Renowned hematologist Dr. Edward Shanbrom dies

The Associated Press

Posted:   03/04/2012

TUSTIN, Calif.—Dr. Edward Shanbrom, a pioneering hematologist who invented a widely used process for removing viruses from blood plasma and helped develop a breakthrough treatment for hemophilia, has died in Southern California.

Shanbrom died of natural causes Feb. 20 at his home in Tustin, according to a statement from his family. He was 87.

While on the executive staff at Baxter Laboratories in the 1960s the Connecticut native helped come up with a method, still in use today, to produce large quantities of a blood clotting factor that is absent in hemophiliacs. This breakthrough therapy made it possible for those suffering from hemophilia to lead more normal lives.

“Hemophilia patients and blood product recipients worldwide have benefited from Dr. Shanbrom’s work,” Samuel D. Anderson, his colleague and a former biotechnology executive, said in a statement to the Los Angeles Times.

In the 1980s, while conducting research at his home, Shanbrom developed a blood purification technique that uses mild detergents to scrub viruses, bacteria and other contaminants out of plasma.

Shanbrom held 49 U.S. patents and 91 international patents in areas ranging from nutraceuticals to antiseptics to blood products, his family said. In 1988 the New York Blood Center bought his patented processes for scrubbing viruses from transfusion blood.

He practiced hematology and oncology at the City of Hope Medical Center in Duarte, Orange County General Hospital and St. Joseph Hospital in Orange.

Shanbrom was also a clinical instructor at the University of California, Los Angeles and at UC Irvine. In 2007 the Edward Shanbrom, M.D. Hall was dedicated on the UC Irvine campus in recognition of his pioneering hematology research and support of the university. The building is also home to the Edward Shanbrom, M.D. Laboratory for the Study of Blood and Natural Products.

For more inforamation on Edward Shanbrom , M.D. click here.

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.

 

First Clinical Study Comparing Pharmacokinetic Profiles of VWF/FVIII Products Published in Medical Journal

By PR Newswire: Biotechnology
Monday, 07 November 2011 09:00

The study compared the PK profiles of wilate® (Von Willebrand Factor/Factor VIII Concentrate, Human) and Humate-P® Human Plasma-derived Von Willebrand Factor (HP-VWF/FVIII) Concentrate.

As the most common inherited bleeding disorder in humans, VWD affects one to two percent of the general population or approximately 3 million people in the United States. Originally approved in Germany in 2005, wilate® is available in 46 countries worldwide. In December 2009, the U.S. Food and Drug Administration (FDA) granted Octapharma orphan drug exclusivity for wilate® for treating certain types of VWD.

The study entitled, “The pharmacokinetic diversity of two Von Willebrand Factor (VWF)/Factor VIII (FVIII) concentrates in subjects with congenital Von Willebrand Disease,” is available online through National Center for Biotechnology Information. PK profiles of VWF/FVIII “concentrates can be important for evaluation of treatment efficacy and safety” in VWD patients, the journal article reported.

“This PK comparison of wilate® and Humate-P® showed that the pharmacokinetic parameters of VWF component in these two concentrates are similar, while the pharmacokinetic profile of the FVIII:C components were significantly different. wilate® exhibited an exponential decay curve for FVIII:C within the first 12-24 hours post injection whereas Humate-P® FVIII:C PK showed a plateau in the same time period. Both products showed similar multimer profiles and a multimeric decay pattern that paralleled that of the VWF:RCo concentration curves over time, with a minimal reduction in multimers of high molecular weight relative to control plasma. The authors concluded that an approximate a 1:1 ratio of VWF:RCo to FVIII:C and the parallel PK profile of both coagulation factors may simplify dosing and monitoring of VWD product and may help avoid the clinical complications of over- or under-dosing of these key coagulation parameters in clinical scenarios requiring multiple dosing.”

The study’s investigators were: Craig M. Kessler, M.D. (Hemophilia and Thrombophilia Comprehensive Treatment Center, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, D.C.); Jerry S. Powell, M.D. (Hemophilia Treatment Center, University of California, Davis, Sacramento, Calif.); Jorge DiPaola, M.D. (Mountain State Regional Hemophilia and Thrombosis Center, University of Colorado at Denver and Health Sciences Center, Aurora, Colo.); Ken D. Friedman, M.D. (Comprehensive Center for Bleeding Disorders, Children’s Hospital of Wisconsin, Milwaukee, Wis.); Joan Cox Gill, M.D. (Comprehensive Center for Bleeding Disorders, Children’s Hospital of Wisconsin, Milwaukee, Wis.); Arthur R. Thompson, M.D., Ph.D. (Hemophilia Care and Coagulation Labs, University of Washington, Seattle, Wash.); and Christopher E. Walsh, M.D., Ph.D. (Comprehensive Hemophilia Center, Mount Sinai School of Medicine, New York).

wilate® is a plasma-derived, stable, highly purified concentrate of freeze-dried human Von Willebrand Factor (VWF) and coagulation factor VIII (FVIII). Two well-established virus inactivation steps are incorporated into the manufacturing process of wilate®, specifically a solvent/detergent (S/D) and terminal dry heat treatment.

About theOctapharma Group

Headquartered in Lachen, Switzerland, Octapharma AG is one of the largest human protein products manufacturers in the world and has been committed to patient care and medical innovation for over 28 years. Octapharma’s core business is the development, production and sale of high quality human protein therapies from both human plasma and human cell-lines, including immune globulin intravenous (IGIV). In the U.S., Octapharma’s IGIV product, octagam® (immune globulin intravenous [human] 5%), is used to treat primary immune deficiencies, and Octapharma’s Albumin (human)® is indicated for the restoration and maintenance of circulating blood volume. Octapharma’s wilate® (Von Willebrand Factor/Coagulation Factor VIII Concentrate) received orphan drug exclusivity from the U.S. Food and Drug Administration (FDA) for the treatment of certain types ofVon Willebrand Disease (VWD). Octapharma employs over 4,000 people and has biopharmaceutical experience in 80 countries worldwide, including the United States, where Octapharma USA is located in Hoboken, N.J.  Octapharma operates two state-of-the-art production sites licensed by the FDA, providing a high level of production flexibility. For more information, please visit www.octapharma.com or www.wilateusa.com.

Forward-looking statements

This news release contains forward-looking statements, which include known and unknown risks, uncertainties and other factors not under the company’s control. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. These factors include results of current or pending research and development activities and actions by the FDA or other regulatory authorities.

SOURCE Octapharma USA

RELATED LINKS
http://www.octapharma.com

Conflicts in medical management of hemophilia

entire Article can be found here: Conflicts in medical management of hemophilia.

 By Everett Winslow Lovrien, M. D  (Author of “Doctor Guilt?“)
WordPress blog

Hemophilia is a medical disorder that is part of our genetic load as humans. It will never disappear. Therefore, the only way to live with it is to receive adequate medical management. Its effects on those males who have inherited the disorder that affects their blood clotting without treatment includes recurrent hemorrhages (bleeds) into joints as well as internal bleeding. The bleeds are painful, resulting in disuse, disability and crippling. The first signs usually appear in early childhood. A child who suffers a mouth bleed can slowly lose enough blood to result in death.

Prior to 1960, the expected life of a child born with severe hemophilia in the USA was less than 11 years. A common cause of death in childhood was bleeding into the brain, an intracerebral hemorrhage. This agonizing threat could be overcome with the discovery of Cryoprecipitate in 1964 by Dr. Judith Pool at Stanford University. The missing precursor to deficient clotting factor, antihemophilia factor VIII (AHF VIII) was obtained from the blood plasma of normal donors. A further step led to the production of AHF in the form of a lyophilized powder (Concentrates) that could be re-constituted and infused at home to treat bleeding. The introduction of concentrates was a marvelous innovative form of treatment that considerably improved the lives of those born with hemophilia by eliminating agonizing suffering.

Constraint in hemophilia treatment by HIV and hepatitis viruses

Despite the great success of Concentrate therapy for replacement of missing AHF in persons who have hemophilia, two conflicts have clouded the brightness of its use. The first major hazard of replacement therapy was the discovery that the magic medicine was contaminated with hepatitis viruses and HIV, the virus that cause AIDS. The drug companies that manufactured AHF Concentrates derived from plasma sacrificed safety bypassing purification in their drive for profitability. Thousands of boys and men who had hemophilia died all over the world from liver failure and AIDS as a result of the polluted medicine they infused to treat their bleeding episodes. More than 10,000 persons with hemophilia became HIV infected in the USA, which could have been prevented.

High costs limit availability of hemophilia treatment

The second conflict in AHF replacement is the cost of the medicine. AHF infusions to treat or prevent bleeds in hemophilia are not infused just once; instead infusions are required every few days in childhood. A person with severe hemophilia often exceeds 1,000 infusions by adulthood. The cost of treatment depends on the amount of AHF infused. A child requires less than an adult. A single treatment costs $1,000 to $2,000 for an adult. In the USA, estimates reveal that 12,000 persons with severe Type A hemophilia infuse an average of 171,760 units of AHF each year totaling 2,060,000,000 AHF units, including surgery. The average maintenance per person without surgery is less. However, recent recommendations for the prevention of bleeding in hemophilia include scheduled prophylactic infusions of Factor VIII, three times each week. A person who receives 150 infusions each year at 750 units per infusion will receive 112,500 AHF units; if the amount is 1,000 units three times each week, the yearly infusions total 150,000 units. The pharmaceutical manufacturing of AHF concentrates, as plasma derivatives and by genetic recombinant methods, world-wide is a multi-billion dollar industry. Production of AHF in 1995 equaled $2.4 billion, and amounted to $6 billion by 2011. AHF concentrates are sold primarily in countries with high incomes (RE: J.S. Stonebraker et al, Hemophilia (2010), 16, 33-46).

Hemophilia appears in males from all of the world’s races. With a world population of 7,000,000,000 (CIA, 2010) and an average birth rate of 20 per thousand individuals, there are 140,000,000 births each year in the world. One half are males, (70,000,000). One in 5,000 newborn males has hemophilia, equaling 14,000 new cases of hemophilia that are born in the world each year.

Within the U.S., with a population of 310,000,000, a birth rate of 14 per thousand equates to 4,340,000 births each year. In the U.S. 2,170,000 males are born annually. Experience has revealed that one in 5,000 will have hemophilia, equaling 434 new cases of hemophilia in the USA each year. Approximately 20,000 persons living in the USA have hemophilia ( RE: J.S. Stonebraker et al Hemophilia (2010), 16, 20-32). Of these, 12,000 are males who have severe type A hemophilia requiring Factor VIII replacement infusions.

Thanks to the federal government’s establishment of Hemophilia Treatment Centers, whose goal is to identify all of the persons who have hemophilia within the center’s health region, most cases of hemophilia in the USA, as well as in other high income countries are identified. Recognition is a necessary step that leads to treatment and relief from suffering.

But, that’s not the case in the major parts of the world. It is estimated that one–half, or even three-fourths of the children born in the world who suffer from hemophilia receive inadequate or no treatment (World Federation of Hemophilia, WFH). Often, they are not identified. The lack of treatment in economically poor counties of the world is the result of the high cost of the replacement AHF medicine, made in America without cost controls, that is not affordable in many countries.

Information provided by Mr. Patrick Robert of Marketing Research Bureau, Orange, Connecticut, for 2009 revealed the following:

Factor VIII sales in the USA (2009)
Plasma derived AHF Factor VIII	360,000,000 units
Recombinant AHF Factor VIII	1,700,000,000 units
	Total 2,060,000,000 units

 

Factor VIII worldwide sales (2008)
Plasma derived AHF Factor VIII	2,900,000,000 units
Recombinant AHF Factor VIII	4,000,000,000 units
	Total 6,900,000,000 units

 

Price of Factor VIII
Recombinant Factor VIII	$.90 -$.99 / unit
Plasma derived AHF Factor VIII	$.60/ unit within the USA
	$.50/ unit outside the USA

The USA includes only 4.7% of the world’s population but it uses 30% of the Factor VIII concentrates produced in the world. 12,000 males (Type A hemophilia) using 2.06 billion units of AHF annually average 171,670 units for each person. This amount of AHF appears to be excessive but considering the large amounts of AHF utilized during surgery, prophylactic infusion therapy three times each week, and induction of immune tolerance to overcome inhibitors the amount may be even higher. Mr. Mark Skinner, president of WFH, believes the utilization of AHF will increase as children in the USA, who have been maintained on prophylaxis become adults. An adult male weighing 175 lbs who infuses 2,000 units of Factor VIII prophylactically three times each week uses 312,000 units each year, at a cost of $187,200 to $308,880 depending on whether recombinant or plasma-derived Factor VIII is infused.

Donations of AHF from pharmaceutical manufacturers to underserved person have been welcome. Pfizer has provided 10 million units of its ReFacto AHF to persons suffering from hemophilia in underserved countries, valued at $13 million (Medical.net/news 2010-02-03). Medical insurance providers may question the high prices of AHF Factor VIII they pay to pharmaceutical manufacturers for the benefits of their subscribers while they give away medicine to others without a cost. There remains a dilemma – a marvelous treatment exists but it is not affordable for most persons in the world. AHF treatment is available for persons who live in rich countries—so, a societal issue arises. If medicine exists to provide treatment, relieve pain and suffering, prevent disability and prolong life expectancy, is it a basic human right that the medicine should be available to everyone who needs it?

WFH and the National Hemophilia Foundation (NHF) continue their advocacy for all persons born with hemophilia. The Hemophilia Treatment Centers (HTC) in the USA have improved the management of hemophilia resulting in an improved quality of life and increased life expectancy within the USA. Other countries that have a high average income have also experienced the improvement of hemophilia care as the result of the pharmaceutical manufacturers’ entrepreneurship. The innovative production of AHF for the treatment of hemophilia as a safe plasma derivative and by genetic recombinant methods by industry has been remarkable. The challenge ahead for treating hemophilia has shifted from production of medicine to distribution.

FDA approved Corifact to treat congenital Factor XIII

FDA approves product to prevent bleeding in people with rare genetic defect
Corifact is 1st treatment for congenital Factor XIII Deficiency

FDA NEWS RELEASE
For Immediate Release: Feb. 17, 2011
The U.S. Food and Drug Administration today approved Corifact, the first product intended to prevent bleeding in people with the rare genetic defect congenital Factor XIII deficiency.

Patients with congenital Factor XIII deficiency don’t make enough Factor XIII, a substance that circulates in the blood and is important for normal clotting. Without treatment, people with the condition are at risk for life-threatening bleeding.

Congenital Factor XIII deficiency is rare and affects 1 out of every 3 million to 5 million people in the United States. The deficiency may lead to soft tissue bruising, mucosal bleeding and fatal intracranial bleeding. Newborns with Factor XIII deficiency may have umbilical cord bleeding.

“This product helps fill an important need,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research.

Corifact received orphan-drug designation by the FDA because it is intended for use in a rare disease or condition. It was approved for marketing under the FDA’s accelerated approval regulations that require an on-going study to demonstrate that patients actually receive the clinical benefit predicted by the data obtained so far.

The FDA approved Corifact based on results of a clinical study of 14 people, including children, with congenital Factor XIII deficiency. The most common side effects observed were hypersensitivity reactions (allergy, rash, pruritus, and erythema), chills, fever, arthralgia, headache, elevated thrombin-antithrombin levels, and an increase in liver (hepatic) enzymes.

Corifact is made from the pooled plasma of healthy donors. People receiving Corifact may develop antibodies against Factor XIII that may make the product ineffective. It potentially can cause adverse events from abnormal clotting if doses higher than the labeled dose are given to patients.

Corifact is manufactured by CSL Behring of Marburg, Germany.

For more information: visit CSL Behring’s website.

For more information, including full prescribing information, visit http://www.corifact.com/.

Book – “Survivor: One Man’s Battle with HIV, Hemophilia, and Hepatitis c”

The life of someone fighting a serious disease is never easy. Vaughn Ripley is no different. He made a choice on how to deal with it and his book tells of his struggles and victories.

Movie – BAD BLOOD

Blood, Sweat and Tears

by Shawn Decker From POZ.com

POZ speaks with Marilyn Ness, Emmy Award-winning producer, about Bad Blood, a documentary that chronicles how the hemophilia community fought to protect the blood supply from HIV.

What inspired you to make a documentary about this often forgotten chapter in HIV/AIDS history?
I grew up with Mathew Kleiner [an HIV-positive advocate who died in 2003 of Hepatitis and complications due to HIV] in Brooklyn. I knew he had hemophilia, but other than [when we discussed] how rough we could get on the monkey bars, it didn’t really come up much. 

Coincidentally, my sister wound up in college with him at Cornell University [in New York state]. They became friends, so we all reconnected. In his junior year at Cornell, he decided to come out publicly [about the fact] that he had HIV and told his story of contracting HIV from Factor VIII, a blood-based medication that had been approved by the Food and Drug Administration (FDA).

Is that when you first learned that many people with hemophilia had contracted HIV through blood products?
I knew AIDS affected the “four Hs”: homosexuals, Haitians, hemophiliacs and heroin addicts. Like most people, I never stopped to consider how hemophiliacs got it. I knew it had something to do with blood, but I guess I thought they got it from a blood transfusion.

What startled me is that many hemophiliacs got it from Factor VIII. In order to make Factor VIII, blood went through rounds and rounds of treatment and processing that ultimately turned it into white powder. In the process, HIV-tainted blood was used. There was opportunity at each stage of production to address the viral contamination. But no one did, because no one knew what had happened.

Before HIV/AIDS, the hemophilia community went through a similar situation in which people were exposed accidentally to hepatitis B. Were the lax response to that incident and the resulting infections warning signs of things to come?
Yes, neither the pharmaceutical companies nor the FDA nor the doctors nor the patient advocacy groups insisted the product be cleaned of viruses. It’s actually such an unbelievable notion in many ways. [And they certainly didn’t advertise what happened.] I’m not surprised people don’t understand how hemophiliacs contracted HIV.

What do you hope people will take away from watching Bad Blood?
Once the hemophilia community began to [contract HIV], experts at the Centers for Disease Control and Prevention [CDC] realized pretty quickly it meant the virus was in the blood supply.

Had the CDC warnings been heeded, then steps could have—and should have—been taken to change the blood collection process in the United States. It is widely accepted that, had those changes been made, a good number of the 12,000 people who contracted HIV through blood transfusions [in addition to the 10,000 hemophiliacs] during that era might have been saved.

My hope is that this film, by raising awareness of what happened, will help keep the blood supply safe.

One of my favorite parts of the film shows how the hemophilia community became politically active regarding blood safety. It’s similar to how the gay community were leaders in advocating for condom use.  Blood safety gained national attention again in 2010 over discussions regarding the ban on blood donations by homosexuals. It was issued more than 20 years ago as an initial response to the AIDS crisis. But arguably it may be time to remove it. Do you believe the ban should be lifted?
In 1980, the gay community donated 5 percent of the nation’s blood. It was a true act of altruism and civic responsibility, considering less than 5 percent of all eligible donors donate today. So I understand fully the frustration of the gay community in being prohibited from donating blood in the United States.

On the flip side, I know the hemophilia community well and know they will bear 100 percent of the risk if another infectious agent makes its way into the U.S. blood supply.

I am hugely gratified that Gay Men’s Health Crisis [GMHC] saw Bad Blood and reached out to the bleeding groups to work together on coming up with a thoughtful process to reconsider the gay donor blood ban.

GMHC wants to use Bad Blood to educate its community on why patience is needed as scientists, public health officials and advocates like GMHC and the bleeding groups work together to make safe and fair blood donor policies in the United States.

Both the hemophilia and gay communities have lost so many people to this epidemic, it’s understandable that passions run so deep on both sides regarding gay donors.
In every way, what happened in the hemophilia community was an early warning sign about the safety of the U.S. blood supply.

And though many people with hemophilia no longer use blood-based therapies [they use genetically engineered products], that community still considers itself the guardians of the nation’s blood supply, [hoping to ensure] a tragedy like the one chronicled in Bad Blood will never again happen on their watch.

Personally, I feel we owe them a debt of gratitude for that.

Go to badblooddocumentary.com for more information.

Octapharma Clinical Trial Begins in the US and Germany Treating Hemophilia A Patients with First Recombinant Factor VIII Derived from a Human Cell-Line

LACHEN, Switzerland, Thursday, October 28th 2010 [ME NewsWire]:

(BUSINESS WIRE)– Octapharma, one of the largest human protein products manufacturers in the world, today announced that patients diagnosed with severe hemophilia A have started treatment with the first recombinant Factor VIII derived from a human cell line (Human-cl rhFVIII). Researchers are investigating pharmacokinetics, efficacy, safety and immunogenicity of Human-cl rhFVIII for previously treated patients with severe hemophilia A.

The prospective, randomized, actively controlled, open label, multicenter Phase 2 trial is being conducted at research centers in the US and Germany under the title “Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety and Immunogenicity of Human-cl rhFVIII, a Newly Developed Human Cell-Line Derived Recombinant FVIII Concentrate in Previously Treated Patients with Severe Hemophilia A.” The study started in spring 2010 and patient enrollment is well underway. Please visit www.clinicaltrials.gov for details.

Human-cl rhFVIII is a fourth-generation recombinant factor VIII (rFVIII) concentrate developed by Octapharma for the control and prevention of bleeding episodes and for surgical prophylaxis in patients with hemophilia A. Human-cl rhFVIII is produced in genetically modified Human Embryonic Kidney (HEK) 293F cells. Human-cl rhFVIII is currently the only rFVIII, which has a human glycosylation pattern. Today, the development of antibodies against infused FVIII represents the most devastating complication in modern Hemophilia A replacement therapy. The human glycosylation pattern in Human-cl rhFVIII should make it possible to avoid potentially immunogenic epitopes as expressed by hamster cells. This may result in improved safety and long-term reduced immunogenicity of Human-cl rhFVIII. During a previous first single-center clinical study, Human-cl rhFVIII demonstrated its safety and efficacy in 22 PTPs without causing any inhibitors or non-inhibitory antibodies against Human-cl rhFVIII.

Human-cl rhFVIII is concentrated and purified for virus inactivation/removal by solvent detergent and nanofiltration although the cell bank and end of production cells have been extensively tested to ensure they are free of any endogenous or infectious viruses. The process ensures that any theoretical virus contamination is safely inactivated and/or removed. The manufacturing of Human-cl rhFVIII is completely free of animal or human derived added materials. The clinical development plan for Human-cl rhFVIII follows the requirements of the U.S. Food and Drug Administration and European guidelines.

About the Octapharma Group

Headquartered in Lachen, Switzerland, Octapharma is one of the largest plasma products manufacturers in the world and has been committed to patient care and medical innovation for over 27 years. Octapharma’s core business is the development, production and sale of high quality human protein therapies from both human plasma and human cell lines. Octapharma is currently developing the first commercial recombinant coagulation FVIII from a human cell line (Human-cl rhFVIII), which is designed to reduce the overall immunogenic challenge (and resulting inhibitor formation) to the haemophilia A patient.

At the present time, Octapharma has 37 subsidiaries and representative offices. The company employs over 4,000 people and is making sales in 80 countries worldwide. For more information, please visit www.octapharma.com.

© Octapharma AG, 2010

For media enquiries, please contact:

Octapharma AG
Corporate Communications
Corinne Landolt
Tel.: +41 (55) 451 21 36
Corinne.Landolt@octapharma.com

Book Review: Dying in Vein

Name:  Dying in Vein: Blood, Deception … Justice

Description:

Photographer Kathy Seward MacKay and writer Stacy Milbouer bring to light one of the worst preventable medical disasters in United States history – the spread of the AIDS and hepatitis
viruses through the nation’s blood supply and its devastating effects on the world’s population of hemophiliacs and their families. Approximately 100,000 hemophiliacs were infected with the viruses.

The documentation of this tragedy is provided in a 1995 independent study by the Institute of Medicine – part of the National Academy of Sciences. In the report, medical experts estimated that up to 70 percent of the HIV infections in hemophiliacs may have been prevented had the FDA and the pharmaceutical companies acted when the warnings signs were evident in the early 1980s.

A timeline in “Dying in Vein” gives an overview of the blood supply problems, beginning with the first known outbreak of hepatitis in the 1940s. It is easy to see that decades later the deaths of thousands of people with bleeding disorders were largely a result of corporate greed by four pharmaceutical companies and FDA regulatory failure.

Mission Statement:

After the death of my 33-year-old husband, a hemophiliac infected by tainted blood products, I wanted to use my skills as a photographer to show the pain and suffering of the victims and the families of the blood-supply crisis within the hemophilia community. I wanted to tell the story with candid, real-life moments. It was also important for me to capture the fervent activism in this community, the everyday life of infected hemophiliacs and the strength of the human spirit. I wanted the people responsible for this travesty to see the toll their actions and decisions had on the lives of their victims. And I wanted to inspire those who saw these photographs to think, feel, maybe even act in response to it.

For my husband, David, living with the cloud of HIV over his head, was not an easy task, yet he lived a full life. As a special education teacher, he touched many lives and sent his students on the path to productivity, rather than ruin. The ripple effects of his contributions are still seen today. Yet, he died too young and his two sons have suffered from the absence of a father since the ages of 4 and 8.

While David was alive, he often suggested that I document the plight of an HIV-positive hemophiliac. He knew there was a whole generation of people with bleeding disorders who faced extinction. For me however, this was a topic I just did not want to cover – it was too close to home. I didn’t want to draw attention to the issue. I wanted to try to live a “normal” life. We believed he would remain one of the long-term survivors of HIV. Then, after he very suddenly died of liver failure from hepatitis C in 1997, I was thrown into the world of hemophilia, injustice and activism. I quickly learned that this horrific tragedy could have been prevented if it weren’t for corporate greed and the immoral decisions within our federal Public Health Service.

As a photographer, I could no longer ignore such an important story. I felt obligated to do my part for the cause. My main goal was to educate the public and to do my small part in preventing another tragedy of this nature. I soon realized how important it was to provide a voice to those who felt the government and the press ignored their stories.

“Dying in Vein” is for those victims of the blood supply crisis: Those who have perished. Those who are suffering. And those who have survived the death of their loved ones.

Dying in Vein is also for all healthcare consumers: Those who rely on drug companies to make the right decisions for us. Those who rely on the FDA to make the right decisions for us. And those who rely on doctors to make the right decisions for us.

Link to FaceBook page, here.

New Book – Hemophila History

Doctor Guilt?
by Everett Winslow Lovrien

Editorial Reviews

Product Description

Brent admired the chimpanzee he sketched at the zoo. He regarded the animal as contemplative. He was unaware that similar animals in the wilds of Africa were the source of a virus that would lead to his death from AIDS. Brent became infected with HIV from the medicine he infused to treat his hemophilia. At six months of age, his parents were alarmed when they discovered bruises on his chest which led to the discovery of hemophilia. From that moment forward, he received frequent intravenous infusions of concentrate to treat recurrent bleeding episodes. Infusions of the medicine relieved pain and suffering from bleeding. His life seemed normal. Unexpectedly, Brent’s life changed after the discovery of HIV contamination of the medicine. The medicine was manufactured from the plasma of paid blood donors. Unbeknownst to Brent, the plasma was polluted with HIV. The SIV in chimpanzees changed to become HIV in humans. But the chimpanzees were not the cause of the transfer of SIV in animals to HIV in humans. The change from SIV in animals to HIV in humans was the result of human activity. The change came about with the production of the hepatitis B vaccine. Who was responsible for the pollution of the hemophilia medicine with HIV and hepatitis viruses? Was Brent’s death preventable?

Product Details

• Hardcover: 500 pages
• Publisher: iUniverse.com (August 23, 2010)
• Language: English
• ISBN-10: 1450216846
• ISBN-13: 978-1450216845

Excerpt from the book….

This is the story of a boy who had hemophilia, a bleeding disorder that resulted in pain, disability and death before adulthood. A new medicine was developed which brought an end to suffering and increased longevity in persons with hemophilia.  The effect of the new medicine was like magic. It was a remarkable revolutionary advancement in the treatment of hemophilia, a medical disorder that had caused suffering for many previous centuries.

The medicine was manufactured from the plasma of paid blood donors.  Unexpectedly, a dark cloud descended when persons infusing the medicine became ill. It was discovered that the new medicine was polluted with hepatitis viruses and HIV.  By the time of discovery it was too late to prevent infection. The boy and 10,000 others in the USA became infected with HIV the virus that causes AIDS. He died from AIDS at age seventeen rather than have a prolonged life that was intended with the new medicine.  The medicine was sold to other countries resulting in thousands of deaths from AIDS all over the world.

In addition to the boy, others like him that received medical care at the same clinic he attended also became infected with HIV and hepatitis viruses. One hundred persons at the treatment center where he received his care died from AIDS or liver failure. A dozen other families who lost a son or father or husband were contacted or interviewed in their homes and asked if they blamed the doctors who prescribed the medicine that resulted in death. Doctors are supposed to provide treatment without causing harm to their patients. The doctors didn’t know that HIV, a new virus that causes AIDS, existed. But could they have known or should they have known?  Do the families view the doctors as guilty of causing harm and death?

The families believe the doctors were incorrect when they told the families to take the medicine and their loved one would live to become an old man and have a near normal life. But they do not believe the doctors are guilty.  They were using the best knowledge available at the time.

However, the families do believe the pharmaceutical manufacturers of the medicine are accountable for the deaths from AIDS in persons who infused their medicine to treat hemophilia. If there was suspicion that the medicine was polluted, why didn’t the producers of the medicine purify it by removing the viruses from the donor plasma?  The manufacturers replied that they didn’t know how to purify the medicine or that the methods of viral depletion were too expensive. But since then, reviews have revealed that although the drug companies didn’t know how to remove the hepatitis viruses and HIV, it was known but not by them. It has been known since World War II that heating plasma inactivates hepatitis viruses. If Hepatitis would have been destroyed in plasma by heating, HIV would have also been eliminated even though its existence was not known. AIDS could have been prevented in hemophilia.

In the USA the system of free marketing and capitalism leads to entrepreneurship resulting in the development of new beneficial medicines by pharmaceutical manufacturers. Remarkable and beneficial new medicines have been developed in the USA using genetic engineering methods with recombinant techniques as a result of capitalism.   The force that drives new development is profitability. But when safety is sacrificed for profitability, in a society without cost controls, greed prevails. The manufacture of medicine to treat hemophilia is a multi-billion dollar industry with intense competition.  Because of human nature regulations are necessary to prevent greed.  The families who lost a loved one from AIDS or liver failure from hepatitis regard the drug companies that made the new medicine for hemophilia as bringing great advancement but guilty of greed.

AIDS is not a mysterious disease. It is the result of HIV infection in humans when the natural occurring virus in simians in Africa, SIV, jumped a species to become HIV in humans.  This came about as the result of the production of the human hepatitis B vaccine. As the result of human behavior, the HIV virus infected intravenous drug users who sold their plasma to pharmaceutical manufacturers of the medicine to treat hemophilia.

The use of a medical treatment requires judgment by the prescribing doctor and the patient recipient.  The benefits of treatment must be compared with the hazards, a trade off. The impact of an activity, a medical treatment or a pharmaceutical innovation, may not be apparent at the time of an action. The risk of harm from a possible but unknown substance in the medicine was judged to be a less threat than the threat of death from bleeding into the brain if medicine was withheld. That turned out to be incorrect.

Sometimes good intentions result in bad things happening.  The intent to prevent hepatitis infection in Africa was a good intention. But the process led to the jumping of a species when SIV of monkeys and chimpanzees mutated to become HIV in humans.

For a balanced society, critical thinking is necessary.  Doctors are closest to their patients and should make treatment decisions, with input from their patients, without influence from pharmaceutical manufacturers and commercial and publicity organizations.

We should not forget the great tragedy that happened in hemophilia when thousands of persons all over the world died from AIDS and liver failure.  AIDS is a man-made disease and could have been avoided. Their families want their story to be told. They should be remembered so that this tragedy does not recur.   They are part of our society and all of us should care what happened to them.

Everett Winslow Lovrien is medical director of Hemophilia Center at the Oregon Health Sciences University and the author of Doctor Guilt?