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.”

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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.

Samsung Biologics and Biogen Idec Announce Formation of Biosimilars Joint Venture Samsung Bioepis

SEOUL, South Korea & WESTON, Mass.–(BUSINESS WIRE)–Feb. 27, 2012– Samsung Biologics and Biogen Idec announced today that the companies have established their joint venture, Samsung Bioepis Co., Ltd., to develop, manufacture and market biosimilars in keeping with their agreement announced in December.

Christopher Hansung Ko, previously Senior Vice President of Samsung Strategic Business Development, has been named the CEO of Samsung Bioepis. The joint venture’s Board of Directors will consist of five directors and one auditor.

The strategic collaboration between Samsung Biologics and Biogen Idec will enable Samsung Bioepis to build the capabilities needed to develop high-quality biosimilars.

Construction of Samsung Bioepis’ research and development center, located at Samsung Biologics’ site in Song-do Incheon, Korea, has started and will be completed by the end of the year.

About Samsung

Samsung is composed of companies in a wide range of business from consumer electronics to finance and insurance. Samsung was founded in 1938, and its revenue in 2010 was 255 trillion won($220 billion). In May 2010, Samsung announced the biopharmaceutical sector as one of five new strategic businesses that would lead the group’s future growth, committing to invest 2.1 trillion won($2 billion) in biopharmaceuticals by 2020. For more information about the company, please visit www.samsung.com.

About Biogen Idec

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

Click here for the entire Press Release.

Fc Fusion technology Video

Follow the link for a YouTube video on how Fc Fusion technology works to make Factor proteins last longer in the human body.

http://youtu.be/dlUYLacyUk0?hd=1

 

Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of rFVIIIFc in Paediatric Patients With Hemophilia A

This is an open-label, multi-centre study evaluating the safety, pharmacokinetic (PK) and efficacy of rFVIIIFc in previously treated peadiatric subjects with severe hemophilia A…

Brief Summary

Official Title: “Kids ALONG – An Open-Label, Multicentre Evaluation of Safety, Pharmacokinetics, and Efficacy of Recombinant Coagulation Factor VIII Fc Fusion Protein, BIIB031, in the Prevention and Treatment of Bleeding Episodes in Pediatric Subjects With Hemophilia A”

This is an open-label, multi-centre study evaluating the safety, pharmacokinetic (PK) and efficacy of rFVIIIFc in previously treated peadiatric subjects with severe hemophilia A.

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

Detailed Clinical Trial Description

Subjects will follow either a regimen of PK assessments, followed by a twice weekly prophylactic treatment with rFVIIIFc, or proceed directly to twice weekly prophylactic treatment.

Intervention(s) in this Clinical Trial

• Drug: rFVIIIFc
  • type IV administration recombinant coagulation factor VIII Fc fusion protein

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: All patients
  • prophylaxis

Outcome Measures for this Clinical Trial

Primary Measures

• Frequency of inhibitor development
  • Time Frame: 30 Weeks
    Safety Issue?: Yes

Secondary Measures

• Number of annualised bleeding episodes
  • Time Frame: 30 Weeks
    Safety Issue?: Yes

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Severe hemophilia A defined as <1 IU/dL (<1%).
• Male, <12 years of age and weight ≥13 kg.
• History of at least 50 prior exposure days to FVIII
• No current, or history of, inhibitor development to FVIII

Exclusion Criteria:

• History of anaphylaxis associated with any FVIII or IV immunoglobin administration

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 11 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Clinical Trial Investigator Information

Lead Investigator: Biogen Idec Industry

Additional Information

Information obtained from ClinicalTrials.gov on October 27, 2011

Link to the current ClinicalTrials.gov record. 

Study ID Number: 8HA02PED

ClinicalTrials.gov Identifier: NCT01458106

Health Authority: United States: Food and Drug Administration

Biogen Idec and Swedish Orphan Biovitrum Present Data on Long-Lasting Recombinant Factor VIII Therapy

KYOTO, Japan, Jul 26, 2011 (BUSINESS WIRE) –

Biogen Idec (NASDAQ: BIIB) and Swedish Orphan Biovitrum (STO: SOBI) today announced Phase 1/2a trial data showing that the companies’ long-lasting fully-recombinant factor VIII Fc fusion protein (rFVIIIFc) was well tolerated and demonstrated an approximately 1.7-fold increase in half-life compared with Advate^(R) (antihemophilic factor recombinant, plasma/albumin-free method, rFVIII), a commercially-available factor VIII product, in 16 previously-treated patients with severe hemophilia A. The findings, which were seen consistently across all patients and dose levels, are being presented today at the XXIIIrd Congress of the International Society on Thrombosis and Haemostasis in Kyoto, Japan.

“This trial is a step toward addressing the significant unmet need for a long-lasting recombinant factor VIII product,” said Neil Josephson, M.D., Co-Principal Investigator of the Phase 3 rFVIIIFc A-LONG trial and associate professor of Medicine in the Division of Hematology at the University of Washington School of Medicine, Seattle, Wash. “Results from the Phase 1/2a study show that rFVIIIFc has an extended half-life, which may have the potential to provide extended protection from bleeding and reduce the number of infusions necessary for prophylactic treatment of severe hemophilia A.”

Currently, prophylactic treatment of severe hemophilia A requires intravenous infusions three times a week or every other day. rFVIIIFc is a fully-recombinant and fully-active clotting factor designed to replace the protein that hemophilia A patients lack and to last longer in the body than commercially-available factor VIII products. Developed using Biogen Idec’s proprietary Fc fusion technology, rFVIIIFc utilizes a natural pathway that recycles rFVIIIFc in the circulation to extend its half-life.

“Biogen Idec is driven to deliver innovative treatments that can make much-needed progress for people with hemophilia,” said Glenn Pierce, M.D., Ph.D., Senior Vice President of Hemophilia at Biogen Idec. “These study results demonstrate the potential of our Fc fusion technology to develop long-lasting clotting factors that may significantly reduce the burden of treatment and improve quality of life for people with hemophilia.”

“These results are promising and supported the advancement of rFVIIIFc into a Phase 3 trial last year,” said Peter Edman, Ph.D., Chief Scientific Officer of Swedish Orphan Biovitrum. “We are excited about the potential of rFVIIIFc to make a positive impact on the health and quality of life of hemophilia A patients by providing extended protection from bleeding.”

rFVIIIFc is currently being studied in a registrational, open-label, multicenter trial (A-LONG), which is evaluating its safety, pharmacokinetics and efficacy in the prevention and treatment of bleeding in previously-treated patients with severe hemophilia A.

Additionally, the European Medicines Agency’s (EMA) Pediatric Committee recently adopted an opinion agreeing to the pediatric investigational plan for rFVIIIFc. In accordance with the opinion, Biogen Idec and Swedish Orphan Biovitrum plan to initiate a global pediatric trial in previously-treated patients under 12 years of age as soon as sufficient data are available from a study of older patients. Under draft guidelines published by the EMA for the development of factor VIII products, pediatric data from this trial will be required in the initial submission of a Marketing Authorization Application to the European regulatory agency.

About the Phase 1/2a Study

The Phase 1/2a open-label, cross-over, multi-center, dose-escalation study evaluated the safety and pharmacokinetics of an intravenous injection of rFVIIIFc in 16 previously-treated patients with severe hemophilia A. The primary objective of the study was to assess the safety of rFVIIIFc at different doses; the secondary objective was to estimate the pharmacokinetic parameters of rFVIIIFc at doses ranging from 25 to 65 IU/kg.

rFVIIIFc was well tolerated in this single-dose study, with no drug-related serious adverse events. Adverse events were observed in 11 out of 16 patients, with one related to study drug – dysguesia (abnormal taste in the mouth). There were no signs of injection site reactions, inhibitor development or anti-rFVIIIFc drug antibodies.

rFVIIIFc demonstrated an approximately 1.7-fold increase in half-life compared to Advate. Other PK parameters such as mean residence time and area under the curve (AUC) were similarly increased. Furthermore, peak plasma concentration and AUC also demonstrated an increase proportional to the dose administered relative to Advate. Advate and rFVIIIFc had comparable and dose-dependent peak plasma concentration, and comparable recovery.

About Fc Fusion Technology and the Long-Lasting Recombinant Hemophilia Program

Developed using Biogen Idec’s proprietary Fc fusion technology, rFVIIIFc utilizes a natural pathway that recycles rFVIIIFc in the circulation to extend its half-life and allow factor to remain in the body longer after an infusion.

Using the same, natural Fc fusion technology as rFVIIIFc, Biogen Idec and Swedish Orphan Biovitrum are also developing a fully-recombinant, long-lasting Factor IX Fc fusion protein (rFIXFc) for the treatment of hemophilia B. rFIXFc is currently being tested in a registrational, open-label, multicenter trial (B-LONG), which is designed to evaluate its safety, pharmacokinetics and efficacy in prevention and treatment of bleeding in hemophilia B patients. For more information on the rFVIIIFc and rFIXFc trials, please visit www.biogenidechemophilia.com or www.clinicaltrials.gov.

About Hemophilia A

Hemophilia A is a rare, inherited disorder in which the ability of a person’s blood to clot is impaired. Hemophilia A occurs in about one in 5,000 male births annually and is caused by having substantially reduced or no factor VIII protein, which is needed for normal blood clotting. People with hemophilia A therefore need injections of factor VIII to restore the coagulation process and prevent frequent bleeds that could otherwise lead to pain, irreversible joint damage and life-threatening hemorrhages. Prophylactic treatment with infusions three times per week or every other day to maintain a sufficient circulating level of coagulation factor is being increasingly used, and long-term studies demonstrate that such regimens increase the patient’s life expectancy and greatly reduce, if not eliminate, progressive joint deterioration.

About Biogen Idec

Biogen Idec uses cutting-edge science to discover, develop, manufacture and market therapies for serious diseases with a focus on neurology, immunology and hemophilia. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $4 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Swedish Orphan Biovitrum (Sobi)

Sobi is a leading European specialty pharmaceutical company focused on providing and developing specialty pharmaceuticals for patients with rare diseases and significant medical needs. The portfolio comprises about 60 marketed products, as well as projects in late clinical phase. Key therapeutic areas are hematological diseases, autoimmune diseases, hereditary metabolic disorders and therapeutic oncology. In 2010 Sobi had revenues of SEK 1.9 billion and approximately 500 employees. The share (STO: SOBI) is listed on NASDAQ OMX Stockholm. For more information please visit www.sobi.com.

Safe Harbor

This press release contains forward-looking statements, including statements about the development and potential effects of long-lasting hemophilia therapies. These statements may be identified by words such as “believe,” “expect,” “may,” “plan,” “will” and similar expressions, and are based on the companies’ current beliefs and expectations. Drug development and commercialization involve a high degree of risk. Factors which could cause actual results to differ materially from the companies’ current expectations include the risk that we may not fully enroll our planned clinical trials, unexpected concerns may arise from additional data or analysis, regulatory authorities may require additional information, further studies, or may fail to approve our drug candidates, or the companies may encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with Biogen Idec’s drug development and commercialization activities, please review the Risk Factors section of Biogen Idec’s most recent annual or quarterly report filed with the Securities and Exchange Commission. Any forward-looking statements speak only as of the date of this press release and the companies assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Swedish Orphan Biovitrum may be required to disclose the information provided herein pursuant to the Swedish Securities Markets Act. The information was provided for public release on July 26, 2011 at 6:30 a.m. CET.

SOURCE: Biogen Idec

MEDIA CONTACTS: 
Biogen Idec Tracy Vineis, +1 781-464-3260 
Senior Manager, Public Affairs 
or 
Swedish Orphan Biovitrum: 
Peter Edman, CSO, +46 8 629 21 77
peter.edman@sobi.com

Long_lasting Hemophilia B Therapy Opinion from EMA

Biogen Idec and Swedish Orphan Biovitrum Receive Opinion from EMA on Pediatric Plan for Long-Lasting Hemophilia B Therapy

WESTON, Mass. & STOCKHOLM, May 09, 2011 (BUSINESS WIRE) –
Biogen Idec (NASDAQ: BIIB) and Swedish Orphan Biovitrum (STO: SOBI) today announced that the European Medicines Agency’s (EMA) Pediatric Committee (PDCO) has adopted an opinion agreeing to the pediatric investigational plan for the companies’ long-lasting, fully-recombinant Factor IX Fc fusion protein (rFIXFc).

In accordance with the PDCO’s opinion, Biogen Idec and Swedish Orphan Biovitrum plan to initiate a global pediatric trial in previously-treated patients under 12 years of age as soon as sufficient data are available from a study of older patients. Under draft guidelines published by the EMA for the development of Factor IX products, pediatric data from this trial will be required in the initial submission of a Marketing Authorization Application to the European regulatory agency.

“The EMA’s agreement to our pediatric investigational plan is another milestone in our effort to develop innovative therapies for people with hemophilia,” said Glenn Pierce, M.D., Ph.D., Senior Vice President of Hemophilia at Biogen Idec. “With this opinion and the ongoing Phase 3 trials of our long-lasting Factor IX and Factor VIII programs, we continue to make progress toward our goal of improving the way hemophilia is treated worldwide.”

“The opinion from the EMA’s Pediatric Committee is valuable for our promising rFIXFc project, as it allows for the development of rFIXFc in the pediatric population. We are excited about the potential of this innovative product to make a difference in the lives of people with hemophilia,” said Peter Edman, Ph.D., Chief Scientific Officer of Swedish Orphan Biovitrum.

About rFIXFc and the recombinant Fc Fusion protein hemophilia program

rFIXFc is a recombinant Factor IX Fc fusion protein developed using monomeric Fc fusion technology. The technology makes use of a natural mechanism that recycles rFIXFc in the circulation to extend its half-life. It is a fully-recombinant clotting factor designed to replace the protein that hemophilia B patients lack and to last longer in the body than commercially-available Factor IX products. rFIXFc is currently being evaluated in a registrational, open-label, multicenter trial (B-LONG) designed to evaluate its safety, pharmacokinetics and efficacy in hemophilia B patients.

Using the same proprietary monomeric Fc fusion technology as rFIXFc, Biogen Idec and Swedish Orphan Biovitrum are also developing a fully-recombinant, long-lasting Factor VIII Fc fusion protein (rFVIIIFc) for the treatment of hemophilia A. rFVIIIFc is currently being evaluated in a registrational, open-label, multicenter trial (A-LONG) designed to evaluate its safety, pharmacokinetics and efficacy in hemophilia A patients. For more information on the rFIXFc and rFVIIIFc trials, please visit http://www.biogenidechemophilia.com/ or http://www.clinicaltrials.gov/.

About Hemophilia B

Hemophilia B is a rare, inherited disorder in which the ability of a person’s blood to clot is impaired. Hemophilia B occurs in about one in 25,000 male births annually and is caused by having substantially reduced or no Factor IX protein, which is needed for normal blood clotting. People with hemophilia B therefore need injections of Factor IX to restore the coagulation process and prevent frequent bleeds that could otherwise lead to pain, irreversible joint damage and life-threatening hemorrhages. Prophylactic treatment with infusions twice per week to maintain a sufficient circulating level of coagulation factor is being increasingly used, and long-term studies demonstrate that such regimens increase the patient’s life expectancy and greatly reduce, if not eliminate, progressive joint deterioration.

About Biogen Idec

Biogen Idec uses cutting-edge science to discover, develop, manufacture and market therapies for serious diseases with a focus on neurology, immunology and hemophilia. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $4 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Swedish Orphan Biovitrum (Sobi)

Sobi is a Swedish-based niche specialty pharmaceutical company with an international market presence. The company is focused on providing and developing specialist pharmaceuticals for rare disease patients with high medical needs. The portfolio consists of about 60 marketed products and an emerging late-stage clinical development pipeline. Our focus areas are: hemophilia, inflammation/autoimmune diseases, fat malabsorption, cancer and inherited metabolic disorders. Sobi had pro-forma revenues 2009e of about 2 BSEK and approximately 500 employees. The head office is located in Sweden and the share (STO: SOBI) is listed on NASDAQ OMX Stockholm..

Safe Harbor

This press release contains forward-looking statements, including statements about the development of long-lasting hemophilia therapies. These statements may be identified by words such as “believe,” “expect,” “may,” “plan,” “will” and similar expressions, and are based on the companies’ current beliefs and expectation. Drug development involves a high degree of risk. Factors which could cause actual results to differ materially from the companies’ current expectations include the risk that we may not fully enroll our planned clinical trials, unexpected concerns may arise from additional data or analysis, regulatory authorities may require additional information, further studies, or may fail to approve the drug, or the companies may encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with Biogen Idec’s drug development and other activities, see the periodic reports of Biogen Idec filed with the Securities and Exchange Commission. Any forward-looking statements speak only as of the date of this press release and the companies assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Swedish Orphan Biovitrum may be required to disclose the information provided herein pursuant to the Swedish Securities Markets Act. The information was provided for public release on May 9, 2011, 11:00 a.m. CET.

First Long-Lasting Factor VIII Candidate in Late-Stage Clinical Trial for Treatment of Hemophilia A

Biogen Idec and Swedish Orphan Biovitrum Announce First Patient Dosed in Global Registrational Trial of Long-Lasting Recombinant Factor VIII Fc Fusion Protein

WESTON, Mass. & STOCKHOLM, Dec 06, 2010 (BUSINESS WIRE) –

Biogen Idec (NASDAQ: BIIB) and Swedish Orphan Biovitrum (STO: SOBI) today announced that the first patient has been dosed with the companies’ long-lasting recombinant Factor VIII Fc fusion protein (rFVIIIFc) in a global registrational clinical trial. The study, called A-LONG, is an open-label, multicenter, Phase 2/3 study designed to evaluate the safety, pharmacokinetics and efficacy of rFVIIIFc in previously-treated hemophilia A patients.

“Treatment of hemophilia A involves frequent injections that can often be a major burden for individuals with the disorder, as well as their families,” said John Pasi, M.D., Co-Principal Investigator of the A-LONG trial and Professor of Haemostasis and Thrombosis, Barts and The London School of Medicine and Dentistry, London. “There is a significant unmet need for a Factor VIII product, like rFVIIIFc, with the potential to prolong protection from bleeding and yet reduce the frequency of infusions, as well as potentially reduce the complications of hemophilia and improve the quality of life for these patients.”

rFVIIIFc is a fully-recombinant clotting factor developed using Biogen Idec’s novel and proprietary monomeric Fc fusion technology. The A-LONG trial is designed to evaluate different dosing regimens of rFVIIIFc in the prevention of bleeding as measured by the number of breakthrough bleeding episodes over the study period. The study will also evaluate the efficacy of rFVIIIFc in on-demand and surgical settings, and compare the pharmacokinetics of a single dose of rFVIIIFc with a single dose of a commercially-available recombinant Factor VIII product (Advate,^(R) antihemophilic factor recombinant, plasma/albumin-free method, rFVIII).

“Dosing the first patient in the A-LONG study is an important milestone in our progress toward developing a treatment that has the potential to make a difference for the hemophilia A community,” said Glenn Pierce, M.D., Ph.D., Vice President and Chief Medical Officer of Biogen Idec’s hemophilia therapeutic area. “This trial, along with the ongoing Phase 2/3 study of our fully-recombinant, long-lasting Factor IX Fc fusion protein for the treatment of hemophilia B, further demonstrates our strong commitment to developing better treatments for the worldwide hemophilia community.”

“rFVIIIFc is an innovative therapy that offers the potential to make a positive impact in the lives of people with hemophilia A,” said Peter Edman, Ph.D., Chief Scientific Officer of Swedish Orphan Biovitrum. “The initiation of this trial builds on the positive data that we saw in our Phase 1/2a study, and it is also an exciting achievement for Swedish Orphan Biovitrum.”

About The A-LONG Study

A-LONG is an open-label, multicenter clinical trial designed to evaluate the safety, pharmacokinetics and efficacy of rFVIIIFc in the prevention and treatment of bleeding in previously-treated patients with severe hemophilia A. The trial is expected to enroll approximately 150 patients in 60 centers globally. The study will include male patients aged 12 years and above who have a diagnosis of severe hemophilia A, a history of at least 150 documented prior exposure days to any currently-marketed Factor VIII product and a platelet count of greater-than or equal to 100,000 cells/L. Patients will be assigned into three arms: high-dose prophylaxis, low-dose prophylaxis and on-demand.

The study’s objectives are to evaluate the safety and tolerability of rFVIIIFc, which will be measured by evaluating clinically notable changes from baseline in physical examinations, vital signs, lab values, and incidence of adverse events and inhibitor development. The study will also assess the potential of rFVIIIFc to enable protection from bleeding by evaluating the number of both spontaneous and traumatic bleeding episodes in each treatment arm. The A-LONG trial will evaluate different dosing regimens of rFVIIIFc in the prevention of bleeding. Secondary endpoints include total rFVIIIFc consumption per subject, response to treatment and the pharmacokinetics of a single dose of rFVIIIFc versus Advate.

About rFVIIIFc And The Recombinant Fc-Fusion Protein Hemophilia Program

rFVIIIFc is a recombinant Factor VIII Fc fusion protein developed using monomeric Fc fusion technology. The technology makes use of a natural mechanism that recycles rFVIIIFc in the circulation to extend its half-life. It is a fully-recombinant clotting factor designed to replace the protein that hemophilia A patients lack and to last longer in the body than commercially-available Factor VIII products.

The decision to progress rFVIIIFc into a registrational trial was based on strong Phase 1/2a clinical data and supportive preclinical data. In July, Biogen Idec and Swedish Orphan Biovitrum announced data from the Phase 1/2a open-label, dose-escalation study that evaluated the safety and pharmacokinetics of an intravenous injection of rFVIIIFc in 16 previously-treated patients with severe hemophilia A. In the study, rFVIIIFc demonstrated a prolonged half-life compared to Advate and was well tolerated with no drug related serious adverse events. Adverse events were observed in 11 out of 16 patients, with only one related to study drug – dysguesia (abnormal taste in the mouth).

Using the same proprietary monomeric Fc fusion technology as rFVIIIFc, Biogen Idec and Swedish Orphan Biovitrum are also developing a fully-recombinant, long-lasting Factor IX Fc fusion protein (rFIXFc) for the treatment of hemophilia B. rFIXFc is currently being evaluated in a registrational, open-label, multicenter trial (B-LONG) designed to evaluate its safety, pharmacokinetics and efficacy in hemophilia B patients. For more information on the rFIXFc and rFVIIIFc trials, please visit www.biogenidechemophilia.com or www.clinicaltrials.gov.

About Hemophilia A

Hemophilia A is a rare, inherited disorder in which the ability of a person’s blood to clot is impaired. Hemophilia A occurs in about one in 5,000 male births annually and is caused by having substantially reduced or no Factor VIII protein, which is needed for normal blood clotting. People with hemophilia A therefore need injections of Factor VIII to restore the coagulation process and prevent frequent bleeds that could otherwise lead to pain, irreversible joint damage and life-threatening hemorrhages. Prophylaxis treatment with infusions three times per week or every other day to maintain a sufficient circulating level of coagulation factor is being increasingly used, and long-term studies demonstrate that such regimens increase the patient’s life expectancy and greatly reduce, if not eliminate, progressive joint deterioration.

About Biogen Idec

Biogen Idec uses cutting-edge science to discover, develop, manufacture and market biological products for the treatment of serious diseases with a focus on neurological disorders. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $4 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Swedish Orphan Biovitrum

Swedish Orphan Biovitrum is a Swedish-based niche specialty pharmaceutical company with an international market presence. The company is focused on providing and developing specialist pharmaceuticals for rare disease patients with high medical needs. The portfolio consists of about 60 marketed products and an emerging late-stage clinical development pipeline. Our focus areas are: hemophilia, inflammation/autoimmune diseases, fat malabsorption, cancer and inherited metabolic disorders.

Swedish Orphan Biovitrum had pro-forma revenues 2009e of about 2 BSEK and approximately 500 employees. The head office is located in Sweden and the share (STO: SOBI) is listed on NASDAQ OMX Stockholm. For more information please visitwww.sobi.com.

Safe Harbor

This press release contains forward-looking statements regarding the development of long-lasting hemophilia therapies, which may be identified by words such as “believe,” “expect,” “may,” “plan,” “will” and similar expressions. These statements are based on the companies’ current beliefs and expectation. Drug development involves a high degree of risk. Factors which could cause actual results to differ materially from the companies’ current expectations include the risk that we may not fully enroll our planned clinical trials, unexpected concerns may arise from additional data or analysis, regulatory authorities may require additional information, further studies, or may fail to approve the drug, or the companies may encounter other unexpected hurdles. For more detailed information on the risks and uncertainties associated with Biogen Idec’s drug development and other activities, see the periodic reports of Biogen Idec filed with the Securities and Exchange Commission. Any forward-looking statements speak only as of the date of this press release and the companies assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Swedish Orphan Biovitrum may be required to disclose the information provided herein pursuant to the Swedish Securities Markets Act. The information was provided for public release on Dec 6, 2010 at 8:30 a.m. CET.

Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=6534255&lang=en

SOURCE: Biogen Idec

Biogen Idec Media:
Kate Weiss, +1-781-464-3260
Manager, Public Affairs
or
Biogen Idec Investor Relations:
Kia Khaleghpour, +1-781-464-2442
Associate Director, Investor Relations
or
Swedish Orphan Biovitrum:
Peter Edman, CSO, +46 8 629 21 77
peter.edman@sobi.com
or
Swedish Orphan Biovitrum:
Erik Kinnman, +46 73 422 15 40
Vice President, Investor Relations and Public Affairs
erik.kinnman@sobi.com

Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Subjects With Hemophilia B

Purpose:

The study is to investigate the safety, pharmacokinetics (the determination of the concentration of the administered drug in blood over time), and efficacy (length of effect and duration of circulating) of recombinant Factor IX Fc fusion protein (rFIXFc) in previously-treated subjects with hemophilia B.

Still recruiting in:

Arkansas
Washington D.C.
Indiana
Pennsylvania
Washington
Sweden
United Kingdom

To see the Clinical Trial Info click here. 

To see the Press Release click here.

ClinicalTrials.gov identifier: NCT01027364

Longer Acting Recombinant Factor IX

Recombinant Factor IX Monomer Formulation Yields Good Results in Patients With Severe Haemophilia B: Presented at Hemophilia 2010

By Thomas R. Collins
From DOC Guide 

BUENOS AIRES — July 13, 2010 — In the first human trial of rFIX-Fc using monomer technology — a recombinant molecular fusion of coagulation factor IX (FIX) and the Fc region of immunoglobulin G– the treatment was found to perform well in patients with severe haemophilia B and had an encouraging safety profile, researchers said here at the Hemophilia 2010 World Congress.The treatment had a 3-fold increase in half-life and mean residence time compared with an established therapy (BeneFIX) along with a 24% improvement in incremental recovery.

Researchers said the findings are a sign that rFIX-Fc might not have to be treated as often.

“Monomer technology is being applied to FIX for treatment of haemophilia B,” said Amy Shapiro, MD, Indiana Hemophilia & Thrombosis Center, Indianapolis, Indiana, on July 11. “Monomer configuration has demonstrated a range of improvements for a variety of proteins.”

This trial, she said, showed that “activity of rFIX-Fc is preserved over time.”

Fourteen patients were enrolled at 7 haemophilia centres in the United States and Hong Kong. Subjects participated for 60 days, with 13 visits.

The half-life of rFIX-Fc averaged 52.5 hours, compared with historical data from another study that showed the half-life of BeneFIX averaged 19.3 hours.

The mean response time was 68 hours, which was also about 3 times longer than historical data for BeneFIX.

Incremental recovery was also improved with rFIX-Fc – 0.93 IU/dL per IU/kg compared with 0.75 IU/dL per IU/kg.

Six doses were tested in the study, ranging from 1 to 100 IU/kg.

Drug-related adverse events included an abnormal taste in the mouth and headache. There were no serious adverse events linked to the drug, Dr. Shapiro said.

Researchers found that the effects corresponded to dosage, with maximum thrombin concentrations rising evenly with the amount of the treatment administered.

Dr. Shapiro said the results give rise to new possibilities for treatment. “There are implications here both for this specific product as well as for all long-acting products for future development,” she said. “Specifically related to the recombinant IX-Fc protein, this data supports administration at less frequent intervals, perhaps once weekly, or at higher doses with even longer intervals, based upon specific patients.”

For all longer-acting products, she said, “Fewer injections, especially in a younger patient, lead to a decreased need for placement of a venous access device.”

Funding for this study was provided by Biogen Idec.

[Presentation title: Safety and Prolonged Biological Activity Following a Single Administration of a Recombinant Molecular Fusion of Native Human Coagulation Factor IX and the Fc Region of Immunoglobulin G (IgG)(rFIXFc) to Subjects With Hemophilia B]

Biovitrum Advances Novel Factor VIII Long-Acting Hemophilia A Therapy into Clinical Trials

Stockholm, Sweden – Dec 15, 2009 – Biovitrum AB (publ) (STO: BVT) today announced that the first patient was dosed in a phase I/IIa study of its long-acting fully-recombinant Factor VIII Fc fusion (rFVIIIFc) protein. The phase I/IIa open-label study will assess the safety, tolerability and pharmacokinetics of rFVIIIFc in severe, previously-treated, hemophilia A patients. The rFVIIIFc program and international study are partnered with Biogen Idec (NASDAQ: BIIB).

  

Hemophilia A patients require frequent Factor VIII injections, which create a significant burden for these individuals. The rFVIIIFc molecule is being investigated for the potential to prolong protection from bleeding and reduce the frequency of injections for both prophylaxis and on-demand therapy in Hemophilia A. Preclinical studies showed improved half-life of rFVIIIFc, which is based on Biogen Idec’s monomeric Fc-fusion technology (recently presented 7 December 2009 at the American Society of Hematology conference). 

 

“We are excited about bringing rFVIIIFc into the clinical stage together with Biogen Idec and, thereby adding another significant collaboration project to the ongoing recombinant Factor IX Fc fusion (rFIXFc)  clinical program. The innovative rFVIIIFc program holds great potential in offering true value to hemophilia A patients, and is thus a prioritized therapeutic and business area within Biovitrum,” said Peter Edman, CSO of Biovitrum.

 

About Hemophilia A

Hemophilia A is a rare, inherited disorder in which the ability of a person’s blood to clot is impaired. Hemophilia A occurs in about 1 in 10,000 male births annually and is caused by having substantially reduced or no factor VIII protein, which is needed for normal blood clotting. People with hemophilia A therefore need injections of factor VIII to restore the coagulation process and prevent frequent bleeds that could otherwise lead to pain, irreversible joint damage and life-threatening hemorrhages. Prophylaxis treatment with infusions three times per week or every second day to maintain a sufficient circulating level of coagulation factor is being increasingly used, and long-term studies demonstrate that such regimens increase the patient’s life expectancy and greatly reduce if not eliminate progressive joint deterioration. The current global market for recombinant Factor VIII products is over 4 BUSD annually.

 

About Biovitrum

Biovitrum is an international pharmaceutical company that markets specialist pharmaceuticals in several regions. Using its expertise and experience Biovitrum takes scientific innovation to patients with significant unmet medical need. Research expertise and capabilities are focused on development and production of biotechnology therapeutics within our prioritized areas of hemophilia, inflammation/autoimmune diseases, cancer supportive care and malabsorption. The company has revenues of approximately SEK 1.2 billion and around 400 employees. The company head office is located in Sweden and it is listed on the Stockholm OMX Nordic Exchange. For more information please visit www.biovitrum.com.

 

 

 

 

For more information please contact:

 

Biovitrum AB (publ)

Erik Kinnman, EVP Investor Relations

Phone: +46 73 422 15 40

erik.kinnman@biovitrum.com

 

 

Peter Edman, CSO

Phone: +46 8 697 21 77

 

 

Biovitrum AB (publ) may be required to disclose the information provided herein pursuant to the Swedish Securities Markets Act. The information was provided for public release on December 15, 2009 at 08:30 a.m. CET.

for the Pdf of this this press release click here.