Baxter Provides Progress Update on Gene Therapy Program, Including Phase I/II Clinical Trial of BAX 335, Investigational Gene Therapy for Hemophilia B

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DEERFIELD, Ill., FEBRUARY 12, 2015 – Baxter International Inc. (NYSE:BAX) today provided an update on its gene therapy program, including progress on the Phase I/II open-label clinical trial assessing the safety and optimal dosing level of BAX 335, an investigational factor IX (FIX) gene therapy treatment for hemophilia B, during a sponsored symposium at the 8th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) in Helsinki, Finland.

The trial is assessing the safety of ascending doses of BAX 335 to determine the optimal single dose in up to 16 adult patients with hemophilia B at treatment centers in the United States. The primary endpoint is the safety of a single dose of BAX 335 administered intravenously. Secondary endpoints include evaluation of the optimal dose to achieve stable therapeutic plasma FIX activity, as well as pharmacokinetics and immune response to treatment.

As of the end of 2014, a total of six patients in three dosing cohorts have been treated in the trial with evidence of a dose-related response. No patients have developed FIX inhibitors to date. In the two highest dose cohorts, FIX activity levels around 10 percent or above have been observed in two patients, who also experienced no bleeding events. One of these patients showed elevated levels of liver enzymes indicative of an immune response, which is being treated with oral corticosteroids, per protocol. Immune responses have been reported in previous studies with gene therapy technology. Additional patients are being screened and more information on the trial is available at www.clinicaltrials.gov , by using Identifier #01687608.

“We continue to make steady progress in advancing our hemophilia B program with this technology and look forward to better understanding the applicability of this technology platform in hemophilia A patients as well,” said John Orloff, MD, vice president and global head of research and development at Baxter BioScience. “With the potential to redefine the treatment of hemophilia, this gene therapy technology is a central part of our R&D focus as we prepare to become an independent company this year,”

Patients with hemophilia B lack the ability to produce clotting factor IX and are treated with plasma-derived or recombinant factor IX today. BAX 335 is designed to provide a mechanism for the patient’s own liver to begin producing factor IX over an extended period following a single dose of the genetically engineered treatment.

In April 2014, Baxter announced the acquisition of Chatham Therapeutics, LLC, an affiliate of Asklepios BioPharmaceutical, Inc. (AskBio), and its developmental gene therapy programs. Chatham’s Biological Nano Particles (BNP), an advanced recombinant adeno-associated virus- (rAAV-) based gene therapy technology, has shown potential therapeutic benefit in early studies. In addition to the research in hemophilia B, Baxter is also advancing plans to evaluate the gene therapy technology in the treatment of hemophilia A.

About Hemophilia B
Hemophilia B is the second most common type of hemophilia (also known as Christmas disease) and is the result of insufficient amounts of clotting factor IX, a naturally occurring protein in blood that controls bleeding. Approximately 26,000 people worldwide, including more than 4,000 in the U.S., have been diagnosed with hemophilia B. Hemophilia B is often a debilitating, chronic disease with complications that include bleeding episodes, hemophilic arthropathy (bleeding into a joint) and hospitalization.

About Baxter in Hemophilia
Baxter has more than 60 years of scientific experience in supporting the treatment needs of patients with hemophilia and has introduced a number of therapeutic firsts. Baxter has the broadest portfolio of hemophilia treatments and is able to meet individualized patient therapeutic needs by providing a range of options at each treatment stage. The company’s work focuses on optimizing hemophilia care and improving the lives of people worldwide living with bleeding disorders.

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.

This release includes forward-looking statements concerning a Phase I/II open-label clinical trial of BAX 335, as well as plans to separate Baxter’s biopharmaceutical and medical products businesses and related research and development strategies. These statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: clinical trial results; satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; product quality or patient safety issues; and other risks identified in Baxter’s most recent filing on Form 10-K and other SEC filings, all of which are available on Baxter’s website.Baxter does not undertake to update its forward-looking statements.

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Weekly prophylaxis with nonacog beta pegol safe, effective for hemophilia B

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Collins PW. Blood. 2014;doi:10.1182/blood-2014-05-573055.

Nonacog beta pegol effectively treated bleeding episodes and was associated with low annualized bleeding rates in patients with hemophilia B, according to study results.

From www.healio.com October 31, 2014

Peter W. Collins, MD, of the Arthur Bloom Hemophilia Center at Cardiff University in the United Kingdom, and colleagues sought to evaluate the safety and efficacy of nonacog beta pegol (N9-GP, Novo Nordisk) — a recombinant glycoPEGylated Factor IX with an extended half-life — in 74 previously treated patients with hemophilia B.

Thirty patients received with 10 IU/kg weekly for 52 weeks, and 29 patients received 40 IU/kg weekly for 52 weeks. The other 15 patients received on-demand treatment for 28 weeks.

The mean number of exposure days was 54 days in the weekly prophylaxis arms and 14 days in the on-demand arm.

Fifty-five patients (74%) experienced a combined 345 bleeding episodes; of these, 202 occurred in the weekly prophylaxis arms and 143 occurred in the on-demand treatment arm. Most bleeding episodes (78.5%) occurred in joints. Researchers classified 65.8% episodes as spontaneous and 33.6% as traumatic.

Researchers calculated a 92.2% (95% CI, 86.9-95.4) success rate for treating bleeding episodes. A greater proportion of bleeding episodes resolved after one injection of nonacog beta pegol in the 40 IU/kg arm (98.6%) than in the 10 IU/kg arm (84.1%) and the on-demand treatment arm (83.9%).

Fifty-two percent of patients in the 40 IU/kg arm did not require treatment for any bleeding episodes, compared with 17% of patients in the 10 IU/kg arm and 7% of patients in the on-demand arm. The median annualized bleeding rate also was lower in the 40 IU/kg arm (1.04; interquartile range [IQR], 0-4) than in the 10 IU/kg arm (2.93; IQR, 0.99-6.02) and the on-demand arm (15.58; IQR, 9.56-26.47).

Researchers used the EuroQOL-5 Dimensions visual analogue scale to assess health-related quality of life in each study arm. Patients in the 40 IU/kg arm experienced the greatest improvements in quality of life, from a median score of 75 (range, 35-100) at baseline to 90 (range, 60-100) at the end of the trial.

Sixty patients (81%) experienced a combined 215 adverse events. The most commonly reported adverse events were nasopharyngitis (13.5%), influenza (10.8%) and upper respiratory tract infection (10.8%).

No patients developed an inhibitor, and researchers reported no deaths, thromboembolic events or allergic reactions related to treatment.

“Nonacog beta pegol was effective for the treatment of bleeding episodes in both prophylaxis and on-demand patients,” Collins and colleagues wrote. “Low bleeding rates were observed in patients on prophylaxis and are likely related to high trough levels due to the extended half-life of nonacog beta pegol. These data suggest that once-weekly prophylaxis with nonacog beta pegol may provide a new and safe alternative for the prevention and treatment of bleeding episodes in patients with Hemophilia B.”

Disclosure: The study was funded in part by Novo Nordisk A/S. The researchers report honoraria and research funding from, advisory/consultant roles with and employment with Baxter, Bayer, Biogen Idec, CSL Behring, Grifols, LFB, Novo Nordisk, Octapharma, Pfizer, Sanquin and Swedish Orphan Biovitrum.

Gene therapy found effective in hemophilia B

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(Reuters Health) – Ten patients with severe hemophilia B have remained cured of the inherited bleeding disorder for as long as three years thanks to gene therapy, according to a new report on the technique in the New England Journal of Medicine.

The study updates an earlier one from 2011, in which six volunteers were successfully treated with various doses of the treatment that uses a virus to insert genetic material into the liver. The four additional patients received the highest dose.

“I believe that, scientifically, this is ready for prime time,” the chief author, Dr. Andrew Davidoff of St. Jude Children’s Research Hospital in Memphis, Tennessee, told Reuters Health in a telephone interview.

The problem, he said, is that the genetically engineered virus that delivers the cure “is really a bear to make” and better methods to produce the treatment are desperately needed. To engineer enough virus to treat the 10 patients required six months of work.

Davidoff and his colleagues found that the higher the dose of the engineered virus, the more factor IX the body produced. Factor IX is a protein crucial to blood clotting and is defective in hemophilia B patients.

The researchers used an adeno-associated virus or AAV, which infects the liver without causing apparent illness.

The therapy seemed to have no serious side effects and is designed to eliminate the need to give patients injections of factor IX every two or three days at a cost of about $250,000 per year.

The treatment produced factor IX levels in a range of 1 percent to 6 percent of normal. But even a few percentage points can be enough to prevent dangerous bleeding. A single infusion was sufficient.

For the six high-dose recipients, the factor IX level averaged 5.1 percent, “which resulted in a reduction of more than 90 percent in both bleeding episodes and the use of prophylactic factor IX concentrate,” the research team wrote.

“I think it’s going to have a big impact. The study showed both safety and efficacy and the side effects were minimal,” said Dr. Timothy Nichols, who heads the Francis Owen Blood Research Laboratory at the University of North Carolina and was not involved in the study.

“This is a single shot of medicine given to patients who are treating themselves two or three times a week,” he told Reuters Health by phone. “Suddenly, they don’t have to take the medicine anymore.”

Worldwide, about 1 in 25,000 men are born with hemophilia B each year. It is less common than hemophilia A, which is caused by a problem with a different protein and affects about 1 in 5,000 men.

Because the genetic code for the clotting factors is carried on the X chromosome, and males don’t have a backup copy of that chromosome as women do, the condition is almost exclusively a disease of men.

Nichols said most people with hemophilia would be “very eager to consider the treatment and move forward if production issues can be resolved.”

“Hopefully (the new results) will be a catalyst for us and others to find a more effective way to produce AAV,” Davidoff said. “In fact, we’re in discussions with other companies in terms of investing in our research for improving production.”

SOURCE: bit.ly/1t6duWb New England Journal of Medicine, online November 19, 2014.

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Click links for other articles about this study – medicalxpress.com
ScienceDaily.com
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Recombinant long-acting glycoPEGylated factor IX in hemophilia B

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a multinational randomized phase 3 trial

Peter W. Collins1,*, Guy Young2, Karin Knobe3, Faraizah Abdul Karim4, Pantep Angchaisuksiri5, Claus Banner6, Türkiz Gürsel7, Johnny Mahlangu8, Tadashi Matsushita9, Eveline P. Mauser-Bunschoten10, Johannes Oldenburg11 Christopher E. Walsh12, and Claude Negrier13

Key points

  • Nonacog beta pegol, a recombinant glycoPEGylated FIX with extended half-life, was developed to improve care for hemophilia B patients.

  • Weekly prophylaxis with nonacog beta pegol was well tolerated and associated with low bleeding rates and an improved quality of life.

Abstract

This multinational, randomized, single-blind trial (NCT01333111 [www.clinicaltrials.gov]) investigated safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in 74 previously treated hemophilia B patients (FIX activity ≤2 IU/dL). Patients received prophylaxis for 52 weeks, randomized to 10 IU/kg or 40 IU/kg once weekly, or on-demand treatment for 28 weeks. No patients developed inhibitors and no safety concerns were identified. Three-hundred and forty-five bleeding episodes were treated with an estimated success rate of 92.2%. The median annualized bleeding rates (ABRs) were 1.04 in the 40 IU/kg prophylaxis arm, 2.93 in the 10 IU/kg prophylaxis arm, and 15.58 in the on-demand treatment arm. In the 40 IU/kg arm, 10 of 15 patients (66.7%) experienced no bleeding episodes into target joints, compared with 1 of 13 patients (7.7%) in the 10 IU/kg arm. Health-related quality of life (HR-QoL) assessed with the EQ-5D VAS score improved from median 75 to 90 in the 40 IU/kg prophylaxis arm. Nonacog beta pegol was well tolerated and efficacious for treatment of bleeding episodes, and associated with low ABRs in patients on prophylaxis. Once-weekly prophylaxis with 40 IU/kg resolved target joint bleeds in 66.7% of the affected patients and improved HR-QoL.

Another article can be found below….

Bleeding episodes were effectively treated by nonacog beta pegol and was associated with low annualized bleeding rates in hemophilia B patients, according to a study published in Blood, shown above.
Researchers from the Arthur Bloom Hemophilia Center at Cardiff University in the United Kingdom examined 74 hemophilia patients which had been previously treated in order to evaluate the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX with an extended half-life. The patients were divided into 3 groups: 30 patients received weekly prophylaxis 10 IU/kg for 52 weeks; 29 patients received weekly prophylaxis 40 IU/kg for 52 weeks; and 15 patients received on-demand treatment for 28 weeks. Patients receiving weekly treatment averaged 54 exposure days, while the on-demand treatment group averaged 14 days.

The investigators identified 345 bleeding episodes which came from 55 patients (74 percent). A third of the episodes were classified by researchers as traumatic (33.6 percent) while the remaining 65.8 percent of episodes were considered spontaneous. More than half (202 episodes) came from the weekly prophylaxis group and 143 came from the on-demand treatment group. A majority (78.5 percent) of the bleeding episodes occurred in joints.

Successful treatment of bleeding episodes was calculated to be 92.2 percent. More episodes were resolved after 1 injection of nonacog beta pegol in the weekly 40 IU/kg group (98.6 percent) than in the weekly 10 IU/kg group (84.1 percent). The on-demand treatment group was 83.9 percent successful in controlling bleeding episodes.

Half of the patients (52 percent) in the weekly 40 IU/kg treatment group did not require any treatment from the bleeding episodes, while 17 percent and 7 percent in the weekly 10 IU/kg and on-demand treatment groups, respectively, did not require treatment. Researchers pointed out the annualized bleeding rate was lower in the weekly 40 IU/kg treatment group, than in the weekly 10 IU/kg and on-demand treatment groups.

Researchers determined the weekly 40 IU/kg treatment group experienced the greatest improvements in quality of life, based on baseline scores of about 75 to 90 by the end of the trial on the EuroQOL-5 Dimensions scale.

Adverse events were experienced by 60 patients (81 percent) for a combined 215 events. Most commonly, these adverse events were nasopharyngitis (13.5 percent), influenza (10.8 percent), and upper respiratory tract infection (10.8 percent). The researchers noted no patients developed an inhibitor. They also noted there were no deaths, thromboembolic events, or allergic reactions to the treatment.

“Nonacog beta pegol was effective for the treatment of bleeding episodes in both prophylaxis and on-demand patients,” Peter W. Collins, MD, and colleagues concluded. “Low bleeding rates were observed in patients on prophylaxis and are likely related to high trough levels due to the extended half-life of nonacog beta pegol. These data suggest that once-weekly prophylaxis with nonacog beta pegol may provide a new and safe alternative for the prevention and treatment of bleeding episodes in patients with hemophilia B.” – See more at: http://www.hcplive.com/publications/hemophilia-reports/2014/october2014/Treatment-for-Hemophilia-B-Patients-Is-Effective-Well-Tolerated#sthash.qGMJCrha.dpuf

FDA Approves Baxter’s RIXUBIS [Coagulation Factor IX (Recombinant)] for Treatment of Children with Hemophilia B

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Approval Based on Clinical Data Finding 39% of Pediatric Patients Less Than 12 Years of Age Experienced No Bleeds on Prophylactic Treatment

DEERFIELD, Ill., September 15, 2014 – Baxter International Inc. (NYSE:BAX) today announced that the United States Food and Drug Administration (FDA) has approved RIXUBIS [Coagulation Factor IX (Recombinant)] for routine prophylactic treatment, control and prevention of bleeding episodes, and perioperative management in children with hemophilia B. RIXUBIS was the first recombinant factor IX (rFIX) approved for routine prophylaxis and control of bleeding episodes in the U.S. for adults living with this chronic condition.

“In addition to the positive reception we’ve received from adult RIXUBIS patients, the approval for pediatric patients offers a valuable new option, particularly as our clinical data demonstrated a significant reduction in bleeding episodes for patients who were treated prophylactically, an important factor for this young patient population,” said John Orloff, M.D., vice president of global research and development at Baxter BioScience.

The approval is based on the results of a clinical trial investigating the efficacy and safety of RIXUBIS among 23 previously-treated male patients less than
12 years of age with severe or moderately severe hemophilia B. The patients were treated with a twice-weekly RIXUBIS prophylaxis regimen (mean dose
56 IU/kg) for a mean treatment duration of six months and a mean of 54 exposure days (EDs). The median annualized bleeding rate (ABR) was 2.0 (0.0 for spontaneous bleeds and joint bleeds). Nine patients in the study (39.1%) experienced no bleeds and 23 bleeding episodes (88.5%) were treated with 1-2 infusions. There were no reports of inhibitor development, no severe allergic reactions, and no thrombotic or treatment-related adverse events among the study participants. Common adverse reactions observed in >1% of subjects in clinical studies were dysgeusia, pain in extremity, and positive test for furin antibody. These data were presented during the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, LA.

Baxter’s application for marketing approval for RIXUBIS for adults and pediatric patients is currently under review in the European Union, with a regulatory decision expected later this year. The treatment also recently gained regulatory approval in Australia.

About RIXUBIS
RIXUBIS [Coagulation Factor IX (Recombinant)] is an antihemophilic factor indicated in adults and children with hemophilia B for control and prevention of bleeding episodes, perioperative management, and routine prophylaxis. RIXUBIS is not indicated for induction of immune tolerance in patients with hemophilia B.

RIXUBIS was the first rFIX approved by the FDA for both routine prophylaxis and control of bleeding episodes in adults with this chronic condition.

Important Risk Information for RIXUBIS

CONTRAINDICATIONS
RIXUBIS is contraindicated in patients who have:

  • Known hypersensitivity to RIXUBIS or its excipients including hamster protein
  • Disseminated Intravascular Coagulation (DIC)
  • Signs of fibrinolysis


WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions
Hypersensitivity reactions (including symptoms such as dyspnea and pruritus) have been reported with RIXUBIS. Anaphylaxis and other hypersensitivity reactions are possible. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest tightness, hypotension, lethargy, nausea, vomiting, paresthesia, urticaria, rash, restlessness, wheezing, and dyspnea. Immediately discontinue administration and initiate appropriate treatment if allergic- or anaphylactic-type reactions occur.

Inhibitors
Development of neutralizing antibodies (inhibitors) to factor IX may occur. Regularly evaluate patients for the development of factor IX inhibitors by appropriate clinical observations and laboratory tests. If expected factor IX plasma activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor IX inhibitor concentration. Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to RIXUBIS.

Nephrotic Syndrome
Nephrotic syndrome has been reported following attempted immune tolerance induction with factor IX products in hemophilia B patients that have factor IX inhibitors. The safety and efficacy of using RIXUBIS for immune tolerance induction have not been established.

Thromboembolic Complications
The use of factor IX containing products has been associated with the development of thromboembolic complications. Monitor patients for early signs of thromboembolic and consumptive coagulopathy, when administering RIXUBIS to patients with liver disease, with signs of fibrinolysis, peri- and post-operatively, or at risk for thromboembolic events or DIC.

ADVERSE REACTIONS
Common adverse reactions observed in >1% of subjects in clinical studies were: dysgeusia, pain in extremity, and positive test for furin antibody.

Post-marketing Experience
The following class adverse reactions have been seen with another recombinant factor IX: inadequate factor IX recovery, inhibitor development, anaphylaxis, angioedema, hypotension, and thrombosis.

About Hemophilia B
Hemophilia B is the second most common type of hemophilia (also known as Christmas disease) and is the result of insufficient amounts of clotting factor IX, a naturally occurring protein in blood that controls bleeding.1 Approximately 26,000 people worldwide, including more than 4,000 in the U.S., have been diagnosed with hemophilia B.2 Hemophilia B is often a debilitating, chronic disease with complications that include bleeding episodes, hemophilic arthropathy (bleeding into a joint) and hospitalization.3

About Baxter in Hemophilia
Baxter has more than 60 years experience in hemophilia and has introduced a number of therapeutic firsts for hemophilia patients. The company has the broadest portfolio of hemophilia treatments in the industry and is able to meet individual therapy choices, providing a range of options at each treatment stage. The company’s work is focused on optimizing hemophilia care and improving the lives of people living with hemophilia A and B worldwide. Its diverse pipeline includes longer-acting therapies for hemophilia A, potential new treatments for hemophilia B (including gene therapy), von Willebrand disease and a recombinant treatment for patients with inhibitors.

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.

This release includes forward-looking statements concerning RIXUBIS, including expectations with regard to regulatory filings. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; additional clinical results; changes in laws and regulations; product quality or supply or patient safety issues; and other risks identified in Baxter’s most recent filing on Form 10-K and other SEC filings, all of which are available on Baxter’s website. Baxter does not undertake to update its forward-looking statements.

 

1Types of Bleeding Disorders: Hemophilia B. National Hemophilia Foundation. Accessed on May 10, 2013. Available at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=181&contentid=46&rptname=bleeding
22011 Annual Global Survey. World Federation of Hemophilia. Accessed on May 10, 2013. Available at: http://www1.wfh.org/publications/files/pdf-1488.pdf
3Lee-Rodríguez-Merchán, E.-C. and Valentino, L. A. (2011) New Developments in Hemophilic Arthropathy, in Current and Future Issues in Hemophilia Care (eds E.-C. Rodríguez-Merchán and L. A. Valentino), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781119979401.ch29

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Sangamo BioSciences Announces Target Date For First IND For Sangamo’s In Vivo ZFN Genome-Editing Platform For Monogenic Diseases

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Timeline for Hemophilia B IND Application Filing Targeting Second Quarter 2015

RICHMOND, Calif., Sept. 10, 2014 /PRNewswire/ — Sangamo BioSciences, Inc.  announced plans to submit an Investigational New Drug (IND) application for the treatment of hemophilia B in the second quarter of 2015.  This program, partnered with Shire, is the first therapeutic application of Sangamo’s zinc finger nuclease (ZFN)-mediated In Vivo Protein Replacement Platform (IVPRP). Sangamo is developing the IVPRP as a generally applicable strategy to provide a one-time, permanent genetic cure for monogenic diseases that are currently managed by protein replacement therapy, which involves costly repeat infusions over the lifetime of the patient.

“Shire has been impressed by the rapid progress of the novel hemophilia B program developed by Sangamo,” said Albert Seymour, Ph.D., Senior Vice President and Head of Global Research and Nonclinical Development at Shire.  “The Shire team continues to work very closely with Sangamo to submit the IND package to support this program.”

“Sangamo’s research and development team has succeeded in rapidly advancing the hemophilia B program through small and large animal proof of concept experiments, as well as pioneering manufacturing and regulatory pathways,” said Edward Lanphier, Sangamo’s president and CEO.  “I am very pleased with the progress that we and the new Shire team have made as we prepare to file an IND application for this first IVPRP program. Our experience with hemophilia B informs and supports our follow-on programs that leverage our IVPRP strategy, including our Shire-partnered program for the treatment of  hemophilia A and Sangamo’s proprietary programs in lysosomal storage disorders (LSDs).  With the success of these programs, going forward, it is our goal to develop and file two to four new INDs per year for the foreseeable future.”

“With the recent acceptance of an IND for mRNA delivery of ZFNs in Sangamo’s SB-728-T program, upcoming initiation of Phase 1 clinical testing of our hematopoietic stem-cell program for HIV (SB-728-HSC), and the unanimous approval of our Phase 1 ZFN Bcl11a program yesterday, at the NIH Recombinant Advisory Committee (RAC) meeting, keeping us on track to file an IND application for our beta-thalassemia program by the end of the year, we are realizing our goal of developing a new class of  human therapeutics that have the potential to provide genetic cures for a range of monogenic diseases and unmet medical needs,” added Mr. Lanphier.

“We are successfully forging a path to the clinic for Sangamo’s ZFN-based IVPRP,” said Geoff Nichol, M.B., Ch.B., Sangamo’s executive vice president of research and development.  “We have gained valuable expertise in clinical scale AAV manufacturing and the regulatory requirements for IND submissions of the hemophilia B and other IVPRP programs.  We are pleased to move forward with an IND package for our hemophilia B program which supports Shire’s IND requirements and, building on preclinical proof-of-concept data in our hemophilia A program, will implement a similar strategy as we bring that program to IND.  The proprietary LSD programs that Sangamo is developing based on this platform are also progressing well and on schedule.  Together, these assets are moving us rapidly towards the establishment of a ZFN-mediated platform for permanently treating protein and enzyme deficiency diseases and our long-term goal of initiating two to four new clinical programs per year.”

Sangamo is targeting an IND application filing for hemophilia A by year end 2015 and anticipates providing updated guidance of the IND timeline for this program by the end of the first quarter of 2015.  The two hemophilia programs are the first in a platform of IVPRP assets that use intravenous AAV-delivered ZFNs to target the albumin locus and drive permanent expression of therapeutic proteins for a wide range of deficiency diseases, including the hemophilias, LSDs and other metabolic diseases.

Background on Hemophilia A and B and Sangamo’s IVPRP Approach
Patients with hemophilia have a genetic mutation in the gene that encodes a blood-clotting factor (factor VIII in the case of hemophilia A, and factor IX in the case of hemophilia B), and, as a result, cannot make sufficient active factor VIII or IX protein to ensure efficient blood clotting. Sangamo’s IVPRP is designed to provide a one-time, potentially curative treatment for patients with monogenic diseases, such as hemophilia and LSDs, who currently require repeated infusions of protein replacement therapies throughout their lives.  The IVPRP approach enables the patient’s liver to permanently produce therapeutic levels of a corrective protein product such as factor VIII or IX to treat hemophilia, or replacement enzymes to treat LSDs.

The IVPRP approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site”, that can be edited with zinc finger nucleases (ZFNs) to accept and express any therapeutic gene. With such a large capacity for protein production (approximately 15g/day of albumin), which is in excess of the body’s requirements, targeting and co-opting only a very small percentage of the albumin gene’s capacity is sufficient to produce the needed replacement protein at therapeutically relevant levels with no significant effect on albumin production.

Pending acceptance of the IND application, a single intravenous infusion will be used to deliver adeno-associated viral (AAV) vectors encoding the ZFNs and a copy of a replacement gene used to correct the genetic defect. The zinc finger nucleases drive targeted, permanent insertion of a normal factor IX gene at the albumin locus in the liver cells of patients with hemophilia B.  This results in ongoing production of factor IX protein by the gene-edited liver cells under the control of the highly active albumin promoter.

About Sangamo
Sangamo BioSciences, Inc. is focused on Engineering Genetic Cures™ for monogenic and infectious diseases by deploying its novel DNA-binding protein technology platform in therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS (SB-728-T) and NGF-AAV for Alzheimer’s disease (CERE-110). Sangamo’s other therapeutic programs are focused on monogenic and rare diseases.  The company has formed a strategic collaboration with Shire International GmbH to develop therapeutics for hemophilia, Huntington’s disease and other monogenic diseases, and with Biogen Idec for hemoglobinopathies, such as sickle cell disease and beta-thalassemia. It has also established strategic partnerships with companies in non-therapeutic applications of its technology, including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the Company’s website at www.sangamo.com.

ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.

This press release may contain forward-looking statements based on Sangamo’s current expectations. These forward-looking statements include, without limitation, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo’s ZFP technology platform for the treatment of hemophilia B and other monogenic diseases, the timing of submissions of INDs for the treatment of hemophilia B, hemophilia A and lysosomal storage diseases, and the timing of submissions of INDs for other partnered programs and Sangamo proprietary programs. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo’s ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo’s public filings with the Securities and Exchange Commission, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

SOURCE Sangamo BioSciences, Inc.

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Pfizer Announces Positive Top-Line Results From Phase 3 Study Of NONACOG ALFA (BeneFIX®) Once-Weekly Prophylaxis For Hemophilia B

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Once-Weekly Prophylaxis Treatment with BeneFIX® Significantly Reduced Annualized Bleeding Rate Compared to On-Demand Treatment

Wednesday, July 16, 2014 – 7:00am EDT

Pfizer Inc. (NYSE:PFE) today announced the positive results of a Phase 3 study comparing a prophylaxis regimen of BeneFIX® Coagulation Factor IX (Recombinant) 100 IU/kg once-weekly to on-demand treatment in people with moderately severe to severe hemophilia B. The top-line results of the study showed that the primary study endpoint was met and hemophilia B patients taking once-weekly BeneFIX (100 IU/Kg) showed a statistically significant reduction in the annualized bleeding rate (ABR) (P < 0.0001) relative to on-demand treatment with BeneFIX.

In the study, the median ABR value, a commonly used measure of efficacy for prophylaxis regimens in hemophilia, was 2.0 for the prophylaxis regimen, compared to 33.6 for the on-demand regimen, representing a 94% decrease in bleeding rates. The mean ABR value was 3.6 for the prophylaxis period, compared to 32.9 for the on-demand treatment, which represents a reduction of 89% (P < 0.0001).

“These results are important because they add to the growing body of clinical evidence showing that prophylaxis treatment has the potential to reduce the number of bleeds in a year, the most critical factor in hemophilia management,” said Steven J. Romano, M.D., senior vice president and Medicines Development Group Head, Global Innovative Pharmaceuticals, Pfizer Inc. “Pfizer remains committed to the research and development of new and innovative products for the hemophilia community.”

Study results also showed that prophylaxis treatment significantly reduced both spontaneous and traumatic ABR compared to on-demand treatment with BeneFIX. The median spontaneous ABR value was 1.0 for the prophylaxis regimen, compared to 22.4 for the on-demand regimen, and the median traumatic ABR value was 1.0 for the prophylaxis period, compared to 4.1 for the on-demand treatment. In addition to meeting the primary endpoint, the secondary study endpoints showed that none of the 1,254 prophylaxis infusions administered during the study were associated with a less than expected therapeutic effect (LETE) occurrence, which was defined as a spontaneous bleed occurring within 48 hours of a prophylaxis infusion. The majority (82.1%) of bleeding episodes in the prophylaxis arm were resolved after one infusion.

Adverse events observed in the study, for both the prophylaxis and on-demand periods, were consistent with the known adverse event profile of BeneFIX. The most common adverse events reported during the prophylaxis treatment period were arthralgia (20%), upper respiratory infection (20%), toothache (20%), pyrexia (16%), headache (16%), pharyngitis (12%), back pain (12%) and local swelling (12%). No inhibitor development, thrombotic events or allergic reactions related to this product were observed in this study.

These results are preliminary, top-line data and are subject to additional analyses. Complete results from this study will be submitted for presentation at upcoming medical congresses and submitted for publication in a peer-reviewed journal.

Study Background

This study was a Phase 3, open-label, non-randomized two-period study consisting of six months of on-demand therapy only, followed by 12 months of routine prophylaxis with BeneFIX 100 IU/kg once-weekly. Participants included in this study were males with a mean age of 31.3 years (N=25) and moderately severe to severe hemophilia B (FIX:C ≤2%). Of the 25 participants enrolled in the study, all received at least one dose of study drug, and no participants discontinued treatment early. The mean duration of treatment was 550 days.

About BeneFIX

BeneFIX is a recombinant coagulation factor IX product indicated for the control, prevention and perioperative management of bleeding episodes in adult and pediatric patients with hemophilia B. BeneFIX received FDA approval in the U.S. on February 11, 1997, and was approved in the European Union later that year. It has been studied in clinical trials in both previously treated and untreated patients, and established in both on-demand and preventive care, additionally shown to help control bleeds in major and minor surgeries. BeneFIX is not approved for prophylaxis use in the United States.

BeneFIX Indications and Usage

BeneFIX is an injectable medicine that is used to help control and prevent bleeding in people with hemophilia B. Hemophilia B is also called congenital factor IX deficiency or Christmas disease.

BeneFIX is NOT used to treat hemophilia A.

Important Safety Information for BeneFIX

  • BeneFIX is contraindicated in patients who have manifested life-threatening, immediate hypersensitivity reactions, including anaphylaxis, to the product or its components, including hamster protein.
  • Call your health care provider right away if your bleeding is not controlled after using BeneFIX.
  • Allergic reactions may occur with BeneFIX. Call your health care provider or get emergency treatment right away if you have any of the following symptoms: wheezing, difficulty breathing, chest tightness, your lips and gums turning blue, fast heartbeat, facial swelling, faintness, rash or hives.
  • Your body can make antibodies, called “inhibitors,” which may interfere with the effectiveness of BeneFIX.
  • If you have risk factors for developing blood clots, such as a venous catheter through which BeneFIX is given by continuous infusion, BeneFIX may increase the risk of abnormal blood clots. The safety and efficacy of BeneFIX administration by continuous infusion have not been established.
  • Some common side effects of BeneFIX are nausea, injection site reaction, injection site pain, headache, dizziness and rash.

Please see full Prescribing Information for BeneFIX available at www.BeneFIX.com.

About Hemophilia

Hemophilia is a type of bleeding disorder that causes the blood to take a long time to clot as a result of a deficiency in one of several blood clotting factors, and occurs almost exclusively in males. People with hemophilia B have a deficiency in clotting factor IX, a specific protein in the blood. Hemophilia B is also called congenital factor IX deficiency or Christmas disease. People with hemophilia face specific risks and need to be careful not to cause injury to their bodies, as injuries can prompt a bleed, which have the potential to be life threatening.

Pfizer Inc.: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more, please visit us at www.pfizer.com.

Contact:

Media: Jennifer Kokell, (212) 733-2596
Investor: Ryan Crowe, (212) 733-8160

For original Press Release, Click here.

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