than 35 years as an on-demand treatment. FEIBA was first licensed in the US as FEIBA VH and then as FEIBA NF. This additional indication for prophylactic treatment is aimed at reducing the number of bleeds among this patient population,” said Ludwig Hantson, Ph.D., president of Baxter’s BioScience business. “This latest approval reflects our legacy of offering new approaches to help reduce the disease burden of hemophilia, and supports Baxter’s ongoing commitment to pursuing a bleed-free world.”

FEIBA is approved in more than 60 countries worldwide and is indicated for prophylaxis in more than 40 countries.

FEIBA PROOF Study Details The prospective, open label, randomized, multi-center, two-arm parallel study investigated the efficacy and safety of FEIBA prophylactic treatment compared to on-demand treatment in 36 patients with hemophilia A or B with inhibitors over a 12-month period. The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting. The occurrence of hepatitis B surface antibodies has been seen in other plasma-derived products and could be due to the passive transfer of antibodies following FEIBA treatment. None of the subjects showed any signs of active hepatitis B infection.

Indications and Detailed Important Risk Information for FEIBA [Anti-Inhibitor Coagulant Complex] FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:

  • Control and prevention of bleeding episodes
  • Perioperative management
  • Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation Factor VIII or coagulation Factor IX.

Detailed Important Risk Information


  • Thromboembolic events have been reported during post-marketing surveillance, particularly following the administration of high doses and/or in patients with thrombotic risk factors.
  • Monitor patients receiving FEIBA for signs and symptoms of thromboembolic events.

The use of FEIBA is contraindicated in patients with:

  • Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system
  • Disseminated intravascular coagulation (DIC)
  • Acute thrombosis or embolism (including myocardial infarction)

Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur with FEIBA, particularly following the administration of high doses (above 200 units per kg per day) and/or in patients with thrombotic risk factors.

Infusion of FEIBA should not exceed a dose of 100 units per kg body weight every 6 hours and daily doses of 200 units per kg body weight. Monitor patients receiving more than 100 units per kg of body weight of FEIBA for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue the infusion and initiate appropriate diagnostic and therapeutic measures.

Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur following the infusion of FEIBA. The symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. These reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of FEIBA and provide appropriate supportive care.

Because FEIBA is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting.

The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended.

Please see the FEIBA full Prescribing Information at: products/feiba_us_pi.pdf.

About Hemophilia Hemophilia is a rare genetic blood clotting disorder that primarily affects males.1  People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood.1  Two of the most common forms of hemophilia are A and B.2  In people with hemophilia A, clotting factor VIII (FVIII) is not present in sufficient amounts or is absent.2  Without enough FVIII, people with hemophilia can experience spontaneous, uncontrolled internal bleeding that is painful, debilitating, damaging to joints and potentially fatal.2  People with hemophilia B (also called Christmas disease) do not have sufficient amounts of clotting factor IX.2  In about 30% of cases, there is no family history of hemophilia and the condition is the result of a spontaneous gene mutation.3  According to the World Federation of Hemophilia, it is estimated that more than 400,000 people in the world have hemophilia.2 All races and economic groups are affected equally. It is estimated that approximately 17,000 people in the U.S. have been diagnosed with hemophilia A or B.4

About Inhibitors As many as one-third of previously untreated patients with severe or moderately severe hemophilia A are at risk for developing inhibitors,5,6,7 which are antibodies produced by the body’s immune system in response to factor replacement treatment.8,9  The presence of an inhibitor makes response to treatment more challenging, and patients with inhibitors have an increased risk of developing complications such as joint damage.10  Inhibitors cause the body to work against the factor replacement treatment, neutralizing its effect and preventing an individual’s blood from clotting.10,11  Individuals who have inhibitors have a form of hemophilia that is more difficult to control, with an increased risk of uncontrolled bleeding, compared to patients without inhibitors.  Inhibitor development is considered one of the most serious complications associated with hemophilia treatment, and may include other associated complications such as impaired movement, increased need for surgery and greater complexity or risk associated with surgery.12,13

About Baxter International Inc. Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

1About Bleeding Disorders: Treatment. World Federation of Hemophilia. Accessed on: October 9, 2013. Available at:
2Frequently Asked Questions about Hemophilia. World Federation of Hemophilia. Accessed on: October 9, 2013. Available at: 
3Hemophilia A. National Hemophilia Foundation. Accessed on: October 9, 2013. Available at: .
4World Federation of Hemophilia Report on the Annual Global Survey 2011. World Federation of Hemophilia. Accessed on October 9, 2013. Available at:
5Ehrlich HJ, Bray GL, Gomperts ED.: Comparison of high responder inhibitor frequency in recent studies of previously untreated patients with hemophilia A. Thromb.Haemost. 1998;79: 242-243.
6Kreuz W, Escuriola-Ettingshausen C, Zyschka A eta!.: Inhibitor development in previously untreated patients with hemophilia A: a prospective long-term follow-up comparing plasma-derived and recombinant products. Semin.Thromb.Hemost.2002;28: 285-290.
7Hay CR: Factor VIII inhibitors in mild and moderate-severity haemophilia A. Haemophilia. 1998;4: 558-563.
8Santagostino E, Mancuso ME, Rocino A, et al. Environmental risk factors for inhibitor development in children with haemophilia A: a case-control study. Br J Haematol. 2005;130:422-427.
9Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia. 2006;12(Suppl. 6):15-22.
10Perry D, Berntorp E, Tait C, et al. FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations. Haemophilia. 2010;16:80-89.
11About Bleeding Disorders. What are Inhibitors?. World Federation of Hemophilia. Accessed on October 9, 2013. Available at: .
12Leissinger, Cindy A. Prevention of Bleeds in Hemophilia Patients with Inhibitors: Emerging Data and Clinical Direction. American Journal of Hematology. 2004; 77:187-193.
13Kulkarni R. Comprehensive care for the patient with haemophilia and inhibitors undergoing surgery: practical aspects. Haemophilia. 2013;19:2-10.

Spark Therapeutics Launched with $50 Million in Financing to Advance Late- and Mid-Stage Gene Therapy Programs with Clinical Proof of Concept

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Fully Integrated Gene Therapy Company with Deep Clinical Pipeline Spun out of The Children’s Hospital of Philidelphia


PHILADELPHIA, Oct. 22, 2013 — Spark Therapeutics, a new, fully integrated company developing gene-based medicines for a wide range of debilitating diseases, announced today it has launched with a $50 million capital commitment from The Children’s Hospital of Philadelphia (CHOP) to advance and commercialize multiple ongoing programs with clinical proof of concept.

Spark will assume control over two gene therapy clinical trials: a Phase 3 study for inherited blindness caused by mutations of the RPE65 gene and a Phase 1/2 study for hemophilia B. The company is also advancing toward the clinic with gene therapy programs to address neurodegenerative diseases and additional hematologic disorders and other forms of inherited blindness.

“The creation of Spark is the culmination of a decade-long commitment by CHOP and our founding team to drive the field of gene therapy forward during a time when many in the industry had moved away,” said Jeffrey D. Marrazzo, co-founder, president and chief executive officer of Spark Therapeutics. “Their vision and long-term dedication have enabled us to effectively address many of the key challenges facing the field and to emerge with one of the industry’s most robust clinical-stage gene therapy pipelines; as well as exclusive rights to commercialize a proprietary manufacturing platform, supply from a world-class manufacturing facility and a founding team with a proven track record of executing safe and effective gene therapy trials for nearly two decades. We are working with great urgency and care to deliver gene therapy products with the potential to transform the lives of those affected by severe genetic diseases.”

Spark builds on the work of CHOP’s Center for Cellular and Molecular Therapeutics (CCMT), established in 2004 as a world-class center for gene therapy translational research and manufacturing. Many of the CCMT’s leaders will assume management roles within Spark or engage with the company as scientific advisors, including Katherine A. High, M.D, a gene therapy pioneer who has served as the director of the CCMT since its inception.

“Gene-based medicines are among the most complex therapeutics ever developed,” said Dr. High. “We at CCMT have persevered through more than a decade of scientific and clinical development and are now closer than ever to realizing the ambitious vision of one-time, potentially curative therapies to address serious genetic conditions. The team at Spark has incredible goals for the treatment of diseases including hemophilia B and inherited blindness, and we look forward to working with them to deliver groundbreaking new treatments to patients in need.”

Spark has entered into agreements with multiple academic institutions to assemble the technology, programs and capabilities needed to deliver its pioneering gene therapy products. Notably, Spark has exclusive rights to commercialize CHOP’s proprietary manufacturing technology and will use clinical-grade gene therapy vectors produced by the CCMT’s state of the art good manufacturing practices (cGMP) clinical facility.

Pioneers in AAV delivery    Over the past two decades, the Spark leadership team has developed unrivaled expertise in the design, manufacturing and delivery of gene therapies using adeno-associated virus (AAV) vectors. AAV has been demonstrated in clinical studies to be a safe and effective vehicle for the delivery of genetic material into targeted cells and provides unique advantages over alternative delivery approaches. The Spark team was among the first to demonstrate human clinical proof of concept in two distinct organ systems—the eye and the liver—establishing a strong foundation for the company’s current programs, and has clinical experience in 15 studies across diverse genetic and non-genetic diseases and five distinct routes of administration.

Spark’s most advanced clinical program is a Phase 3 study to address blindness caused by mutations in the RPE65 gene. There is currently no pharmacologic treatment for this form of inherited retinal degeneration, which ultimately causes irreversible blindness.

The open-label, randomized, controlled study builds on an earlier clinical study in which 12 patients with RPE65-related blindness demonstrated notable improvement in visual function, moving in some cases from being profoundly blind to being able to recognize faces and ambulate independently. All school-age patients enrolled in the trial were able to transfer from Braille classrooms to sighted classrooms.

In hemophilia B, the company’s Phase 1/2 study is enrolling up to 15 subjects who will receive a one-time dose through an intravenous infusion of the gene responsible for expressing factor IX. The open-label, dose escalation study is designed to assess safety and effectiveness of gene therapy in inducing the body to create native factor IX, as measured in their blood. If successful, gene therapy in hemophilia B would eliminate or reduce the need for regular infusions of clotting factor, enabling physicians to provide comprehensive, accessible treatment to all hemophilia B patients, potentially including those with inhibiting antibodies.

This study builds on the Spark team’s previous groundbreaking work in advancing the first two gene therapy clinical studies in hemophilia B, the second of which achieved the highest levels of factor IX expression of any gene therapy trial to date.

Leading expertise   Spark’s founding team includes gene therapy scientists and experts in clinical development and manufacturing who have been at the forefront of the effort to advance gene therapy as a viable treatment paradigm for debilitating, incurable diseases. Spark’s team has more than 120 years of combined experience addressing the clinical, regulatory and manufacturing issues related to gene-based medicines.

  • Jean Bennett, M.D., Ph.D., scientific co-founder and advisor, has more than 20 years’ experience researching inherited retinal conditions and led the first team to demonstrate preclinical proof of principle in ocular gene therapy.
  • Beverly Davidson, Ph.D., scientific co-founder and advisor, has worked for nearly 20 years in developing gene therapies to address genetic diseases that cause central nervous system dysfunction.
  • Bernd Hauck, Ph.D., an advisor on clinical vector operations, has served as the assistant director of production at the CCMT vector manufacturing facility, establishing standard operating procedures for the AAV vector manufacturing process.
  • Katherine A. High, M.D., scientific co-founder and advisor, is a Howard Hughes Medical Institute investigator, director of the CCMT, was elected a fellow of the American Association for the Advancement of Science based on “distinguished contributions in the field of human gene therapy,” and is a former president of the American Society of Gene & Cell Therapy (ASGCT).
  • Jeffrey D. Marrazzo, M.B.A., M.P.A., co-founder, president and CEO, is an experienced entrepreneur dedicated to curing disease through genomic medicine and has held leadership roles at several successful molecular and cellular medicine companies including Generation Health, MolecularHealth, Inc., and Tengion.
  • Guang Qu, Ph.D., M.S., vice president of process development, has over 15 years’ working experience in the gene therapy field, including six years in the biotechnology industry directing process development at Avigen, Inc.
  • Junwei Sun, M.S., an advisor on R&D operations, has served as the administrative director for the CCMT since its inception.
  • Jennifer Wellman, vice president of regulatory affairs, has 13 years of R&D and regulatory experience specifically related to AAV-mediated gene therapy and has spent the past eight years at the CCMT where she directed regulatory interactions for the Center’s gene therapy studies. She previously worked at Avigen, Inc.
  • J. Fraser Wright, Ph.D., scientific co-founder and chief technology advisor, is a leading expert in clinical vector production and characterization and has directed the CCMT’s vector manufacturing since its establishment. He has overseen investigational product chemistry, manufacturing and controls for gene therapy vectors administered to more than 100 human subjects in 12 clinical studies.

About Spark Therapeutics      Spark Therapeutics is developing potentially curative, one-time gene therapy products to transform the lives of patients and re-imagine the treatment of debilitating diseases. The founding team includes scientists who led the movement to develop gene therapy as a new treatment paradigm, establishing clinical proof of concept in the eye and liver and contributing key insights to the field that have resulted in a resurgence of industry interest in gene-based medicines. Our robust pipeline includes a Phase 3 program in blindness due to mutations in the RPE65 gene and a Phase 1/2 program in hemophilia B, as well as preclinical programs to address neurodegenerative diseases and other retinal degenerative diseases and hematologic disorders. Spark has rights to a proprietary manufacturing platform that has an unparalleled track record of success in supporting clinical studies across diverse therapeutic areas and routes of administration. The company’s expertise across research, clinical, regulatory and manufacturing builds on a legacy of innovation and excellence in gene therapy established by Spark’s team while at The Children’s Hospital of Philadelphia Center for Cellular and Molecular Therapeutics. To learn more visit

Media Inquiries:
Jessica Rowlands

Free Genetic Testing Initiative to be Available Nationally at Hemophilia Treatment Centers

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Free Genetic Testing Initiative to be Available Nationally at Hemophilia Treatment Centers

- My Life, Our Future pilot phase successfully completed -
- Initiative aims to offer genotyping to all people affected by the disorder in the United States -
-May help improve treatment and care today, and advance future hemophilia research -

ANAHEIM, CA. - October 2, 2013 – Today, a coalition of leaders in hemophilia advocacy and treatment announced the national rollout of My Life, Our Future: Genotyping for Progress in Hemophilia, which offers genetic testing, or genotyping, to people with hemophilia, a rare genetic disorder that impairs the ability of the blood to clot properly. Following the successful completion of an eleven site pilot program, hemophilia treatment centers (HTCs) across the U.S., where the majority of people with hemophilia receive care, can now participate in the program and offer genotyping to the patients they serve.

My Life, Our Future is a partnership of the National Hemophilia Foundation (NHF), the American Thrombosis and Hemostasis Network (ATHN), Puget Sound Blood Center (PSBC), and Biogen Idec (NASDAQ: BIIB). Through genotyping, it is possible to identify the specific DNA mutation(s), or change(s), responsible for a person’s hemophilia and provide potentially useful information about his/her bleeding severity or risk for inhibitors, a major complication of hemophilia that involves an immune response to treatment. Through My Life, Our Future, participants can also contribute their data and samples to a secure central research repository, which can serve as a roadmap to greater scientific understanding of the disorder.

My Life, Our Future is a potential opportunity to shape the future of hemophilia treatment and care,” said Val Bias, chief executive officer, NHF. “I urge all people with hemophilia to participate; by enrolling at a participating HTC, they have a chance to learn more about their disorder today while furthering scientific advances tomorrow.”

Barbara Konkle, M.D., director of clinical and translational research, PSBC, emphasized the value of genotyping the entire hemophilia community and creating a robust data repository for future research. “By examining a large amount of genetic material rather than individual samples, we may be able to answer important questions such as why some patients bleed more than others or experience greater joint damage. Armed with this information, physicians may be able to better care for their patients and scientists may be able to develop more targeted treatments.”

My Life, Our Future was initially rolled out to eleven HTCs as part of a pilot program. Since the initiation of that pilot, 275 people with hemophilia enrolled in My Life, Our Future, with the majority opting to contribute to the research repository. Diane Aschman, MS, president and chief executive officer of ATHN, is hopeful that HTCs across the country will participate and provide this valuable service to patients who would not otherwise have access to genotyping.

My Life, Our Future is the first program to make a free genotyping test widely available to people in the U.S. with hemophilia A and B. In contrast to many developed countries where genotyping is considered standard of care, only about 20 percent of people with hemophilia in the U.S. have been genotyped, largely due to cost and insurance coverage barriers.

My Life, Our Future enables us to offer something valuable to our patients,” said Lisa Baker, hemophilia nurse, Hemophilia Treatment Center of Central Pennsylvania at Penn State Milton S. Hershey Medical Center, a HTC participating in the program. “We have long known the benefits of genotyping but many of our patients couldn’t participate due to cost or insurance restrictions.”

“As part of Biogen Idec’s enduring commitment to help address unmet needs in the hemophilia community, we are honored to be a founding partner of this long-sought and important initiative,” said Glenn Pierce, M.D., Ph.D., senior vice president of Global Medical Affairs and chief medical officer of Biogen Idec’s hemophilia therapeutic area, which is providing scientific collaboration and financial support for the program. The company will not have special access to the data or samples generated by the initiative.

About My Life, Our Future: Genotyping for Progress in Hemophilia My Life, Our Future is a partnership of the National Hemophilia Foundation (NHF), the American Thrombosis and Hemostasis Network (ATHN), Puget Sound Blood Center (PSBC), and Biogen Idec Hemophilia. The program offers a free genotyping test to people in the U.S. with hemophilia A and B. Over time, the program will be expanded to include potential carriers in their families. For more information and a list of participating hemophilia treatment centers as they become available, visit

About The National Hemophilia Foundation (NHF)

The National Hemophilia Foundation (NHF) is dedicated to finding better treatments and cures for inheritable bleeding disorders and to preventing the complications of these disorders through education, advocacy and research. Established in 1948, NHF is based in New York City with 51 chapters throughout the United States. NHF’s programs, initiatives and events are made possible through the generosity of individuals, corporations and foundations as well as through a cooperative agreement with the Centers for Disease Control and Prevention (CDC). For more information, visit NHF online at

About The American Thrombosis and Hemostasis Network (ATHN)

The American Thrombosis and Hemostasis Network (ATHN) is a non-profit organization committed to advancing and improving care for individuals affected by bleeding and thrombotic disorders. ATHN’s mission is to provide stewardship of a secure national database, adherent to all privacy guidelines, which will be used to support clinical outcomes analysis, research, advocacy and public health reporting in the hemostasis and thrombosis community. ATHN represents over 130 Hemophilia Treatment Centers. More information is available at

About The Puget Sound Blood Center (PSBC)

Puget Sound Blood Center is an independent, community-based nonprofit organization with a tradition blending volunteerism, medical science and research to advance transfusion medicine and improve patient care. A recognized leader in transfusion medicine, the Blood Center serves patients in more than 70 hospitals and clinics in 14 Western Washington counties. Patients with leukemia, cancer, hemophilia, thrombosis, sickle cell disease and traumatic injuries depend on Blood Center research. PSBC has a state-of-the art laboratory with world-class expertise in hemophilia mutation analysis. More information is available at

About Biogen Idec

Through cutting-edge science and medicine, Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, Hemophilia and autoimmune disorders. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company, and patients worldwide benefit from its leading multiple sclerosis therapies. For more information, please visit

Media Contacts

Kathleen Van Gorden
(401) 480-1840
Keith Hudson

(917) 992-4403

Karen Kirby
(206) 292-4670
              Biogen Idec
Andrew Law
(781) 464-2139

Certain F8 mutations increased inhibitor formation in hemophilia A

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Eckhardt CL. Blood. 2013:10.1182/blood-2013-02-483263.

October 2, 2013

Nineteen specific mutations in the Factor VIII gene were associated with inhibitor development in patients with nonsevere hemophilia A, according to the results of a retrospective cohort study.

The results demonstrate the value of Factor VIII genotyping in this patient population, researchers wrote.

“The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients,” Corien de Groot-Eckhardt, MD, a pediatric resident and PhD student in the department of pediatric hematology and department of vascular medicine at Emma Children’s Hospital in Amsterdam, told HemOnc Today. “These findings are highly relevant for clinical practice as they facilitate identification of high-risk patients based on their F8 genotype.”

De Groot-Eckhardt — along with Karin Fijn van Draat, MD, PhD, of the department of pediatric hematology at Emma Children’s Hospital in Amsterdam, and colleagues — conducted the multicenter INSIGHT study to analyze risk for inhibitor development after treatment with Factor VIII concentrates in 1,112 patients with nonsevere hemophilia A. Researchers identified the F8 genotype in 895 (81%) patients.

Prior studies have demonstrated that the risk for inhibitor development in patients with severe hemophilia A is less than 1% after 50 days of exposure to Factor VIII concentrates. However, most adults with nonsevere hemophilia A haven’t been exposed for this length of time, and thus are still at risk for inhibitor development and resulting complications, researchers wrote.

Nonsevere hemophilia was defined as baseline Factor VIII activity of 2 IU/dL to 40 IU/dL . Eligible patients had Factor VIII concentrate treatment between 1980 and 2011.

The observation period encompassed 25,700 patient-years 44,800 exposure days.

Each patient was exposed for a median of 24 days (interquartile range [IQR], 7-90). At follow-up, exposure did not exceed 50 days in 755 (68%) patients, with 517 of those having less than 20 days of exposure.

Researchers used two positive Bethesda Inhibitor Assay titers of ≥1.0 BU/mL to define inhibitor development. If the inhibitor titers were between 0.6 BU/ml and 1.0 BU/mL, patients also had to have at least a 50% decrease in Factor VIII plasma from baseline or a reduction in half-life after less than 6 hours of treatment for classification of new inhibitors.

Fifty-nine patients (median age, 46 years; median exposure days, 28) developed inhibitors, equating to a cumulative incidence of 5.3% (95% CI, 4.0-6.6; median peak titer, 9 BU/mL). The researchers found no association between inhibitor development and ethnicity or disease severity.

The majority of inhibitors developed between 2000 and 2010 (n=37; 64%), with a median of 32 days of exposure (IQR, 21-75). Seventeen inhibitors (29%) developed between 1990 and 1999, with a median of 12 days of exposure (IQR, 8-41), and four inhibitors (7%) developed between 1980 and 1989, with a median 11 days of exposure (IQR, 6-75).

Researchers calculated the inhibitor risk at 50 exposure days as 6.7% (95% CI, 4.5-8.9), and the risk at 100 exposure days was 13.3% (95% CI, 9.6-17).

“Importantly, the risk of inhibitor development in patients with nonsevere hemophilia approaches the risk of severe hemophilia patients when inhibitor development is evaluated as a function of exposure to Factor VIII concentrates,” the researchers wrote. “This highlights the substantial risk of inhibitor development in nonsevere hemophilia A patients that has been previously underestimated.”

Of the 59 patients who developed inhibitors, researchers reported increased bleeding tendency at detection in 30 (51%) of them, and 47 (80%) needed treatment for bleeding.

After a median of 45 weeks (IQR, 13-108), inhibitors could no longer be detected in 42 (71%) of patients, 12 of whom had undergone inhibitor eradication therapy. Fourteen patients still had inhibitors at the end of follow-up.

Fifty-one (86%) of patients who developed inhibitors had the F8 genotype. At 50 exposure days, the risk for inhibitor development with specific F8 mutations varied from 0% to 42%.

The researchers found that 19 out of 214 F8 mutations, each located in the A2 domain of the heavy chain and the A3, C1 and C2 domains of the light chain, were associated with inhibitor development. Two of those mutations, Phe1775Val and Stop2333Cys, had not previously been reported in the HaMSTERS or CHAMP database, according to researchers. Five of the mutations — Leu412Phe, Arg1781Gly, Phe2101Cys, Arg2159Cys and His2309Asp — had not been previously reported as related to inhibitor development.

“Our study highlights the potential of F8 genotyping to estimate individualized risks of inhibitor formation for those mutations with sufficient data,” the researchers wrote. “It can inform the patient–doctor consultation, contributing to the decision whether to proceed with an elective intervention and how to manage it, and may therefore be of immediate clinical relevance.”

Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.

Corien de Groot-Eckhardt, MD, can be reached at Department of Pediatric Hematology, Emma Children’s Hospital, Academic Medical Center, Meibergdreef 9, Room F4-146, 1105AZ Amsterdam, The Netherlands.


Click here for the review and Perspectives of this study.

Alnylam Receives Orphan Drug Designation from U.S. Food & Drug Administration

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Alnylam Receives Orphan Drug Designation from U.S. Food & Drug Administration for ALN-AT3, an RNAi Therapeutic for the Treatment of Hemophilia

Press Release: Alnylam Pharmaceuticals, Inc. – Wed, Aug 14, 2013 8:00 AM EDT


Alnylam  Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics  company, announced today that the U.S. Food & Drug Administration (FDA)  has granted an Orphan Drug Designation to ALN-AT3 as a therapeutic for  the treatment of hemophilia B. Alnylam is developing ALN-AT3, a  subcutaneously administered RNAi therapeutic targeting antithrombin  (AT), for the treatment of hemophilia – including hemophilia A,  hemophilia B, and hemophilia A or B with “inhibitors” – and other Rare  Bleeding Disorders (RBD).

“We are very pleased to have received Orphan Drug Designation from the  FDA for ALN-AT3, a key program in our ‘Alnylam 5×15’ product development  and commercialization strategy. We believe that our subcutaneously  delivered RNAi therapeutic represents an innovative approach for the  management of hemophilia and has great potential to make a meaningful  impact in the treatment of this often debilitating bleeding disorder,”   said Saraswathy (Sara) Nochur, Ph.D., Senior Vice President, Regulatory  Affairs and Quality Assurance at Alnylam. “We look forward to advancing  this important program towards the clinic in the months to come.”

At the recent Congress of the International Society on Thrombosis and  Haemostasis, Alnylam presented pre-clinical  data demonstrating that ALN-AT3 can normalize thrombin generation  and improve hemostasis in hemophilia mice and can fully correct thrombin  generation in a non-human primate (NHP) hemophilia “inhibitor” model.  ALN-AT3 utilizes the company’s proprietary GalNAc conjugate delivery  platform, enabling subcutaneous dose administration. Alnylam plans to  file an investigational new drug (IND) application for ALN-AT3 in the  fourth quarter of 2013 and initiate a Phase I clinical trial in early  2014.

The FDA Office of Orphan Products Development (OOPD) mission is to  advance the evaluation and development of products that demonstrate  promise for the diagnosis and/or treatment of rare diseases or  conditions. OOPD provides incentives for sponsors to develop products  for rare diseases. The Orphan Drug Designation program provides orphan  status to drugs and biologics which are defined as those intended for  the safe and effective treatment, diagnosis or prevention of rare  diseases/disorders that affect fewer than 200,000 people in the U.S.

About Hemophilia and Rare Bleeding Disorders (RBD)

Hemophilias are hereditary disorders caused by genetic deficiencies of  various blood clotting factors, resulting in recurrent bleeds into  joints, muscles, and other major internal organs. Hemophilia A is  defined by loss-of-function mutations in factor VIII, and there are  greater than 40,000 people in the U.S. and E.U. Hemophilia B, defined by  loss-of-function mutations in factor IX, affects greater than 9,500  people in the U.S. and E.U. Other Rare Bleeding Disorders (RBD) are  defined by congenital deficiencies of other blood coagulation factors,  including Factors II, V, VII, X, and XI, and there are about 1,000  people worldwide with a severe bleeding phenotype. Standard treatment  for people with hemophilia involves replacement of the missing clotting  factor either as prophylaxis or on-demand therapy. However, as many as  one third of people with hemophilia A will develop an antibody to their  replacement factor – a very serious complication; these ‘inhibitor’  subjects become refractory to standard replacement therapy. There exists  a small subset of people with hemophilia who have co-inherited a  prothrombotic mutation, such as factor V Leiden, antithrombin  deficiency, protein C deficiency, and prothrombin G20210A. People with  hemophilia that have co-inherited these prothrombotic mutations are  characterized as having a later onset of disease, lower risk of  bleeding, and reduced requirements for factor VIII or factor IX  treatment as part of their disease management. There exists a  significant need for novel therapeutics to treat hemophilia and RBD.

About Antithrombin (AT)

Antithrombin (AT, also known as “antithrombin III” and “SERPINC1”) is a  liver expressed plasma protein and member of the “serpin” family of  proteins that acts as an important endogenous anticoagulant by  inactivating factor Xa and thrombin. AT plays a key role in normal  hemostasis, which has evolved to balance the need to control blood loss  through clotting with the need to prevent pathologic thrombosis through  anticoagulation. In hemophilia, the loss of certain procoagulant factors  (Factor VIII and Factor IX, in the case of hemophilia A and B,  respectively) results in an imbalance of the hemostatic system toward a  bleeding phenotype. In contrast, in thrombophilia (e.g., factor V  Leiden, protein C deficiency, antithrombin deficiency, amongst others),  certain mutations result in an imbalance in the hemostatic system toward  a thrombotic phenotype. Since co-inheritance of prothrombotic mutations  may ameliorate the clinical phenotype in hemophilia, inhibition of AT  defines a novel strategy for improving hemostasis.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a  breakthrough in understanding how genes are turned on and off in cells,  and a completely new approach to drug discovery and development. Its  discovery has been heralded as “a major scientific breakthrough that  happens once every decade or so,” and represents one of the most  promising and rapidly advancing frontiers in biology and drug discovery  today which was awarded the 2006 Nobel Prize for Physiology or Medicine.  RNAi is a natural process of gene silencing that occurs in organisms  ranging from plants to mammals. By harnessing the natural biological  process of RNAi occurring in our cells, the creation of a major new  class of medicines, known as RNAi therapeutics, is on the horizon. Small  interfering RNA (siRNA), the molecules that mediate RNAi and comprise  Alnylam’s RNAi therapeutic platform, target the cause of diseases by  potently silencing specific mRNAs, thereby preventing disease-causing  proteins from being made. RNAi therapeutics have the potential to treat  disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics  based on RNA interference, or RNAi. The company is leading the  translation of RNAi as a new class of innovative medicines with a core  focus on RNAi therapeutics toward genetically defined targets for the  treatment of serious, life-threatening diseases with limited treatment  options for patients and their caregivers. These include: ALN-TTR02, an  intravenously delivered RNAi therapeutic targeting transthyretin (TTR)  for the treatment of TTR-mediated amyloidosis (ATTR) in patients with  familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously  delivered RNAi therapeutic targeting TTR for the treatment of ATTR in  patients with familial amyloidotic cardiomyopathy (FAC); ALN-AT3, an  RNAi therapeutic targeting antithrombin (AT) for the treatment of  hemophilia and rare bleeding disorders (RBD); ALN-AS1, an RNAi  therapeutic targeting aminolevulinate synthase-1 (ALAS-1) for the  treatment of porphyria including acute intermittent porphyria (AIP);  ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of  hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for  the treatment of beta-thalassemia and iron-overload disorders; ALN-AAT,  an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for the  treatment of AAT deficiency liver disease; and ALN-CC5, an RNAi  therapeutic targeting complement component C5 for the treatment of  complement-mediated diseases, amongst other programs. As part of its   “Alnylam 5×15TM” strategy, the company expects to have five  RNAi therapeutic products for genetically defined diseases in clinical  development, including programs in advanced stages, on its own or with a  partner by the end of 2015. Alnylam has additional partnered programs in  clinical or development stages, including ALN-RSV01 for the treatment of  respiratory syncytial virus (RSV) infection and ALN-VSP for the  treatment of liver cancers. The company’s leadership position on RNAi  therapeutics and intellectual property have enabled it to form major  alliances with leading companies including Merck, Medtronic, Novartis,  Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, Cubist, Ascletis,  Monsanto, Genzyme, and The Medicines Company. In addition, Alnylam holds  an equity position in Regulus Therapeutics Inc., a company focused on  discovery, development, and commercialization of microRNA therapeutics.  Alnylam has also formed Alnylam Biotherapeutics, a division of the  company focused on the development of RNAi technologies for applications  in biologics manufacturing, including recombinant proteins and  monoclonal antibodies. Alnylam’s VaxiRNA™ platform applies RNAi  technology to improve the manufacturing processes for vaccines;  GlaxoSmithKline is a collaborator in this effort. Alnylam scientists and  collaborators have published their research on RNAi therapeutics in over  100 peer-reviewed papers, including many in the world’s top scientific  journals such as Nature, Nature Medicine, Nature  Biotechnology, and Cell. Founded in 2002, Alnylam maintains  headquarters in Cambridge, Massachusetts. For more information, please  visit

About “Alnylam 5×15™”

The “Alnylam 5×15” strategy, launched in January 2011, establishes a  path for development and commercialization of novel RNAi therapeutics  toward genetically defined targets for the treatment of diseases with  high unmet medical need. Products arising from this initiative share  several key characteristics including: a genetically defined target and  disease; the potential to have a major impact in a high unmet need  population; the ability to leverage the existing Alnylam RNAi delivery  platform; the opportunity to monitor an early biomarker in Phase I  clinical trials for human proof of concept; and the existence of  clinically relevant endpoints for the filing of a new drug application  (NDA) with a focused patient database and possible accelerated paths for  commercialization. By the end of 2015, the company expects to have five  such RNAi therapeutic programs in clinical development, including  programs in advanced stages, on its own or with a partner. The “Alnylam  5×15” programs include: ALN-TTR02, an intravenously delivered RNAi  therapeutic targeting transthyretin (TTR) for the treatment of  TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic  polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi  therapeutic targeting TTR for the treatment of ATTR in patients with  familial amyloidotic cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic  targeting antithrombin (AT) for the treatment of hemophilia and rare  bleeding disorders (RBD); ALN-AS1, an RNAi therapeutic targeting  aminolevulinate synthase-1 (ALAS-1) for the treatment of porphyria  including acute intermittent porphyria (AIP); ALN-PCS, an RNAi  therapeutic targeting PCSK9 for the treatment of hypercholesterolemia;  ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of  beta-thalassemia and iron-overload disorders; ALN-AAT, an RNAi  therapeutic targeting alpha-1-antitrypsin (AAT) for the treatment of AAT  deficiency liver disease; and ALN-CC5, an RNAi therapeutic targeting  complement component C5 for the treatment of complement-mediated  diseases, amongst other programs. Alnylam intends to focus on developing  and commercializing certain programs from this product strategy itself  in North and South America, Europe, and other parts of the world; these  include ALN-TTR, ALN-AT3, ALN-AS1, and ALN-CC5.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future  expectations, plans and prospects, including without limitation,  Alnylam’s expectations regarding its “Alnylam 5×15” product strategy,  Alnylam’s views with respect to the potential for RNAi therapeutics,  including ALN-AT3 for the treatment of hemophilia and Rare Bleeding  Disorders, its expectations with respect to the timing and success of  its clinical and pre-clinical trials, the expected timing of regulatory  filings, including its plan to file an IND application and initiate  clinical trials for ALN-AT3, its plans to seek a partner for certain   ‘Alnylam 5×15’ programs, and its plans regarding commercialization of  RNAi therapeutics, constitute forward-looking statements for the  purposes of the safe harbor provisions under The Private Securities  Litigation Reform Act of 1995. Actual results may differ materially from  those indicated by these forward-looking statements as a result of  various important factors, including, without limitation, Alnylam’s  ability to manage operating expenses, Alnylam’s ability to discover and  develop novel drug candidates and delivery approaches, successfully  demonstrate the efficacy and safety of its drug candidates, the  pre-clinical and clinical results for its product candidates, which may  not support further development of product candidates, actions of  regulatory agencies, which may affect the initiation, timing and  progress of clinical trials, obtaining, maintaining and protecting  intellectual property, Alnylam’s ability to enforce its patents against  infringers and defend its patent portfolio against challenges from third  parties, obtaining regulatory approval for products, competition from  others using technology similar to Alnylam’s and others developing  products for similar uses, Alnylam’s ability to obtain additional  funding to support its business activities and establish and maintain  strategic business alliances and new business initiatives, Alnylam’s  dependence on third parties for development, manufacture, marketing,  sales and distribution of products, the outcome of litigation, and  unexpected expenditures, as well as those risks more fully discussed in  the “Risk Factors” filed with Alnylam’s current report on Form 10-Q  filed with the Securities and Exchange Commission (SEC) on August 9,  2013 and in other filings that Alnylam makes with the SEC. In addition,  any forward-looking statements represent Alnylam’s views only as of  today and should not be relied upon as representing its views as of any  subsequent date. Alnylam explicitly disclaims any obligation to update  any forward-looking statements.

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton,
Vice President, Investor Relations and Corporate Communications
Spectrum Amanda Sellers (Media),
202-955-6222 x2597
For Press Release, Click here

First phase III trial of Novo Nordisk’s hemophilia drug complete

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Denmark’s Novo Nordisk, the world’s biggest insulin producer, said on Friday it had completed the first phase III trial of a hemophilia drug, N9-GP.

Bagsværd, Denmark, 17 May 2013 – Novo Nordisk today announced the completion of paradigm™ 2, the first phase 3 trial with a long-acting FIX derivative, N9-GP (glycopegylated recombinant factor IX), for haemophilia B patients. Paradigm™ 2 is a multi-centre, blinded trial evaluating the safety and efficacy of N9-GP when used for on- demand or prophylactic treatment in patients with haemophilia B.
In the trial, 74 patients were treated for six months on-demand, or 12 months by a prophylactic regimen of 40 U/kg or 10 U/kg N9-GP once weekly. The median bleeding rate for patients treated on-demand was 15.6 episodes per year. Patients on prophylaxis had a median annualised bleeding rate of 1.0 and 2.9 episodes per year, when treated with weekly doses of 40 U/kg and 10 U/kg, respectively.

Among patients randomised to receive 40 U/kg N9-GP, 99% of bleeding episodes were treated with only one infusion, and two-thirds of the patients experienced complete resolution of bleeding in their target joints. Patients in this dose group also reported an improvement in quality of life during the trial.

Pharmacokinetic data documented a steady state half-life of 110 hours.

In the trial, N9-GP appeared to have a safe and well-tolerated profile. No patients in the trial developed inhibitors, and no apparent differences between the treatment groups were observed with respect to adverse events and standard safety parameters.

“We are very excited about the strong results from this trial, which could represent a paradigm shift in the treatment of haemophilia B,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. ”The trial demonstrated that once-weekly prophylactic administration of N9-GP can reduce the risk of bleeds by more than 90% compared to on-demand treatment and enable 99% of the few occurring bleeds to be stopped with a single dose.”

Novo Nordisk is expecting the two remaining phase 3 trials in the paradigm™ programme involving paediatric patients and patients undergoing surgery respectively to be completed within the next 12 months. Regulatory submission of N9-GP in all major markets is expected in 2015 to enable validation of the commercial scale production.

About N9-GP and paradigm™  N9-GP is a proprietary glycopegylated recombinant factor IX for patients with haemophilia B. Glycopegylation is a well-established protraction technology applied by Novo Nordisk on recombinant factor IX. The technology increases the circulating half-life of recombinant factor IX allowing for lower bleeding frequency with less frequent intra- venous dosing.
The paradigm™ programme is a Novo Nordisk registered trademark for trial conducted with N9-GP. The programme currently comprises seven clinical trials investigating pharmacokinetics, immunogenicity, efficacy and safety of N9-GP in adult and paediatric haemophilia B patients as well as in patients undergoing surgery.

Novo Nordisk is a global healthcare company with 90 years of innovation and leadership in diabetes care. The company also has leading positions within haemophilia care, growth hormone therapy and hormone replacement therapy. Headquartered in Denmark, Novo Nordisk employs approximately 35,000 employees in 75 countries, and markets its products in more than 180 countries. Novo Nordisk’s B shares are listed on NASDAQ OMX Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO).

Further information
Mike Rulis +45 3079 3573
Ken Inchausti (US) +1 609 514 8316
Kasper Roseeuw Poulsen +45 4442 4303
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For information on the Clinical Trial, click here.

Bayer Provides Update on Phase II/III Trial of BAY 86-6150

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Berlin, May 3, 2013 – Bayer HealthCare today announced that a Phase II/III  trial evaluating the efficacy and safety of BAY 86-6150 in people with  hemophilia A and hemophilia B with inhibitors has been discontinued. The hope  that BAY 86-6150 might help patients with inhibitors to achieve better control  of their disease could not be fulfilled due to the detection of a neutralizing  antibody in the trial.

“Patient safety is our primary concern when designing clinical trials and  evaluating BAY 86-6150,” said Kemal Malik, MD, member of the Bayer HealthCare  Executive Committee and Head of Global Development. “Due to safety concerns, we  are discontinuing the BAY 86-6150 trial as a precautionary measure.”

About the Phase II/III Trial
The TRUST (TReatment with Unique recombinant rFVIIa STudy) trial is a Phase  II/III, multicenter, open-label clinical study designed to assess the safety  and efficacy of BAY 86-6150, a recombinant factor VIIa (rFVIIa) protein, in  patients with hemophilia A or B with inhibitors.

About Hemophilia A, Hemophilia B, and Inhibitors
Hemophilia A, also known as factor VIII deficiency or classic hemophilia, is  largely an inherited bleeding disorder in which one of the proteins needed to  form blood clots in the body is missing or reduced. Hemophilia A, the most  common type of hemophilia, is caused by a deficient or defective blood  coagulation protein, known as factor VIII. Hemophilia A is characterized by  prolonged or spontaneous bleeding, especially into the muscles, joints, or  internal organs.

Hemophilia B, also known as Christmas disease, is a less common type of  hemophilia.  People with hemophilia B have little or no factor IX.

Inhibitor development is a serious medical problem that can occur when a person  with hemophilia has an immune response to treatment with clotting factor  concentrates. About a third of hemophilia A patients develop inhibitors, with
the development of inhibitors being more common in hemophilia A.

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of  health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup  of Bayer AG with annual sales of EUR 18.6 billion (2012), is one of the world’s  leading, innovative companies in the healthcare and medical products industry  and is based in Leverkusen, Germany. The company combines the global activities  of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals  divisions. Bayer HealthCare’s aim is to discover, develop, manufacture and  market products that will improve human and animal health worldwide. Bayer  HealthCare has a global workforce of 55,300 employees (Dec 31, 2012) and is  represented in more than 100 countries. More information at

Forward-looking statements
This release may contain forward-looking statements based on current  assumptions and forecasts made by Bayer Group or subgroup management. Various  known and unknown risks, uncertainties and other factors could lead to material  differences between the actual future results, financial situation, development  or performance of the company and the estimates given here. These factors  include those discussed in Bayer’s public reports which are available on the  Bayer website at The company assumes no liability whatsoever to  update these forward-looking statements or to conform them to future events or  developments.

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