Baxter Announces ADVATE Approval in China for the Treatment of Hemophilia A

DEERFIELD, Ill, May 16, 2012- Baxter International Inc. (NYSE:BAX) today announced  the approval of ADVATE [Recombinant Human Coagulation Factor VIII for injection] for the control and prophylaxis of bleeding episodes in individuals with hemophilia A (congenital factor VIII deficiency) in China by the State Food and Drug Administration (SFDA). It is estimated that more than 50,000 people in China are living with hemophilia A.

“The introduction of recombinant FVIII therapies in China offers new treatment options for hemophilia patients. The launch of ADVATE is another step in advancing hemophilia care in China,” said Professor Yang Renchi, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, the leading professional hematological institution providing basic medical research with clinical services in China.

“Great strides have been made in managing hemophilia, allowing people with this serious condition to live longer, more active and fulfilling lives than ever before,” said Guan Tao, Secretary General of Hemophilia Home, the hemophilia patient organization in China.  “The availability of ADVATE will be an important milestone for people with hemophilia in China.”

ADVATE is infused directly into the bloodstream and works by temporarily raising the level of factor VIII in the bloodstream, allowing the body’s blood clotting process to properly function. Extensive global use and multiple clinical trials demonstrate clinical evidence for ADVATE.  With SFDA’s action, ADVATE is now approved in 54 countries worldwide.

“The approval of ADVATE in China marks an important milestone for Baxter and supports our ongoing commitment to treating individuals living with hemophilia,” said Ludwig Hantson, Ph.D., president of Baxter’s BioScience business.

Baxter continues to work closely with the Chinese hemophilia community, including both patients and treaters, to provide access to care for this life-saving, life-sustaining therapy. In 2010, Baxter cooperated with the Ministry of Health to set up a “Hemophilia Disease Management System,” China’s first nationwide hemophilia patient registration and management system integrating diagnosis and treatment information. In recent years, Baxter has donated more than five million IUs of hemophilia products to Chinese patients and has provided a number of resources to raise awareness of the disease.

About ADVATE
ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method] was initially approved by the FDA in July 2003 for control and prevention of bleeding episodes in adults and children (0-16 years) with hemophilia A. ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives. Because no blood derived components are added at any stage of the manufacturing process, the potential risk of transmitting pathogens that may be carried in blood-based additives is eliminated. There have been no confirmed reports of transmission of HIV, HBV or HCV with rFVIII therapies.

ADVATE is approved in the United States, Canada, 27 countries in the European Union, Argentina, Australia, Brazil, Chile, China, Colombia, Croatia, Hong Kong, Iceland, Iraq, Japan, Macau, Malaysia, New Zealand, Norway, Panama, Puerto Rico, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Uruguay and Venezuela.

In the United States, ADVATE [Antihemophilic Factor (Recombinant) Plasma/AlbuminFree Method] is also indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children (0-16 years) with hemophilia A. ADVATE is the only antihemophilic factor approved in the United States for prophylactic use in both adults and children.  ADVATE is not indicated for the treatment of von Willebrand disease.

About Hemophilia A
Hemophilia is a rare genetic blood clotting disorder that primarily affects males.¹  People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood.¹  Two of the most common forms of hemophilia are A and B.²  In people with hemophilia A, clotting factor VIII is not present in sufficient amounts or is absent.²  Without enough FVIII, people with hemophilia can experience spontaneous, uncontrolled internal bleeding that is painful, debilitating, damaging to joints and potentially fatal.²  According to the World Federation of Hemophilia, more than 400,000 people in the world have hemophilia.¹  All races and economic groups are affected equally.¹ 

Detailed Important Risk Information for ADVATE
ADVATE is contraindicated in patients with known anaphylaxis to mouse or hamster protein or other constituents of the product.

Allergic-type hypersensitivity reactions, including anaphylaxis, are possible and have been reported with ADVATE. Symptoms have manifested as dizziness, paresthesia, rash, flushing, face swelling, urticaria, dyspnea, and pruritus. Discontinue use if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Carefully monitor patients treated with AHF products for the development of FVIII inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs).

If expected plasma FVIII levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures FVIII inhibitor concentration.

The serious adverse reactions seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to FVIII.

The most common adverse reactions observed in clinical trials (frequency greater than or equal to 10% of patients) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, and limb injury.

Please see full prescribing information for ADVATE at: www.baxter.com/downloads/healthcare_professionals/products/ADVATE_PI.pdf

About Baxter International
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 expectations with respect to the introduction and use of ADVATE in China. 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; market acceptance of ADVATE in China; 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.

1. What is Hemophilia? World Federation of Hemophilia. Accessed on: 29 June 2011. Available at: www.wfh.org/2/1/1_1_Hemophilia.htm .

2. Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: 29 June 2011. Available at: http://www.wfh.org/2/1/1_1_1_FAQ.htm#difference . 

3. Hemophilia A. National Hemophilia Foundation. Accessed on: 29 June 2011. Available at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=180&contentid=45&rptname=bleeding .

Two hemophilia drugs being developed could hold blockbuster potential

 

Novo says blood drugs could hold blockbuster potential

COPENHAGEN | Tue May 1, 2012 3:10pm BST

COPENHAGEN (Reuters) – Two hemophilia drugs being developed by Danish drugmaker Novo Nordisk could hold blockbuster potential though sales of its only hemophilia drug on the market will be flat this year, its chief science officer said.

Novo Nordisk aims for a hemophilia drug candidate, Vatreptacog, to replace at least part of the 8.3 billion crowns ($1.48 billion) in annual sales of its only hemophilia drug now in the market, NovoSeven, as sales of that drug decline.

“Vatreptacog can hopefully take over the market which NovoSeven has today,” Mads Krogsgaard Thomsen told Reuters in an interview on Tuesday.

“NovoSeven is a blockbuster today, so you can say that if Vatreptacog takes over after NovoSeven, that drug should hold blockbuster potential,” he said.

Blockbuster is a term used to describe drugs that reach annual sales above $1 billion within five years of launch.

Another of Novo Nordisk’s drug candidates, N8-GP, a long-lasting hemophilia treatment, would compete directly with products from U.S. pharmaceuticals group Baxter International Inc, which today hold blockbuster status.

“If one is lucky enough to make a long-acting N8-GP drug which is a bit better than the competing drugs, then you could be on the way to a blockbuster market, but that is too early to predict,” Thomsen said.

“But the potential is there if the profile turns out right,” he said. ($1 = 5.6205 Danish crowns)

Click here for original Reuters news release

More new drugs are in the pipeline now than in past decades

By Sarah Aldridge | 02.09.2012  by Hemaware

The marketing terms “new and improved” and “longer lasting” are not limited to the latest brand of chewing gum. They also apply to a long list of therapies now in clinical trials for people with bleeding disorders. Some people have waited years for a new recombinant product; others a lifetime for any factor product to treat their rare condition. For many, their patience is about to pay off.

There are more drugs in the pipeline now than in the past few decades. “The companies’ commitment to continue to work on behalf of patients with bleeding disorders is what’s driving it,” says Val D. Bias, CEO of the National Hemophilia Foundation (NHF). The dilemma facing many patients in the future won’t be a lack of medications, but a plethora of products that act in a variety of ways. (See table “Bleeding Disorders Drugs in Human Clinical Trials.”)

For drugs to be approved and licensed by the US Food and Drug Administration (FDA), they have to go through a series of clinical trials. First they are tested on animals, such as mice; then they are tested on humans. Each phase of a clinical trial helps determine the drug’s safety, efficacy, optimal dosage and side effects. (See sidebar, “Clinical Trial Phases.”) The National Institutes of Health clinical trials registry at clinicaltrials.gov lists more than 250 trials on hemophilia and more than 60 on von Willebrand disease (VWD). (See “Clinical Trials 101.”).)

Tried and True vs. Something New

Prophylactic medications to treat hemophilia have given patients a new degree of freedom. They can self-infuse whenever and wherever it’s convenient.

“In terms of hemophilia A and B, I feel that the products we have right now are really good,” says Marion Koerper, MD, NHF medical advisor. She is also director emerita of the hemophilia treatment center at the University of California, San Francisco, where she practices pediatric hematology and oncology. “The factors do work to stop bleeding or, in the case of prophylaxis, prevent bleeding.”

However, prophylaxis is not perfect. “It’s only efficacious if the patient takes it the prescribed way,” Koerper says. The best time to give factor is in the morning before school or work, often the most hectic time of day. For busy families who delay treatment until bedtime, there are consequences. “That is not optimal because the child’s highest levels are while he’s asleep, rather than when he’s running around with his pals on the playground,” says Koerper.

Further, taking a product two or three times a week means that clotting strength can plummet on the off days. “When we give prophylaxis right now for a hemophilia A patient, we’re resolved to the fact that before their next prophy dose, their level in plasma could be as low as about 1% to 2%,” says Steven W. Pipe, MD, medical director, Pediatric Hemophilia and Coagulation Disorders Program, University of Michigan, Ann Arbor. That puts patients at risk for bleeding, especially if there is trauma. “Clearly, that’s not correction of their hemostasis.”

Products With Staying Power

To remedy that risk, pharmaceutical companies are creating new products that last longer in the bloodstream. The amount of factor VIII (FVIII) or factor FIX (FIX) in the blood is measured by its half-life, the time it takes for the amount of factor to be reduced by half. There are many variables involved, including blood type, but FVIII’s half-life is about 8–12 hours; FIX’s is about 18–24 hours. One option is to increase the interval between prophylactic doses, ideally to once a week for FIX products and twice a week for FVIII products. 

Another option is to retain the current prophylactic regimen, but avoid the precipitous drop in clotting factor as the next dosing time approaches. “We may be able to maintain much higher plasma levels than we’ve been able to previously with the same intervals that we’re currently using,” says Pipe.

One way to prevent factor products from degrading too quickly is to attach them to the chemical compound polyethylene glycol (PEG). This process, called PEGylation, increases the size of the factor protein molecule so that it circulates in the blood longer and is not cleared by the kidneys prematurely.

“Another strategy is to fuse the recombinant factor protein molecule to a partner protein that already has a long half-life,” says Pipe. Two naturally occurring partner proteins being fused to the FVIII or FIX molecule are albumin, which moves small molecules through the bloodstream, and Fc, a protein fragment that facilitates binding and recycling of immunoglobulin G (IgG).

Data from early clinical trials on Biogen Idec’s recombinant FVIII and FIX Fc fusion products, rFVIIIFc and rFIXFc, look promising. The A-LONG study on patients with severe hemophilia A showed a 1.7-fold increase in half-life during phase 1/2a clinical trials. B-LONG studies on patients with severe hemophilia B showed a nearly threefold increase in half-life during phase 1/2 trials. (See “Long Strides,” HemAware Summer 2011, p. 14.)

Adjunctive therapies, or drugs that are added to the primary factor product, are also being tested in clinical trials. Some use molecules that bind to tissue factor pathway inhibitor (TFPI), preventing it from hindering the action of FXa and thrombin, necessary for clot initiation and formation. Baxter’s BAX513 uses fucoidan, a seaweed extract being tested on healthy volunteers without hemophilia.

“If you block the proteins that are slowing down coagulation, you can actually restore normal clotting in hemophilic plasma without replacing the missing clotting factor,” says Pipe. For some patients, the adjunctive therapy may become the primary therapy, reducing the number of infusions needed, he says. A bonus is that some TFPI antagonists could be taken orally, such as the capsule form that delivered fucoidan to trial subjects.

“Compliance with bleeding disorders’ treatment is always an issue,” says Bias. “A drug that works better, faster and that you have to take less often can only improve that.”

Innovations for Inhibitors

An estimated 25% of patients with severe hemophilia A develop antibodies, called inhibitors, to the infused factor. Currently, patients undergo immune tolerance therapy to desensitize their immune systems or take a bypassing agent, such as FVIIa. The main drawbacks of the recombinant FVIIa product are that its half-life is only two hours and it is very expensive.

Inspiration Biopharmaceuticals is developing a recombinant porcine (pig) FVIII product for patients with inhibitors. “You can give a dose and get the measurable level of FVIII. That’s a distinct advantage when there’s a life-threatening­ bleed, like a head bleed (intracranial hemorrhage), or a limb-threatening bleed in someone with a compartment syndrome (increased pressure in a muscle in an enclosed space),” Koerper says. But because 80% of patients developed antibodies to plasma-derived pig factor within five days or after five doses, it is possible that a similar scenario might occur with the recombinant product. Results of the clinical trials will provide more data, but its use will probably be restricted.

The longer-lasting products may have an added benefit for inhibitor patients. “Some forms of PEGylation strategy and possibly even some of the fusion proteins may result in reduced risk for inhibitors,” says Pipe. Another product now being tested, Octapharma’s recombinant human-cl rhFVIII, may reduce the rate of inhibitor development because it uses proteins from human cells, not the typical hamster cells.

Recombinant VWD Product at Last

Recombinant products to treat FVIII and FIX were approved in 1992 and 1998, respectively; not so for von Willebrand factor (VWF). “It has bothered me for almost 20 years that I couldn’t offer a recombinant VWF product to my VWD patients,” says Koerper. That need will be fulfilled once Baxter’s recombinant VWF product goes through FDA approval and licensure. It will be targeted to patients with type 3 VWD, the most severe form, and those unresponsive to DDAVP, a synthetic hormone used to prevent or stop bleeds.

Gene Therapy Revisited

Researchers can now create precision drugs that treat diseases caused by specific genetic mutations. One such drug in phase 2 trials is Ataluren (PTC 124^®), manufactured by PTC Therapeutics Inc. It will be used for the approximately 10%–15% of patients with hemophilia A and B with a nonsense mutation, which halts factor production early. Ataluren introduces a molecule that allows the cell to read through the stop signal, making more clotting factor. It comes in a powder that is mixed in water. “Something that you can swallow is going to be a huge advantage because there are no needles involved,” Koerper says. (See sidebar “The Allure of Ataluren” in “What’s Your Genotype?” HemAware Spring 2010, p. 29.)

Rare Bleeding Disorders on the Radar

Patients with rare factor deficiencies know that being one in a million is hardly a cause for celebration. “People forget that there are other clotting factor deficiencies that, in some cases, have no treatment,” says Bias.

But hope is on the horizon. Companies that fractionate, or separate, plasma are interested in getting as many products out of it as they can, says Pipe. “Developing new markets for new plasma derivatives, such as the new FXIII product Corifact™ (approved by the FDA in March 2011), and RiaSTAP^®, a fibrinogen concentrate to treat FI deficiency (indicated for patients with congenital fibrinogen deficiency including afibrinogenemia and hypofibrinogenemia only), increases the sustainability and viability of the plasma fractionation industry.” Both products are manufactured by CSL Behring. Currently, Novo Nordisk has applied for a license for its recombinant FXIII product. British Plasma Laboratories has a plasma-derived FX product in phase 3 clinical trials.

“NHF is most supportive of new products for rare disorders or categories where products don’t currently exist, like the recombinant VWD product,” Bias says. “It’s important that people have access to a product that’s made for them.”

Time Frame for Trials

For drugs now in clinical trials, that access may take a few years. “From initiation of clinical trials to approval, it’s about a five-year window,” says Pipe. Drugs nearing the finish line—those in phase 3 or moving to FDA licensing—still have between 18 and 30 months, he says.

New Era of Optimism

Patients awaiting better, more effective or first-time products to treat their bleeding disorders have many reasons to be optimistic. “For the first time we’re now going to be offering agents that clearly behave differently. We’re not going to be faced with just a single-breed entity to choose from,” Pipe says.

The idea of having more distinct options may be foreign to some, but should be very welcome. New products with different mechanisms mean that treatments may soon be given in a more targeted, personalized manner. “When you have multiple choices it’s going to take some time for the clinicians and families to figure out what’s best for individual patients,” Pipe says.

When recombinant FVIII and FIX drugs came out two decades ago, Koerper thought they were the “ultimate products.” But with all of these recent innovations, she’s changed her thinking. “Now I realize there is so much more that can be done.”

—————————————————————————

Clinical Trial Phases

A drug must go through several stages of testing, called “phases” in clinical trials, before it can seek approval review by the Food and Drug Administration (FDA) for use in the US. Depending on how well things go in each phase, the drug progresses from one phase to the next. However, some drug trials are halted voluntarily or by the FDA at certain stages because of concerns about safety or efficacy, for instance. It can take up to five years or more for a new drug to pass muster and make it to the marketplace.

Phase 1

An experimental drug is given to a small number of people (20–100*) to test its safety, tolerability, pharmacokinetics (absorption, distribution, metabolism and excretion) and pharmacodynamics (biochemistry and physiology). Dose-escalating studies are done during this phase to find the optimal dosage.

Phase 2

The drug is given to a larger number of people (100–300*) to evaluate its effectiveness and safety.

Phase 3

The drug is tested in an even larger group of people (1,000–3,000*) at multiple centers across the country to confirm its effectiveness and safety compared with current treatments. During this phase, side effects are also monitored. The studies are randomized and controlled, meaning some patients receive the drug and others get a placebo. Once this “pivotal phase” is successfully completed, the manufacturer can apply for licensing review by the FDA.

Phase 4

Once a drug is licensed for sale, post-marketing surveillance trials are required by the FDA. These trials provide important information on risks, including less common side effects, benefits and optimal use.

*Note: these figures are for standard clinical trials. For bleeding disorders products, the number of trial subjects is often much smaller.

Information partially adapted from clinicaltrials.gov.

Bleeding Disorders Drugs in Human Clinical Trials*

Bleeding Disorder	Drug Name	Company	Clinical Trial
Hemophilia A	Recombinant FVIII-Fc Fusion	Biogen Idec	Phase 3
	NN7088 Recombinant FVIII, third generation	Novo Nordisk	Phase 3
	Human-cl rhFVIII (recomb FVIII, human cell line)	Octapharma	Phase 3
	OBI-1 Recombinant Porcine FVIII	Inspiration	Phase 2/3
	ARC 19499 PEG-conjugated aptamer	Archemix	Phase 1/2
	BAX499 FVIII, subcutaneous	Baxter	Phase 1
	CSL627 Recombinant FVIII-single chain	CSL Behring	Phase 1
Hemophilia B	BAX326 Recombinant FIX	Baxter	Phase 3
	Recombinant FIX-Fc Fusion	Biogen Idec	Phase 3
	OB1001 Recombinant FIX	Inspiration	Phase 2/3
	NN7999 Glyco-PEGylated Recombinant FIX	Novo Nordisk	Phase 3
	ARC 19499 PEG-conjugated aptamer	Archemix	Phase 1/2
	BAX499 FIX, subcutaneous	Baxter	Phase 1
	CSL654 Recombinant FIX-Albumin Fusion	CSL Behring	Phase 1/2
Hemophilia A & B Nonsense mutation	PTC 124 Ataluren	PTC	Phase 2
Inhibitors	rFVII analog	Novo Nordisk	Phase 3
	CSL689 Recombinant FVII-Albumin Fusion	CSL Behring	Phase 2
	GlycoPEG-rFVIIa	Novo Nordisk	Phase 2
	SQ GlycoPEG-rFVIIa	Novo Nordisk	Phase 1
Von Willebrand Disease	BAX 111, rVWF	Baxter	Phase 3
Rare Factor Deficiencies	Recombinant FXIII	Novo Nordisk	License applied for
	Plasma-derived FX	BPL	Phase 3

*This table provides a sampling of drugs now in clinical trials to treat various bleeding disorders. It is by no means comprehensive. NHF does not endorse or recommend any of the products or manufacturers listed. To check the status of drugs now in clinical trials, visit clinicaltrials.gov.

Search this blog for more information on individual press releases form Baxter, Novo Nordisk, CSL Behring,  OctaPharma, Biogen Idec, and Isporation Biopharmaceuticals.

Investigational BAX 855 is based on ADVATE Factor VIII Molecule

DEERFIELD, Ill.–(BUSINESS WIRE)–Jan. 5, 2012–
Baxter International Inc. (NYSE: BAX) today announced the dosing of the first patients in a Phase I clinical trial of its lead investigational candidate, BAX 855, a longer-acting (PEGylated) form of a full-length recombinant factor VIII (rFVIII) protein. BAX 855 is based on Baxter’s ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method] full-length rFVIII molecule and plasma/albumin-free (PAF) manufacturing process.

The Phase I trial is a prospective, open-label study that will assess the safety, tolerability and pharmacokinetics of BAX 855 in previously-treated patients aged 12 years or older with severe hemophilia A. When used for prophylaxis, Baxter s ADVATE requires patients to infuse every two to three days to reduce the occurrence of bleeding episodes. This Phase I trial is the first step in assessing whether BAX 855 can be infused less frequently.

This trial is designed to provide new insights about our investigational longer-acting FVIII molecule, BAX 855, with the ultimate goal of improving care for patients living with hemophilia A, said Prof. Hartmut J. Ehrlich, M.D., vice president of global research and development in Baxter s BioScience business. The Phase I results will serve as the foundation for advancing this important program through clinical development and determining whether BAX 855 can offer a treatment regimen requiring fewer infusions than ADVATE.

 BAX 855 employs Baxter s proprietary full-length plasma/albumin-free recombinant protein platform that does not contain any human or animal-derived additives. BAX 855 leverages Nektar Therapeutics (NASDAQ: NKTR) proprietary PEGylation technology, which is designed to extend the duration of activity of proteins and larger molecules. Baxter and Nektar have a collaboration to develop PEGylated products designed to provide new long-acting therapies for hemophilia patients.

ADVATE was recently approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A. With the inclusion of prophylaxis in the adult patient population, ADVATE became the only antihemophilic factor approved in the United States for prophylactic use in both children and adults. This approval was supported by a Phase IV prophylaxis study sponsored by Baxter demonstrating that ADVATE for routine prophylaxis significantly reduced median annual bleed rates (ABR) in hemophilia A patients. In the study, patients experienced 44 bleeds (per patient per year) during on-demand treatment compared to one bleed (per patient per year) while on either of the prophylactic regimens evaluated, a 98 percent reduction in annual bleed rate (p<0.0001). Nearly half (42 percent) of patients experienced zero bleeding episodes during one year on prophylactic therapy. Evaluable patients were those with at least 90 percent adherence to their prescribed prophylactic regimen.

 About ADVATE

ADVATE was initially approved by the FDA in July 2003 for control and prevention of bleeding episodes in adults and children with hemophilia A.

ADVATE (derived from the complete FVIII gene) is a recombinant FVIII therapy that is processed without any blood-based additives. Because no blood-derived components are added at any stage of the manufacturing process, the potential risk of transmitting pathogens that may be carried in blood-based additives is eliminated. There have been no confirmed reports of transmission of HIV, HBV or HCV with rFVIII therapies.

 ADVATE is approved in 53 countries worldwide including the United States, Canada, 27 countries in the European Union, Argentina, Australia, Brazil, Chile, Colombia, Croatia, Hong Kong, Iceland, Iraq, Japan, Macau, Malaysia, New Zealand, Norway, Panama, Puerto Rico, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Uruguay and Venezuela. Since the initial approval of ADVATE, more than 10 billion international units have been distributed, and ADVATE is the number one chosen rFVIII worldwide.

ADVATE is an Antihemophilic Factor (Recombinant) indicated for:

• Control and prevention of bleeding episodes in adults and children
  (0-16 years) with hemophilia A
• Routine prophylaxis to prevent or reduce the frequency of bleeding
  episodes in adults and children (0-16 years) with hemophilia A
• Perioperative management in adults and children (0-16 years) with
  hemophilia A
• ADVATE is not indicated for the treatment of von Willebrand disease

Important Risk Information for ADVATE

 ADVATE is contraindicated in patients with known anaphylaxis to mouse or
hamster protein or other constituents of the product. Allergic-type hypersensitivity reactions, including anaphylaxis, are possible and have been reported with ADVATE. Symptoms have manifested as dizziness, paresthesia, rash, flushing, face swelling, urticaria, dyspnea, and pruritis. Discontinue use if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Carefully monitor patients treated with AHF products for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have been reported following administration of ADVATE predominantly in previously-untreated patients (PUPs) and previously minimally-treated patients (MTPs).

If expected plasma FVIII levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

The serious adverse drug reactions (ADRs) seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to Factor VIII. The most common ADRs observed in clinical trials (frequency = 10 percent of patients) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, and limb injury.

Please see full prescribing information at www.advate.com.

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 trial of the Company s investigational compound BAX 855, including with respect to expectations related to clinical outcomes. 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: timely submission and approval of anticipated regulatory filings; clinical results validating the use of BAX 855 to treat patients with severe hemophilia A; satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; and other risks identified in Baxter’s most recent filing on Form 10-K and other SEC filings, all of which are available on the company’s website. Baxter does not undertake to update its forward-looking statements.

1. What is Hemophilia? World Federation of Hemophilia. Accessed on: 29 June 2011. Available at: http://www.wfh.org/2/1/1_1_1_What_Is_Hemophilia.htm

2. Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: 24 August 2011. Available at: http://www.wfh.org/index.asp?lang=EN

3.  Hemophilia A. National Hemophilia Foundation. Accessed on: 29 June 2011. Available at http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=180&contentid=45&rptname=bleeding.

Source: Baxter International Inc.

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FDA Approves Baxter’s ADVATE as the Only FVIII for Routine Prophylaxis in Both Adults and Children with Hemophilia A

Press Release from BAXTER

ADVATE for routine prophylaxis reduced annual bleed events in hemophilia A patients from forty-four to one as compared to an on demand regimen in a clinical study

Once every third day pharmacokinetic dosing option offers some patients the opportunity for fewer infusions annually

DEERFIELD, Ill., December 16, 2011 – Baxter International Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method] for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A.  ADVATE is the only antihemophilic factor approved in the United States for prophylactic use in both adults and children. 

The approval is based on a Phase IV prophylaxis study sponsored by Baxter demonstrating that ADVATE for routine prophylaxis significantly reduced median annual bleed rates (ABR) in hemophilia A patients from 44 to one as compared to an on-demand regimen.  Forty-two percent of study patients experienced zero bleeds during one year on prophylaxis.  Of the two prophylactic regimens approved for use, the dosing schedule of every three days, a pharmacokinetic-driven regimen based on patient’s clinical response, offered some patients the option of fewer infusions over one year of treatment. 

“Emerging data provide important information to help physicians optimize care for hemophilia patients of all ages by preventing unexpected bleeding events that can have a detrimental impact on the lives of patients,” said Leonard Valentino, M.D., Director, Rush Hemophilia and Thrombophilia Center and Section of Pediatric Hematology/Oncology, Rush University Medical Center, Chicago, and lead investigator of this study. “These data confirm the important clinical benefits of ADVATE when used as a prophylactic therapy to reduce bleeding episodes.”

The study findings demonstrated a statistically significant reduction in the median annual bleeding rate, with patients experiencing 44 bleeds (per patient per year) during on-demand treatment compared to one bleed (per patient per year) while on either of the prophylactic regimens evaluated, a 98 percent reduction in annual bleed rate (p<0.0001).  Nearly half (42 percent) of patients experienced no bleeding episodes while on one year of prophylactic treatment.  Evaluable patients had greater than or equal to 90 percent adherence to the prescribed prophylactic regimen.  While the trial was not powered to demonstrate equivalence in bleeding rate between the two prophylaxis arms, there was no statistically significant difference in bleeding frequency observed between the two prophylaxis regimens studied.

“This latest clinical milestone for ADVATE is an important step forward for people living with hemophilia A as we continue to research ways to advance care for this patient population,” said Bruce Ewenstein, M.D., Ph.D, vice president, clinical affairs, Baxter’s BioScience business. “This rigorous clinical study demonstrated that the number of bleeding episodes experienced each year could be reduced to as low as one event with prophylactic treatment.  Further, the pharmacokinetic-driven dosing regimen based on patient’s clinical response every third day, offers some patients the option of fewer infusions over one year of treatment than the current standard prophylaxis regimen.”

For the prophylaxis regimen to prevent or reduce frequency of bleeding episodes, ADVATE dosing of three to four times weekly (between 20 to 40 international units of factor VIII per kg body weight every other day) may be used.  Alternatively, an every third day dosing regimen targeted to maintain FVIII trough levels greater than or equal to one percent may be employed.  The serious adverse drug reactions (ADRs) seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to Factor VIII.  The most common ADRs observed in clinical trials (frequency ≥ 10% of patients) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, limb injury.

Study Design
The approval is based on the ADVATE Phase IV study comparing two prophylactic regimens to on demand treatment of bleeding episodes in previously treated patients with severe or moderately severe hemophilia A.  The multi-center, open-label, prospective, randomized, controlled clinical trial evaluated the relative efficacy of ADVATE use in two prophylactic regimens (standard prophylaxis [20-40 international units/kg every 48 hours] and pharmacokinetic-driven prophylaxis [20-80 international units/kg every 72 hours, targeted to maintain FVIII trough levels at least 1 percent or higher]) compared to that of on-demand treatment in 53 previously treated patients with severe to moderately severe hemophilia A.  Initial treatment with six months of on-demand therapy was followed by 12 months of either prophylactic regimen.

All patients had a history of at least eight joint hemorrhages per year prior to entering the study.  Additionally, each patient evaluated was adherent to greater than 90 percent of the prescribed number of prophylactic infusions, and no patient in the study surpassed the upper boundary of 110 percent of the prescribed number of prophylactic infusions.

About ADVATE
ADVATE was initially approved by the FDA in July 2003 for control and prevention of bleeding episodes in adults and children with hemophilia A.  ADVATE (derived from the complete FVIII gene) is a recombinant FVIII therapy that is processed without any blood-based additives.  Because no blood-derived components are added at any stage of the manufacturing process, the potential risk of transmitting pathogens that may be carried in blood-based additives is eliminated.  There have been no confirmed reports of transmission of HIV, HBV or HCV with any rFVIII therapies.

ADVATE is approved in 52 countries worldwide including the United States, Canada, 27 countries in the European Union, Argentina, Australia, Brazil, Chile, Colombia, Croatia, Hong Kong, Iceland, Iraq, Japan, Macau, Malaysia, New Zealand, Norway, Puerto Rico, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Uruguay and Venezuela. Since the initial approval of ADVATE eight years ago, nearly 10 billion international units have been distributed, and ADVATE is the number one chosen rFVIII worldwide.

ADVATE is an Antihemophilic Factor (Recombinant) indicated for:

• Control and prevention of bleeding episodes in adults and children (0-16 years) with Hemophilia A
• Perioperative management in adults and children (0-16 years) with hemophilia A
• Routine prophylaxis to prevent or reduce frequency of  bleeding episodes in adults and children (0-16 years) with hemophilia A
• ADVATE is not indicated for the treatment of von Willebrand disease

Detailed Important Risk Information for ADVATE
ADVATE is contraindicated in patients with known anaphylaxis to mouse or hamster protein or other constituents of the product.

Allergic-type hypersensitivity reactions, including anaphylaxis, are possible and have been reported with ADVATE.  Symptoms have manifested as dizziness, paresthesia, rash, flushing, face swelling, urticaria, dyspnea, and pruritus.  Discontinue use if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Patients treated with AHF products should be monitored for the development of FVIII inhibitors.  Inhibitors have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs).

If expected plasma FVIII levels are not attained, or if bleeding is not controlled with an expected dose, test for the presence of inhibitors.

The most serious adverse reactions seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to FVIII.

The most common adverse reactions observed in clinical trials (frequency less than 10% of patients) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, and limb injury.

Please see full prescribing information at www.baxter.com/downloads/healthcare_professionals/products/ADVATE_PI.pdf.

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

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.
1. What is Hemophilia? World Federation of Hemophilia. Accessed on: 29 June 2011. Available at: http://www.wfh.org/2/1/1_1_Hemophilia.htm .
2. Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: 29 June 2011.  Available at: http://www.wfh.org/2/1/1_1_1_FAQ.htm#difference .
3. Hemophilia A. National Hemophilia Foundation. Accessed on: 29 June 2011. Available at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=180&contentid=45&rptname=bleeding .

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.

 

FEIBA drug safe and effective for patients with hemophilia A

November 3rd, 2011

An international research team led by Dr. Cindy Leissinger of Tulane University School of Medicine, along with Dr. Alessandro Gringeri from the University of Milan, has found that a drug commonly used to treat bleeding events in people with a type of severe hemophilia can also be used to prevent such events from happening in the first place. The study, the first to confirm the efficacy and safety of the drug FEIBA™ in bleed prevention is published in the November 3, 2011 issue of The New England Journal of Medicine.

The study examined the ability of FEIBA to prevent bleeds in people with severe hemophilia A with inhibitors. People with this condition produce antibodies known as inhibitors. These inhibitors render ineffective the usual treatment for hemophilia, which involves replacement of the blood clotting factor (Factor VIII) that is absent in hemophilia patients. Approximately 30 percent of patients with severe hemophilia A develop such “inhibitor” antibodies. Hemophilia A patients with inhibitors require treatments with alternate forms of clotting factor concentrates, known as bypassing agents, and until recently primarily had to be infused with clotting factors “on demand” as bleeding episodes occur. Treatment of bleeding events in these patients is not always effective, leading to significant problems for patients, who typically experience repeated joint bleeding and progressive joint disease.

The Tulane-led study tested if preventive treatment with the bypassing agent FEIBA is safe and effective in preventing joint and other bleeds in hemophilia A patients with inhibitors. Thirty-four patients were enrolled for the 15-month-long study.

The study showed that, compared to on-demand therapy, FEIBA infused three times per week resulted in an overall reduction of 62 percent in all bleeding events and a 72 percent reduction in target joint bleeding (“target joints” are joints that experience repetitive bleeding). Nearly two-thirds of patients showed a very good response to preventive FEIBA treatment, experiencing a reduction in bleeding events of 82 percent.

Source: The New England Journal of Medicine

For more information follow attached link, here.

Factor VIII Biopump

 From Reuters

Medgenics says in talks with Baxter on collaboration

Fri Oct 14, 2011 10:49am EDT

Oct 14 (Reuters) – Medgenics Inc said on Friday it is in active discussions with Baxter International Inc regarding a possible further collaboration on a medical device.

Medgenics and Baxter had an agreement, which expired on Sept. 30, 2011, for the joint development of the Factor VIII Biopump, a proprietary tissue-based platform technology that delivers therapeutic proteins using the patient’s own skin biopsy.

The pump would be used to treat a range of chronic diseases including anemia, hepatitis C and hemophilia, Medgenics said.

No further information was provided and Baxter was not immediately available to comment.

Another post from Bleedingdisorder about Medgenics and their “Biopump” can be found here.

Baxter Initiates Phase III Trial of Investigational BAX 111 For the Treatment of von Willebrand Disease

First Recombinant Product in Clinical Development for Most Common Inherited Bleeding Disorder

DEERFIELD, Ill.–(BUSINESS WIRE)–Baxter International Inc. today announced initiation of a Phase III clinical trial to evaluate the safety and effectiveness of BAX 111, Baxter’s investigational recombinant von Willebrand factor (rVWF), for the treatment and prevention of bleeding episodes in patients with von Willebrand disease. This condition is the most common type of inherited bleeding disorder, affecting both men and women, the majority of whom are undiagnosed due to mild symptoms.¹ BAX 111 is the first recombinant von Willebrand product in clinical development.

“Currently available treatments that are effective for von Willebrand disease are produced from human plasma. Baxter’s investigational rVWF does not contain blood-based additives,” said Bruce Ewenstein, M.D., Ph.D., vice president, Clinical Affairs in Baxter’s BioScience business. “The initiation of the BAX 111 Phase III trial represents a significant step forward as the product, if proven safe and effective, may lead to an alternative treatment choice for clinicians and their patients with von Willebrand disease.”

The Phase III multicenter, open-label clinical trial is enrolling patients with severe von Willebrand disease and will assess the safety, effectiveness and pharmacokinetics of BAX 111 for the prevention and treatment of bleeding episodes. The primary endpoint is the number of patients experiencing treatment success for treated bleeding episodes. The trial will also assess changes in health-related quality of life (HRQoL) associated with the treatment. Standardized measures will be used to assess the overall impact of six months of recombinant treatment on the physical, emotional and social functioning of patients with von Willebrand disease.

The study will assess a minimum of 36 patients in trial sites in the United States, Canada, Europe, Australia, Japan and India. Information about the trial including enrollment is available at www.clinicaltrials.gov or by calling 1-805-372-3322.

About Recombinant Von Willebrand Factor (rVWF)

Baxter’s investigational rVWF concentrate was developed using a plasma- and albumin-free manufacturing method. It is the first recombinant replacement protein in clinical development for von Willebrand disease. Both the European Commission and the U.S. Food and Drug Administration granted orphan designation for Baxter’s rVWF in November 2010.

About von Willebrand Disease¹

Von Willebrand disease is the most common inherited bleeding disorder and affects both men and women. Patients with von Willebrand disease either produce insufficient von Willebrand factor or carry defective von Willebrand factor that result in problems with forming clots to stop bleeding, particularly in the skin and mucous membranes such as in the gastrointestinal (GI) tract. It is estimated that up to one percent of the world’s population suffers from von Willebrand disease, but because many people have only mild symptoms, they may not know they have the condition. Research has suggested that as many as nine out of 10 people with von Willebrand disease have not been diagnosed.

About Baxter International Inc.

Baxter International Inc. (NYSE: BAX), 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 BAX 111, the Company’s investigational recombinant von Willebrand factor. 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; additional clinical results demonstrating the safety and efficacy of BAX111; the successful completion of the Phase III trial; actions of regulatory bodies and other governmental authorities; and other risks identified in the company’s most recent filing on Form 10-K and other SEC filings, all of which are available on the company’s website. The company does not undertake to update its forward-looking statements.

1. The Basic Science, Diagnosis, and Clinical Management of von Willebrand Disease (2008)
http://www.wfh.org/2/docs/Publications/VWD_WomenBleedingDisorders/TOH-35_VWD_%20Revision2008.pdf

 

Contacts

Baxter International Inc.
Media Contacts:
Deborah Spak, (847) 948-2349
Marie Kennedy, (805) 372-3543
or
Investor Contacts:
Mary Kay Ladone, (847) 948-3371
Clare Trachtman, (847) 948-3085

Safety and Efficacy of rVWF in the Treatment and Prevention of Bleeding Episodes in VWD

The purpose of this Phase 3 study is to assess the pharmacokinetics of rVWF:rFVIII and rVWF, and to assess the safety and efficacy of rVWF:rFVIII and rVWF in the treatment and prevention of bleeding events in subjects with severe hereditary von Willebrand disease (VWD)…

Brief Summary

Official Title: “A Phase 3 Clinical Study to Determine the Safety and Efficacy of rVWF:rFVIII and rVWF in the Treatment and Prevention of Bleeding Episodes in Subjects Diagnosed With Von Willebrand Disease”

The purpose of this Phase 3 study is to assess the pharmacokinetics of rVWF:rFVIII and rVWF, and to assess the safety and efficacy of rVWF:rFVIII and rVWF in the treatment and prevention of bleeding events in subjects with severe hereditary von Willebrand disease (VWD).

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
• Study Primary Completion Date: February 2013

Intervention(s) in this Clinical Trial

• Biological: Recombinant von Willebrand factor (rVWF) with or without rFVIII (Advate)
  • Intravenous administration

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: PK 80 Arm (20 subjects with severe VWD)
  • PK assessment (80 IU/kg rVWF) + 12-month treatment period
• Experimental: PK 50 Arm (14 subjects with type 3 VWD)
  • Two single-blinded PK assessments (50 IU/kg rVWF + rFVIII/placebo) + 12-month treatment period

Outcome Measures for this Clinical Trial

Primary Measures

• Number of subjects with treatment success for treated bleeding episodes
• Time Frame: 12 months
  Safety Issue?: No

Criteria for Participation in this Clinical Trial

Selected Inclusion Criteria:

• The subject has been diagnosed with type 3 von Willebrand disease (VWD:Ag <= 3 IU/dl) or severe non-type 3 VWD (VWF:RCo < 20 IU/dL) or type 2N VWD (FVIII:C <10% and documented genetics)
• The subject has had a minimum of 6 documented bleeds (medical history) requiring VWF coagulation factor replacement therapy during the previous 2 years prior to enrollment
• The subject is at least 18 and not older than 65 years of age at enrollment

Selected Exclusion Criteria:

• The subject has been diagnosed with a hereditary or acquired coagulation disorder other than VWD (e.g. qualitative and quantitative platelet disorders or elevated
• PT/international normalized ratio [INR] > 1.4)
• The subject has a documented history of a VWF:RCo half-life of < 6 hours
• The subject has a history or presence of aVWF inhibitor at screening
• The subject has a history or presence of a factor VIII (FVIII) inhibitor with a titer
• >= 0.4 BU (by Nijmegen assay) or >= 0.6 BU (by Bethesda assay)

Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: 65 Years
Are Healthy Volunteers Accepted for this Clinical Trial?: No

Clinical Trial Investigator Information

Lead Investigator: Baxter Healthcare Corporation Industry

Overall Clinical Trial Officials and Contacts

Tobias Suiter, MD Study Director Baxter Innovations GmbH  
Overall Contact: Jorge Escobar, Clinical Project Manager  jorge_escobar@baxter.com

Additional Information

Information obtained from ClinicalTrials.gov on August 04, 2011
Link to the current ClinicalTrials.gov record here.
Study ID Number: 071001
ClinicalTrials.gov Identifier: NCT01410227