CSL Behring Receives FDA Orphan Drug Designation for rVIIa-FP

KING OF PRUSSIA, Pa., Feb. 16, 2012 /PRNewswire/ – CSL Behring announced today that the company has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for its novel recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP). The Orphan Drug Designation is granted for the treatment and prophylaxis of bleeding episodes in patients with congenital hemophilia and inhibitors to coagulation factor VIII or IX. CSL Behring is developing this therapy in collaboration with its parent company CSL Limited (ASX: CSL).

The CSL Behring rVIIa-FP clinical program will soon be initiated and intends to demonstrate that an extended half-life rVIIa-FP will result in a requirement for fewer doses while providing adequate therapeutic response in patients who have hemophilia A and B with inhibitors.

“CSL Behring’s albumin fusion technology uses albumin as the ideal recombinant genetic fusion partner for coagulation factor proteins because of its high tolerability, inherently long half-life, low potential for immunogenic reactions and known mechanism of clearance,” said Russell Basser, M.D., Senior Vice President, Global Clinical R&D at CSL Behring. “CSL Behring’s rVIIa albumin fusion protein is expected to exhibit a good tolerability profile and improved pharmacokinetics that may enable prophylaxis. We welcome Orphan Drug Designation for our rVIIa-FP and will work closely with the FDA to make this important therapy available for people in the U.S. with hemophilia A and hemophilia B with inhibitors.”

The FDA’s Orphan Drug Designation program provides orphan status to unique drugs and biologics, defined as those intended for the safe and effective treatment or prevention of rare diseases that affect fewer than 200,000 people in the U.S. Orphan designation qualifies the sponsor of the product for important tax credits, elimination of FDA license application fees and certain marketing incentives.

CSL Behring’s rVIIa-FP was granted Orphan Drug Designations (ODD) by the European Commission in May, 2011.

About Hemophilia
Hemophilia is a congenital bleeding disorder characterized by prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. In nearly all cases, it affects only males. The disease is caused by deficient or defective blood coagulation proteins known as factor VIII or IX. The most common form of the disease is hemophilia A, or classic hemophilia, in which the clotting factor VIII is either deficient or defective.  Hemophilia B is characterized by deficient or defective factor IX. Hemophilia A affects approximately 1 in 5,000 to 10,000 people. Hemophilia B affects approximately 1 in 25,000 to 50,000 people. The recommended treatment for patients who are factor deficient is to treat by replacement factor therapy. A complication in some patients is the development of inhibitory antibodies (inhibitors) to FVIII or FIX which renders replacement therapy ineffective.  This can occur in up to 25 percent of hemophilia A patients and around 5 percent of hemophilia B patients.  One treatment option for these patients is recombinant activated factor VII (called a bypassing agent) which can be used to achieve hemostasis without the need for factor VIII or IX. 

About the recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP)
Preclinical studies have confirmed that CSL Behring’s rVIIa-FP has favorable pharmacokinetic properties compared with the existing recombinant FVIIa product. Significant increases in half-life have been observed across all animal species. The use of a bypassing agent with an extended half-life could offer significant benefit to those affected by hemophilia A or B with inhibitors and may offer patients the opportunity to be treated less frequently than with currently available product.

About CSL Behring
CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide. CSL Behring therapies are indicated for the treatment of coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease. The company’s products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in newborns. CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited (ASX:CSL), a biopharmaceutical company headquartered in Melbourne, Australia. For more information, visit www.cslbehring.com.

For Press release click here.

SOURCE CSL Behring

Gene therapy proves effective for hemophilia B

SAN DIEGO | Sat Dec 10, 2011 3:42pm EST By Deena Beasley

(Reuters) – A single treatment with gene therapy, an experimental technique for fixing faulty genes, has been shown for the first time to boost output of a vital blood clotting factor, possibly offering a long-term solution for people with hemophilia B.

Researchers said the same technology was also being studied as a treatment for hemophilia A, the far more common type of the inherited bleeding disorder.

“It is a technique for potentially permanently curing patients,” said Dr. Charles Abrams, American Society of Hematology secretary and associate chief of hematology/oncology at the University of Pennsylvania in Philadelphia.

The strategy involves replacing the defective gene that causes the bleeding disorder with a correct version delivered via a virus to the patient’s liver cells — the only cells in the body capable of producing certain clotting factors missing or deficient in people with hemophilia.

The factors are numbered using Roman numerals. The two main forms of the disease are hemophilia A, caused by a lack of clotting factor VIII, and hemophilia B, caused by a lack of clotting factor IX.

Researchers from the University College London Cancer Institute and St. Jude Children’s Research Hospital in Memphis, Tennessee, studied six men with severe hemophilia B who were producing clotting factor IX, also called FIX, at less than 1 percent of normal levels. The general goal of current treatment with manufactured FIX is to achieve factor levels greater than 1 percent of normal.

Four of the six trial participants have stopped routine treatment and remain free of spontaneous bleeding. The other two have increased the interval between FIX infusions to once every 10 days to two weeks from two to three times a week, said Dr. Andrew Davidoff, chairman of the department of surgery at St. Jude’s and co-author of the study.

HIGH COST FOR CURRENT TREATMENT

Frequent treatments with manufactured FIX can cost hundreds of thousands of dollars a year, making hemophilia a tempting target for gene therapy.

The trial “is truly a landmark study,” Dr. Katherine Ponder, hematology and oncology professor at Washington University in St. Louis, said in a New England Journal of Medicine editorial.

“If further studies determine that this approach is safe, it may replace the cumbersome and expensive protein therapy currently used for patients with hemophilia B,” she wrote.

The trial results were published in the NEJM and reported on Saturday at a meeting of the American Society of Hematology in San Diego.

The approach involved the use of a novel viral “vector,” designed to target the liver specifically.

The six trial subjects were broken into three groups with each group receiving a different concentration of new genes.

FIX levels in the first subject have remained at 2 percent for nearly two years, while the two patients treated with the highest dose have seen FIX levels rise to between 3 and 12 percent, researchers said.

One high-dose subject developed elevated levels of transaminases, an indicator of possible liver damage, and another had a slight increase in liver enzymes. Both cases were resolved with steroids, the researchers said.

Plans are to treat more patients with the highest dose used so far, and if research continues to succeed, the treatment could be widely available “in the next five years or so,” said Dr. Amit Nathwani, co-lead study author of the Department of Hematology at UCL Cancer Institute in London.

He also said the team was working to use the technique for treating hemophilia A.

ISI Group analyst Mark Schoenebaum said the gene therapy could pose big competition for companies such as Biogen Idec that are producing recombinant factor concentrates.

“This clearly presents a curveball to our (and much of Wall Street’s) assumptions around the future of the hemophilia market,” he said in an email to investors.

The analyst said estimated sales of the hemophilia factors accounted for between $10 and $17 of his $125 price target for shares of Biogen, which closed at $112.95 on Friday.

People with hemophilia bleed more following trauma than people without the disease, and those with severe disease may bleed spontaneously.

Hemophilia B is much less common than hemophilia A. About one in five hemophilia patients has hemophilia B, according to the National Institutes of Health.

The global market for Factor VIII products is about $5 billion, while the market for Factor IX is worth about $1 billion.

Hemophilia is an inherited condition that affects men more frequently. Worldwide, about one in 5,000 men is born with hemophilia A and 1 in 25,000 men is born with hemophilia B each year.

(Reporting by Deena Beasley)

Tulane researcher finds treatment for hemophilia

DEERFIELD, ILL., November 2, 2011 – Results from an investigator-initiated study, which evaluated whether prophylactic use of FEIBA [Anti-inhibitor Coagulant Complex] can achieve a decrease in the frequency of joint and other bleeding events in patients with severe hemophilia A and inhibitors compared to on-demand therapy, were published today in The New England Journal of Medicine.  Patients with severe hemophilia A and inhibitors are at increased risk for serious bleeding complications.  Effective strategies to prevent bleeding in inhibitor patients have not yet been established.  Prophylaxis, where approved, is used to prevent a bleed and on-demand treatment is used only at the time of a bleeding episode.

“The single greatest remaining challenge in the management of hemophilia is the development of inhibitors, often occurring in young patients, that can lead to more difficult to control and sometimes life-threatening bleeding,” said Bruce Ewenstein, M.D., Ph.D., vice president, clinical affairs in Baxter’s BioScience business.  “The Pro-FEIBA investigator-initiated study is the first randomized prospective, controlled clinical trial to evaluate the ability of FEIBA prophylaxis to reduce bleeding events, which is particularly encouraging given that there are limited treatment options available for these patients.”

The Prophylaxis with Factor Eight Inhibitor Bypassing Activity (Pro-FEIBA) study reported that patients with severe hemophilia A treated with FEIBA prophylactically during a six-month period experienced a 62 percent reduction in all bleeds in the prophylaxis period, an average of 5 bleeding events compared to an average of 13.1 during the on-demand treatment period.  Sixty two percent of patients (16 of 26) were in the group that responded well to prophylaxis treatment, defined as those who had a greater than or equal to 50 percent reduction in overall bleeding, the target for success defined in the study protocol.  In this “good responder group,” the overall reduction in bleeding rate was 84 percent.  Thirty eight percent of patients (10 of 26) had a less than 50 percent reduction in bleeding events during the prophylactic period.  In this group, bleeding was reduced by 28 percent.  Two patients had an increase in bleeding events in the prophylaxis period.

Secondary outcome measurements were joint bleeding and target joint bleeding.  During the prophylaxis period, patients experienced a 61 percent reduction in joint bleeding, an average of 4.2 joint bleeds versus an average of 10.8 during the on-demand treatment period.  In target joints (those most prone to frequent bleeding, such as the elbow, knee and ankle), patients experienced a 72 percent reduction in bleeding.  The number of patients with bleeding in target joints decreased from 18 to 11. Of those patients in the study achieving a reduction in bleeds, all were achieved with three doses of FEIBA (85 U/kg ± 15 percent) per week.

One adverse event related to the study drug was an allergic reaction.  Three patients (9 percent) had multiple events related to central venous access devices, including infection, bleeding, and line placement and removal.

A limitation of the study was its relatively short duration.  While joint and other bleeding episodes were reduced during the six-month prophylaxis period, a longer, larger, parallel design trial is needed to determine if regular FEIBA infusions are a safe and effective treatment option for hemophilia A patients with inhibitors.  In addition, the authors state it is not possible to draw conclusions regarding relationships between patient age and the benefits of prophylaxis.  A Baxter-sponsored clinical study, FEIBA PROOF, is evaluating the efficacy and safety of FEIBA prophylaxis compared to on-demand treatment in those living with hemophilia with high-titer inhibitors. 

The Pro-FEIBA study was conducted by lead investigators Cindy Leissinger, M.D., from the Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center, New Orleans, USA, and Alessandro Gringeri, M.D., from the Department of Medicine and Medical Specialties, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy.  The lead investigators oversaw all aspects of the study including design, data collection and analysis and manuscript development and submission.  Baxter supplied the study drug (FEIBA) and provided a financial grant to support the study and authoring of the manuscript.  The manuscript was subsequently revised by the authors who assumed responsibility for its accuracy and completeness.

About the Study Design
The objective of the investigator-initiated Pro-FEIBA study was to test if prophylaxis with FEIBA over a six-month period may be safe and effective in preventing joint and other bleeds in severe hemophilia A patients with inhibitors compared to on-demand treatment.  Following the initial six-month study period (with 12 patients receiving on-demand therapy and 14 receiving prophylaxis), each group crossed-over to the alternate treatment period for six months after a three-month wash-out period.  The crossover design produced valid results with fewer patients than required for a parallel study design¹.  Thirty-four patients were enrolled in the study, with 26 patients evaluated in the final analysis.

About Hemophilia (A & B) and Inhibitors
Hemophilia is a rare genetic blood clotting disorder that primarily affects males. People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood.  In people with hemophilia A, clotting factor VIII is not present in sufficient amounts or is absent.  People with hemophilia do not bleed more profusely or faster than normal but bleed for a longer period of time. 

Hemophilia is usually inherited, and about one in every 5,000 males is born with the disorder.  About one third of new cases are caused by a new mutation of the gene in the mother or the child.  In these cases, there is no previous history of hemophilia in the family. According to the World Federation of Hemophilia, more than 400,000 people in the world have hemophilia.  All races and economic groups are affected equally.

Inhibitor development is considered one of the most serious adverse reactions associated with hemophilia treatment.  Studies suggest this may occur in three out of every 10 people with severe hemophilia A and one out of every 20 people with hemophilia B. Inhibitors are antibodies that people with hemophilia can generate following exposure to blood clotting factor replacement therapy.  These antibodies neutralize (inhibit) the action of clotting factor, which increases the risk of bleeding in people with inhibitors. Hemophilia patients with inhibitors have an increased risk of uncontrolled bleeding and bleeds are much more difficult to control compared to patients without inhibitors.  Consequently, these patients can develop complications such as increased need for surgery and increased complexity of surgery. 

The information in this statement is intended for scientific exchange only and is not intended for any other purpose.

About FEIBA
FEIBA is not indicated for prophylaxis use in the United States.  Canada, Italy, The Netherlands, Israel, Australia/New Zealand, Japan, South Korea, and Taiwan also do not have a prophylaxis indication.

Indications
In the US, FEIBA NF [Anti-Inhibitor Coagulant Complex] is indicated for the control of spontaneous bleeding episodes or to cover surgical interventions in hemophilia A and hemophilia B patients with inhibitors.

Clinical experience suggests that patients with a Factor VIII inhibitor titer of less than 5 B.U. may be successfully treated with Antihemophilic Factor.

Patients with titers ranging between 5 and 10 B.U. may either be treated with Antihemophilic Factor or FEIBA NF. Cases with Factor VIII inhibitor titers greater than 10 B.U. have generally been refractory to treatment with Antihemophilic Factor.

Detailed Risk Information About FEIBA NF
Thrombotic and thromboembolic events have been reported during postmarketing surveillance following infusion of FEIBA VH or FEIBA NF, particularly following the administration of high doses and/or in patients with thrombotic risk factors.

The use of FEIBA NF is contraindicated:

• In patients who have known anaphylactic or severe hypersensitivity reactions to the product
• In patients who are known to have a normal coagulation mechanism
• For the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX
• In patients with significant signs of disseminated intravascular coagulation (DIC)
• In patients with acute thrombosis or embolism (including myocardial infarction)

At first sign or symptoms of an infusion/hypersensitivity reaction or a thrombotic/thromboembolic event, FEIBA NF administration should be stopped immediately and diagnostic and therapeutic measures initiated as appropriate.

Allergic-type hypersensitivity reactions, including severe anaphylactoid reactions, have been reported following the infusion of FEIBA. The symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension; these reactions can be severe and can be systemic.

Many of the reported cases of thromboembolic events occurred with doses above 200 units/kg/day or in patients with other risk factors.

Infusion of FEIBA NF should not exceed single dosage of 100 U/kg and daily doses of 200 U/kg of body weight. Patients receiving more than 100 U/kg of FEIBA NF must be monitored for the development of DIC and/or symptoms of acute coronary ischemia. High doses of FEIBA NF should be given only as long as absolutely necessary to stop bleeding.

FEIBA VH or FEIBA NF should be used with particular caution and only if there are no therapeutic alternatives in patients at risk of DIC, arterial or venous thrombosis.

If clinical signs of intravascular coagulation occur, which include changes in blood pressure, changes in pulse rate, respiratory distress, chest pain and/or cough, infusion of FEIBA NF should be stopped promptly.

Non-hemophilic patients with acquired inhibitors against factors VIII, IX or XII may have both a bleeding tendency and an increased risk of thrombosis at the same time.

FEIBA NF is made from human plasma. It may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) prion.

Adverse reactions reported in clinical studies with FEIBA were anamnestic response, somnolence, dizziness, dysgeusia, dyspnea, hypoesthesia, nausea, chills, pyrexia, chest pain and chest discomfort.

For information on FEIBA use in the United States, please visit:
http://www.baxter.com/healthcare_professionals/products/feiba_nf.html

Licenses and licensing conditions may vary from country to country; therefore please always consult your local full prescribing information. Please check FEIBA website for information on indications approved in other countries.

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, 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.

Baxter and Feiba are registered trademarks of Baxter International Inc., its subsidiaries or affiliates.

1. Louis TA, Lavori PW, Bailar JC, 3rd, Polansky M. Crossover and self-controlled designs in clinical research. N Engl J Med 1984;310:24-31.

Originally from Baxter website.

 

Trends in bleeding patterns during prophylaxis for severe haemophilia: observations from a series of prospective clinical trials

From:  Haemophilia

K. FISCHER¹, P. COLLINS², S. BJÖRKMAN³, V. BLANCHETTE⁴, M. OH⁵, S. FRITSCH⁵, P. SCHROTH⁵, G. SPOTTS⁵, B. EWENSTEIN⁵

Article first published online: 7 FEB 2011

DOI: 10.1111/j.1365-2516.2010.02450.x

Summary.  Replacement therapy or prophylaxis, has become the standard of care for the treatment of severe haemophilia A. To describe bleeding patterns in children, adolescents and adults on prophylaxis and their observed relationships to times of infusion (during the week and during the day) as well as season of the year. Data from Advate pre-licensure prospective clinical trials from 145 patients with factor VIII (FVIII) <1%, were used. All patients underwent a 48-h pharmacokinetic study. The 10–65 year group had ≥75 exposure days on fixed prophylaxis (25–40 IU kg⁻¹ 3–4x per week). Prophylaxis was not fixed but similar for 1–6 year olds. Bleeding patterns were analysed. Overall, 700 bleeds were observed in 110/145 patients. All were treated with prophylaxis, mean dose 108 IU kg⁻¹ week⁻¹ in on average 2.9 infusions (1–6 years), 86 IU kg ⁻¹week⁻¹ in 2.7 infusions (10–17 years),and 75 IU kg ⁻¹week⁻¹ in 2.6 infusions (18–65 years), respectively. On prophylaxis, median total bleeds per year were low at 3.1 for patients aged 1–6 years, 3.3 for those aged 10–17 years and 2.1 for patients aged 18–65 years. Patients aged 1–6 years had predominantly soft tissue bleeds (79%). Incidence of joint bleeding was not associated with season, but was significantly lower in patients who infused FVIII in the mornings: median 0 per year (IQR 0.0–0.4) compared to those who infused later [median 1.8 per year (IQR 0.0–5.2)]. Older patients predominantly experienced joint bleeds (50% and 62%, respectively). More joint bleeds occurred during the summer [43 and 46% respectively, (P < 0.01)]. Bleeding patterns in patients on prophylaxis varied according to age. In addition, the 10–65 year olds showed increased bleeding during the summer. After confirmation in prospective studies, this information may be used to improve tailoring of prophylactic treatment.

A Randomized Clinical Trial of Prophylaxis in Children with Hemophilia A (the ESPRIT Study).

From: PubMed.gov

J Thromb Haemost. 2011 Jan 21. doi: 10.1111/j.1538-7836.2011.04214.x. [Epub ahead of print]

Gringeri A, Lundin B, Mackensen SV, Mantovani L, Mannucci PM; and the ESPRIT Study Group.

Department of Medicine and Medical Specialities, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico and University of Milan, Milan, Italy Department of Radiology, University Hospital of Lund, Lund, Sweden Institute of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany Centre of Pharmacoeconomics, University Federico II of Naples, Naples, Italy Scientific Direction, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.

Abstract

Background: Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients’ well-being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and well-being perception of children with hemophilia.

Objective: This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image-proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10-year time period.

Methods: Forty-five children with severe hemophilia A, aged 1-7 years (median 4), with negative clinical-radiological joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU/Kg 3x week) or episodic therapy with ≥25 IU/Kg every 12-24 hours until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated.

Results: Twenty-one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events/patient/month (p<0.02). Plain-film radiology showed signs of arthropathy in 6 patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (p<0.05). Prophylaxis was more effective when started early (≤36 months) with patients having less joint bleeds (0.12 joint bleeds/patient/month) and no radiologic signs of arthropathy.

Conclusion: This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.

© 2011 International Society on Thrombosis and Haemostasis

Hemophilia A Prophylaxis Best If Lifelong

By Nancy Walsh, Staff Writer, MedPage Today
Published: November 15, 2010
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

NEW ORLEANS — Adults with severe hemophilia A who received lifelong prophylactic clotting factor VIII replacement therapy had notably better health-related quality of life than those who had limited treatment, researchers reported here.Among patients who had had continuous prophylaxis, physical functioning scores were approximately 57 on the short-form SF-12 scale, compared with scores of 38 for those who had never been given prophylactic treatment (P<0.001), Xiaolan Ye, MD, of Baxter Bioscience in Deerfield, Ill., and colleagues reported in a poster session at the annual meeting of the National Hemophilia Foundation. Patients with hemophilia A lack coagulation factor VIII and are prone to severe bleeds that can be crippling or life-threatening. The condition is found in about one out of every 5,000 male live births. Treatment involves the administration of replacement clotting factor, either regularly — several times a week — or when bleeding occurs. Despite previous research demonstrating better outcomes such as less joint damage related to bleeding with prophylactic treatment, obstacles remain. One barrier is the cost, which for a child has been estimated to reach $300,000 annually, as well as problems with venous access and unwillingness on the part of patients to undergo frequent infusions. To explore the effects of prophylactic versus on-demand treatment on patients’ quality of life, Ye and colleagues surveyed 117 patients whose mean age was 25.5 years. A total of 53 patients were children whose mean age was 10.5 years, while 64 were adults whose mean age was 37.9 years. Among the pediatric patients, 96% were currently receiving prophylaxis, although 76% of these had initially started treatment on demand, switching to prophylaxis at about age 4 years. Among the children who had always been on prophylaxis, treatment usually started during the first year of life. No statistically significant differences were seen on any domain of the Pediatric Quality of Life Inventory, which measures physical, emotional, social, and school functioning, between children who were always on prophylaxis and those who switched to prophylaxis from on-demand treatment. This finding, according to the researchers, was “possibly due to on-demand patients switching to prophylaxis on average by age 4.” By adulthood, however, differences in health-related quality of life had emerged, with the highest scores being seen in the six patients who had always been on prophylaxis. Half of the adults had never had prophylaxis, while 20 had switched from on-demand to prophylaxis at an average age of 17, remaining on regular prophylaxis thereafter. An additional six adults had switched to prophylaxis at an average age of 13, but returned to on-demand treatment at about age 22. Physical functioning scores for adults who previously received on-demand therapy but switched to prophylaxis fell between the always-prophylaxis and never-prophylaxis groups, at 41. Statistically higher scores in physical functioning with prophylaxis were accompanied by significantly better scores on the physical component domain of the SF-12, Ye and colleagues reported. On this domain, patients always on prophylaxis had mean scores of 51, while those who switched to prophylaxis scored 40 and those who never had prophylaxis had scores averaging 37 (P<0.05), the researchers found. On all other domains, including bodily pain, general health, social functioning, and mental health, the lifelong prophylaxis group scored highest, although the differences were not statistically significant. The investigators concluded that different treatment patterns were seen for children and adults with hemophilia A, with only half of the adults ever having received prophylaxis despite the finding that physical functioning was improved with regular treatment. All authors were employees of Baxter Bioscience.

Primary source: National Hemophilia Foundation Source reference: Ye X, et al “Treatment patterns and quality of life among hemophilia A patients in the United States” NHF 2010; Abstract SPI2.

Prophylaxis Vs. Timely On-Demand Therapy: Joint Bleeds

Prophylaxis More Effective at Preventing Joint Bleeds Than Timely, On-Demand Therapy: Presented at Hemophilia 2010

By Thomas R. Collins
Taken from: DOC Guide

BUENOS AIRES — July 13, 2010 — Prophylaxis treatment resulted in half as many bleeding events in children aged younger than 7 years with haemophilia A, compared with those getting timely, on-demand treatment, according to the latest results from a 10-year study out of Italy presented July 12 at the Hemophilia 2010 World Congress.

Prophylaxis also resulted in half as much joint damage, reported Alessandro Gringeri, MD, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy.

In the Evaluation Study on Prophylaxis: A Randomized Italian Trial (ESPRIT) study, 23 children with haemophilia A were randomised to the prophylaxis group and 22 to the on-demand treatment group. Two patients in the prophylaxis group dropped out after randomisation, as did 3 in the on-demand group.

The young patients averaged 49.7 months in the prophylaxis group and 48.8 months in the episodic treatment group.

The on-demand group was treated with a recombinant FVIII concentrate of at least 25 IU/kg within 6 hours from a bleeding occurrence. The prophylaxis group was treated with 25 IU/kg 3 times a week on nonconsecutive days, but dosage could be adjusted if needed.

Breakthrough bleeds were treated like those in the on-demand group.

Patients were followed for an average of 74 months.

Ultimately, in the prophylaxis group, the starting dose was able to maintain FVIII trough levels >1% in only a third of the patients, so the dose had to be increased.

The total average number of bleeding events per patient in the prophylaxis group was 38, averaging .52 events per patient per month. There was an average of 82 bleeding events per patient in the other group, averaging 1 event per patient per month (P < .01).

There were 15 instances of joint bleeds per patient, averaging .2 per patient per month in the prophylaxis group. There were 40 per patient in the on-demand group, for an average of .53 per patient per month (P < .01).

According to radiographic findings, 6 patients suffered joint damage in the prophylaxis group, compared with 14 in the on-demand treatment group (P < .05).

Of the 10 patients in the prophylaxis group who needed port-a-caths, 6 developed infections.

“Use of CVC [central venous catheters] is complicated by a higher risk of infection,” Dr. Gringeri said in his presentation.

Seven of the children in the prophylaxis group had no joint bleeds at all, compared with 2 in the on-demand group.

Five of the 40 patients developed an inhibitor — 3 of the 21 in the prophylaxis group and 2 of the 19 in the on-demand group.

“Prophylaxis can reduce joint damage at the average dose of 30 IU/kg 3 times a week,” Dr. Gringeri said. “Prophylaxis might prevent joint damage also in those patients who start prophylaxis later, but with a lower rate of efficacy.”

Funding for this study was provided by Baxter International Inc.

[Presentation title: A Randomized Clinical Trial on Prophylaxis vs Episodic Treatment in Children With Haemophilia A: The ESPRIT Study. Abstract 07FP06]

Hemophilia Care – Past, Present, and Future

Haemophilia care then, now and in the future

This is a link to an article from “Haemophilia: the Official Journal of the World Federation of Hemophilia” about the past, current, and future pediatric care of Hemophilia patients, as well as current and future geriatric care for Hemophilia patients.  Volume 15, Issue s1, 2009.Pages: 2–7

The article recently became viewable online without a fee.  I hope you find the information relevant.  Life Expectancy data, long-acting FVIII products, and demographic data was included in the report.