Ipsen’s Partner Inspiration Biopharmaceuticals Announces Non-Inferiority Of IB1001, Its Recombinant Factor IX For Hemophilia B

Ipsen (Paris:IPN) (Euronext: IPN, ADR: IPSEY) announced that its partner Inspiration Biopharmaceuticals, Inc. (Inspiration) presented pharmacokinetic (PK) data on its lead product, IB1001, a recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with hemophilia B. According to Inspiration, results of the Phase 1 portion of an ongoing IB1001 clinical study demonstrated non-inferiority of IB1001 in achieving overall levels of replacement factor compared to BeneFIX®, the only approved recombinant FIX product for the treatment of hemophilia B. Currently, IB1001 is in Phase 3 and safety and efficacy results are expected later this year. 

The clinical results were presented at the 4th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) in Geneva, Switzerland, in a poster presentation titled, “Pharmacokinetics of IB1001, a New Recombinant Factor IX”1.

Marc de Garidel, Chairman and Chief Executive Officer of Ipsen said:
“Pharmacokinetic results presented by our partner Inspiration Biopharmaceuticals emphasize the encouraging medical potential of IB1001, a promising factor IX for the treatment of hemophilia B, a disease for which access to adequate care is a significant unmet medical need globally.”

About the study
The randomized, double-blind, cross-over PK protocol was designed to show non-inferiority of IB1001 compared to the only marketed recombinant FIX product. The study enrolled 32 individuals with severe hemophilia B. Individuals in the study were infused with either IB1001 or the comparator, and their FIX levels were assessed at different time intervals. After a predetermined time period, individuals received the second product and FIX levels were assessed at the same time points.

Inspiration is continuing to recruit patients for the Phase 3 portion of the Company’s IB1001 study, including for the treatment of patients undergoing major surgical procedures. For more information on the ongoing study, please visit http://www.clinicaltrials.gov/ct2/show/NCT00768287.

About Hemophilia

Hemophilia is a bleeding disorder caused by low levels or absence of a protein called a coagulation factor, essential for blood clotting. The two most common forms of hemophilia are types A and B. Hemophilia A is caused by a factor VIII deficiency and the congenital form occurs in ~1 out of every 5,000 male births. Hemophilia B is caused by factor IX deficiency and occurs in ~1 out of every 30,000 male births. Approximately 60% of persons with hemophilia have a severe condition, which results in frequent spontaneous bleeding episodes, in addition to serious bleeding after injuries. The annual market for hemophilia treatments is $7.5 billion worldwide.

About IB1001

IB1001, Inspiration’s lead product candidate, is an intravenous recombinant FIX product being developed for the treatment and prevention of bleeding in individuals with hemophilia B. IB1001 currently is in pivotal Phase 3 clinical testing. To date, IB1001 has been well-tolerated, and pharmacokinetic results have demonstrated non-inferiority to the one approved recombinant FIX product for the treatment of hemophilia B. Pending results from clinical studies, regulatory approval and commercialization, IB1001 is expected to be the second recombinant FIX product to market, and thereby to increase product supply and access to care worldwide.

The Group also depends on third parties to develop and market some of its products which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to the Group’s activities and financial results.

The Group expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. The Group’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers.

1 Authors of the poster presentation were Uri Martinowitz, M.D., of the Israeli National Hemophilia Center; Amy D. Shapiro, M.D., of the Indiana Hemophilia and Thrombosis Center; Doris V. Quon, M.D., Ph.D., of the Hemophilia Treatment Center at Orthopaedic Hospital (Los Angeles, CA); Miguel A. Escobar, M.D., of the University of Texas Houston Health Sciences Center; Christine Kempton, M.D., of Emory University School of Medicine (Atlanta, GA); Peter W. Collins, M.D., of the Arthur Bloom Haemophilia Centre University Hospital of Wales School of Medicine, Cardiff University (Cardiff, UK); Pratima Chowdary, M.D., of the Royal Free Hospital (London, UK); Michael Makris, M.D., of the Royal Hallamshire Hospital (Sheffield, UK); Pier M. Mannucci, M.D., of the University of Milan Haemophilia & Thrombosis Center; Massimo Morfini, M.D., of Azienda Ospedaliero – Universitaria Careggi (Florence, Italy); Leonard A. Valentino, M.D., of Rush University Medical Center (Chicago, IL); and Ed Gomperts, M.D., and Martin Lee, Ph.D., both of Inspiration Biopharmaceuticals.

Natural molecule indirectly prevents stable clot formation

ScienceDaily (Feb. 2, 2011) — A scientist from The Scripps Research Institute has identified a new role for a natural signaling molecule in preventing blood clot formation. The molecule could become a target for the development of novel and cost-effective treatments for blood clotting diseases such as Hemophilia A.

The findings, from a study by Scripps Research Assistant Professor Laurent O. Mosnier, were published in a recent edition of Journal of Biological Chemistry.

The study focused on Platelet Factor 4 — a small cytokine (intracellular signaling molecule) released during platelet aggregation.

Based on Platelet Factor 4 effects on another coagulation protein, it was thought that Platelet Factor 4 could potentially stimulate activation of thrombin-activatable fibrinolysis inhibitor (TAFI) — an enzyme (soluble protein) that protects clot longevity, making clots last longer and preventing excess bleeding; TAFI is like a hardener that is added to the mortar used between the bricks in a brick wall, without which the mortar would never completely solidify, and the wall would never be solid.

The new study, however, found exactly the opposite role for Platelet Factor 4 — inhibition of TAFI activation.

For Mosnier, this finding led to a radical idea — sequestering Platelet Factor 4 using such molecules as heparin derivatives could improve clot stability. Heparin — a highly sulfated or negatively charged glucoseaminoglycan (polysaccharide or sugar derivative) — is a commonly used anticoagulant. Mosnier, however, was able to modify the compound to have the reverse effect and aid in blood clotting in laboratory tests.

“The idea of using heparin to prevent bleeding in kids [who have bleeding tendencies] would be outrageous because that would just greatly accelerate bleeding,” said Mosnier, “Our trick, however, was to modulate heparin’s anticoagulant properties. This opens up new possibilities.”

Converting Heparin from an Anticoagulant into a Non-Anticoagulant

Heparin’s anticoagulant activity is derived from a specific pattern of nitrogen- and oxygen-linked sulfation (or simply negative charges) that is recognized by anti-thrombin — the inactivator of coagulation. However, in addition to binding to anti-thrombin heparin also binds to Platelet Factor 4, which is glittered with positive charge, and they attract one another like magnets.

Mosnier found heparin’s anticoagulant activity could be prevented, and its Platelet Factor 4 binding selected for, by selectively removing the N-linked sulfations (and further acetylation). This effectively prevented heparin from being recognized by anti-thrombin and allowed it to instead take the Platelet Factor 4 out of the equation. This resulted in prevention of clot breakdown (fibrinolysis), by allowing TAFI to do its job.

To test the effectiveness of the modified heparin derivatives in enhancing clot stability, Mosnier employed a functional assay called a “clot lysis assay.” Using a light scattering technique, plasma was used to generate a clot, which was degraded. Further modulation of the conditions allowed measurement of clot stability via TAFI activation. Mosnier found that, indeed, the modified-version heparin promoted clot stability.

Toward a Cheaper, Cost-Effective Treatment for Hemophilia A

An optimistic Mosnier admits his new discovery is in its infancy, but hopes it may one day provide an alternative treatment for bleeding conditions such as Hemophilia A.

Hemophilia A, which affects 1 in 5,000 males, is an X-linked genetic bleeding disorder whereby there is a reduced amount or activity of factor VIII. This results in the unstable clots, lacking fibrin — a fibrous clot-forming protein. Currently, the treatment for Hemophilia A is prophylactically taking factor VIII as a medicine to improve clotting. Unfortunately, immunity against factor VIII is a significant side effect.

Mosnier hopes that modification of heparin — which is cheaper than factor VIII and already used clinically — could one day stabilize clots in these patients.

“The next step is to see if the modified compound will improve bleeding complications in the Hemophilia mouse,” said Mosnier. “We are still a long way from claiming anything clinically.”

His optimism is contagious, however, and it is an exciting time for science in the Mosnier lab.

This research was funded by a “Pathway to Independence Grant,” which enabled the establishment of the Mosnier Lab, from the National Institute of Health (NHLBI Grant HL087618).

PROLOR BIOTECH ANNOUNCES POSITIVE PRECLINICAL RESULTS FROM LONG-ACTING FACTOR IX COMPARATIVE STUDY

 ––Factor IX-CTP May Provide Hemophilia Patients Prolonged Protection from Bleeding and Enable Reduction in Number of Required Injections to Once-Weekly or Less––  

 Nes-Ziona, Israel – February 2, 2011 

– PROLOR Biotech, Inc., (NYSE Amex: PBTH), today reported positive results from a comparative study of its biobetter longer-acting version of the hemophilia drug Factor IX (Factor IX-CTP) in Factor IX-depleted hemophilic mice. The study was designed to measure the potential increase in clotting activity and duration of therapeutic effect of PROLOR’s long-acting CTP-modified Factor IX when compared with commercially available recombinant Factor IX. Factor IX is indicated for the treatment of acute bleeding episodes and as therapy for prevention of bleeding in hemophilia B patients.In the study, Factor IX-CTP, when compared with commercially available Factor IX, demonstrated a significantly longer duration of clotting activity in the hemophilic mice model. Bleeding episodes were also significantly shorter and less intense for the group treated with Factor IX-CTP. In addition, none of the animals treated with Factor IX-CTP had any spontaneous re-bleeding events, compared with a 50% incidence of re-bleeding events for the group treated with commercial Factor IX and an 83% incidence of re-bleeding events for the untreated group.

The new study results support previous preclinical studies that demonstrated significant improvements in the half-life of Factor IX-CTP compared to commercially available Factor IX.

“We believe that this study further validates CTP as a leading platform for developing long-acting therapeutic proteins, demonstrating that the fundamental ability of CTP to extend duration of therapeutic effect while increasing biological activity is consistent across various types of proteins,” noted Shai Novik, President of PROLOR. “The utility of CTP has previously been validated for non-enzyme proteins, such as Merck’s hormone therapy Elonva® and PROLOR’s human growth hormone, interferon beta and erythropoietin. With this successful Factor IX study, we have now additionally confirmed the applicability of CTP technology for the development of biobetter enzymes.”

“We believe there is great need among hemophilia patients and their physicians for therapies that will provide prolonged protection from bleeding,” said Dr. Abraham Havron, CEO of PROLOR. “The encouraging efficacy seen in our preclinical hemophilia study, together with the impressive half-life extension seen in our previous studies, show that Factor IX-CTP may be able to reduce the number of injections needed by hemophilia B patients to once-weekly or less.”

Dr. Havron added, “We believe that these results further confirm the clinical potential of Factor IX-CTP to become an important long-acting therapy for the treatment of acute bleeding episodes and for prevention of bleeding in hemophilia B patients. We are moving forward with our plan to initiate our first clinical study of Factor IX-CTP in hemophilia in early 2012.”

 

About Hemophilia and Hemophilia B 

Hemophilia is a group of hereditary genetic disorders that impair the body’s ability to control blood clotting or coagulation. People with hemophilia do not produce adequate amounts of Factor VIII or Factor IX protein, which are necessary for effective blood clotting. In severe hemophiliacs even a minor injury can result in blood loss lasting days or weeks, and complete healing may not occur, leading to the potential for debilitating permanent damage to joints and other organs and premature death. According to the World Health Organization, more than 400,000 people have hemophilia, corresponding to an incidence of 15 to 20 in every 100,000 males born worldwide. Hemophilia B is associated with inadequate Factor IX and occurs at an incidence of about 1 in 20,000–34,000 male births. Hemophilia B is largely an inherited disorder but in approximately 30% of cases, there is no family history and the condition is the result of a spontaneous gene mutation. The availability of recombinant Factor VIII and Factor IX has enabled many hemophiliacs to live near-normal lives, but frequent injections are required.

 

ABOUT PROLOR BIOTECH PROLOR Biotech, Inc. is a clinical stage biopharmaceutical company applying unique technologies, including its patented CTP technology, primarily to develop longer-acting, proprietary versions of already approved therapeutic proteins that currently generate billions of dollars in annual global sales. The CTP technology is applicable to virtually all proteins, and PROLOR is currently developing long-acting versions of human growth hormone, which is in Phase II clinical development, and Factor VII, Factor IX, interferon beta and erythropoietin, which are in preclinical development, as well as an anti-obesity peptide and agents for atherosclerosis and rheumatoid arthritis. For more information, visit www.prolor-biotech.com

Complete article here.

 

FDA approved Corifact to treat congenital Factor XIII

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

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

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

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

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

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

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

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

Corifact is manufactured by CSL Behring of Marburg, Germany.

For more information: visit CSL Behring’s website.

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

Research improves diagnosis and treatment of bleeding disorder

From: Physorg.com

February 16, 2011
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–>A rare bleeding disorder that can lead to life-threatening bleeding episodes is misdiagnosed in 15 per cent of cases according to findings from a new international research project led by a Queen’s professor.

“Correct diagnosis is critical because it determines the treatment decision,” says Maha Othman, a professor in the Department of Anatomy and Cell Biology who led the three-year research project on the rare platelet type of von Willebrand disease (VWD).

Patients with VWD are commonly treated with drugs that help control their condition. However, these drugs aggravate bleeding in patients with the rarer platelet form of the disease, and misdiagnosis can leave these patients vulnerable to severe life-threatening bleeding episodes in situations like pregnancy and surgical operations.

Although both forms of VWD are genetic disorders that share many diagnostic features, the defect actually lies in two different genes. A correct diagnosis can only be made by closely examining certain areas of both genes to determine where the defect lies.

Dr. Othman’s study is the first large study to investigate the occurrence of the two types of VWD worldwide and to evaluate DNA analysis as a diagnostic tool.

In addition to pioneering this international project, Dr. Othman has also created an online registry aimed at determining the frequency of the rare platelet form of VWD and to collect data about the disorder. Despite its relative rarity, VWD is actually the most common genetically inherited bleeding disorder, affecting about one per cent of the general population.

Dr. Othman’s research will be published in the March issue of the Thrombosis and Haemostasis Journal.

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

From:  Haemophilia

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

Article first published online: 7 FEB 2011

DOI: 10.1111/j.1365-2516.2010.02450.x

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

CDC Guide Available for Hemophilia Healthcare Providers

The National Hemophilia Foundation is making available a self-learning guide for hemophilia healthcare providers. Foundations: A Comprehensive Approach to Hemophilia Care was developed and published in 2009 by the Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities and the Centers for Disease Control and Prevention (CDC). The booklet is a 2^nd edition; it was first published in 1996.

Foundations was created to enhance the knowledge base and skills of new healthcare providers to patients with hemophilia. When combined with continuing education and clinical practice, it is expected to improve hemophilia patient care. The booklet includes four education modules: “Introduction to Hemophilia”; “Bleeding Episodes”; “Complications of Hemophilia”; and “Psychosocial Implications of Hemophilia.”

The guide was developed in partnership with the CDC Foundation, through a grant from Baxter Healthcare Corporation.

To obtain a single copy of Foundations: A Comprehensive Approach to Hemophilia Care healthcare providers should contact HANDI, NHF’s information resource center: 800.424.2634 or handi@hemophilia.org.

Bill aims to stop specialty tier prescription drug costs

From: Carolyn Johnson, ABC7 San Francisco, CA 

Follow the above link for a video or click here.

SAN FRANCISCO (KGO) — There’s a new trend in health insurance to pass along the costs of the highest price medications to patients. Instead of a co-pay, patients are finding expensive drugs for cancer, arthritis and multiple sclerosis can cost them hundreds, even thousands of dollars out of pocket each month, but a Bay Area lawmaker is working to change that.

 

“My neurologist said, ‘You need to let your insurance company know that every day that goes by that you don’t take this drug, they are costing you neurological function,'” said MS patient Melanie Rowen.

That drug Rowen needed to manage her MS cost her nearly $700 a month. Her insurance classified it as a specialty tier drug, also known as Tier 4. That means she pays 30 percent of the cost of the drug rather than a simple co-pay.

When asked how she made it work financially, Rowen said, “I went into credit card debt.”

“What we’re hearing is things such as, ‘What do I do? Do I pay my mortgage?’ or ‘Do I go into debt?’ which is a common thing, people are going into debt or they’re going without some of the essentials of life,” said Stewart Ferry, the public policy director for the National MS Society.

Of the 12 most common Tier 4 drugs, four are used to treat MS.

“They’re just so frustrated because they’re paying their premiums and this runs completely counter to what insurance is supposed to be about, which is equitably spreading the risk. So this is antithetical to the very nature of insurance,” said Ferry.

Specialty tier pricing started under Medicare Part D. Michelle Vogel is executive director of the Alliance for Plasma Therapies and has been tracking the impact.

“Whatever happens with Medicare typically follows in private insurance, so when I was looking at the private plans, and especially in California, you’re seeing the majority of plans have put in Tier 4 plans,” said Vogel.

There’s a wide range of illnesses and diseases impacted by this change: cancer, rheumatoid arthritis, even hemophilia and organ transplantation.

“If you get a transplant, but the anti-rejection drug is too expensive to pay for, then why bother transplanting to begin with? You’ll die without that organ,” said Vogel.

“Sixty-one percent of Americans take some sort of prescription medication a day. So it is alarming when health plans are reclassifying drugs into a new Tier 4 category,” said Assm. Fiona Ma, D-San Francisco.

Ma is proposing legislation in California to prevent health insurers from moving vital medications to Tier 4 status.

“What we’re trying to do is make sure that patients are able to afford the medication they need. So we are going to look at a cap system as well as cost containment for the individuals who are on medication,” said Ma.

“What the cost is of a given drug starts with the manufacturer. We ought to look there and then both the health plan and the individual have roles to play in contributing to the cost of the drug,” said Patrick Johnston, CEO of the California Association of Health Plans.

Johnston is concerned about legislation that prevents cost sharing.

“If we have a drug co-pay that is tiered, then we can control the cost and make it more likely that more people can afford insurance,” said Johnston.

But a growing number of patients like Rowen are finding themselves facing a huge financial burden simply to get the drugs their doctors have prescribed.

“The stakes are high and nobody who has any choice about it is going to choose not to take them. It’s absolutely out of the question,” said Rowen.

Right now, New York is the only state with a law preventing specialty tiers. Ma plans to announce the specifics of her legislation on Thursday. However, state legislation does not impact self-funded health plans which cover about half of all employees with health insurance. Federal legislation is needed to change that.

(Copyright ©2011 KGO-TV/DT. All Rights Reserved.)

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