Deerfield, Ill. - March 13, 2015
Baxter International Inc. (NYSE:BAX) today announced positive results from its Phase III clinical trial evaluating the safety and efficacy of BAX 817, an investigational recombinant factor VIIa (rFVIIa) treatment for people with hemophilia A or B who develop inhibitors.
The prospective, open-label, randomized, multicenter trial was designed to assess the safety and efficacy of BAX 817 in male patients ages 12 to 65 with hemophilia A or B with inhibitors over a 6-month period using on-demand therapy. The trial met its primary endpoint of successful resolution of acute bleeding episodes at 12 hours with both on-demand treatment regimens, dosing either 3x90 µg/kg or 1x270 µg/kg, with an overall success rate of 92 percent (98 percent and 85 percent in each dosing group, respectively). Further, 89 percent of patients in the trial achieved sustained bleeding control for all acute bleeding episodes 24 hours after infusion.
"The development of inhibitors remains one of the most significant challenges in treating hemophilia, as it may place patients at increased risk for life-threatening complications resulting from difficult-to-treat bleeding episodes," said John Orloff, M.D., vice president and global head of research and development at Baxter BioScience. "These positive results reflect our commitment to addressing the complex treatment of hemophilia patients with inhibitors, and reinforce our legacy of advancing hemophilia care worldwide."
No patients developed inhibitors or binding antibodies to BAX 817, and none discontinued treatment due to an adverse event (AE). One patient was hospitalized following a traumatic muscle bleed that did not respond to BAX 817. Non-serious AEs observed in the trial were generally consistent with the underlying disease or other etiology, and were all deemed to be unrelated to treatment.
Full data from the trial, including additional efficacy and safety outcomes, will be presented at a medical meeting later in 2015. The company plans to initiate regulatory submissions aligned to manufacturing expansions currently underway. Baxter remains committed to advancing our portfolio in inhibitor management. If approved, BAX 817 would broaden the existing portfolio of hemophilia and inhibitor treatments within Baxter's biopharmaceutical business, including FEIBA [Anti-Inhibitor Coagulant Complex] and the recently approved OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence] for acquired hemophilia A.
FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:
- Control and prevention of bleeding episodes
- Perioperative management
- Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation Factor VIII or coagulation Factor IX.
Detailed Important Risk Information
WARNING: THROMBOEMBOLIC EVENTS
- Thromboembolic events have been reported during post-marketing surveillance, particularly following the administration of high doses and/or in patients with thrombotic risk factors.
- Monitor patients receiving FEIBA for signs and symptoms of thromboembolic events.
The use of FEIBA is contraindicated in patients with:
- Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system
- Disseminated intravascular coagulation (DIC)
- Acute thrombosis or embolism (including myocardial infarction)
Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur with FEIBA, particularly following the administration of high doses (above 200 units per kg per day) and/or in patients with thrombotic risk factors.
Infusion of FEIBA should not exceed a dose of 100 units per kg body weight every 6 hours and daily doses of 200 units per kg body weight. Monitor patients receiving more than 100 units per kg of body weight of FEIBA for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue the infusion and initiate appropriate diagnostic and therapeutic measures.
Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur following the infusion of FEIBA. The symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. These reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of FEIBA and provide appropriate supportive care.
Because FEIBA is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting.
The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.
Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended.
OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence] is indicated for the treatment of bleeding episodes in adults with acquired hemophilia A.
Limitations of Use:
- Safety and Efficacy of OBIZUR has not been established in patients with baseline anti-porcine factor VIII inhibitor titer greater than 20 BU.
- OBIZUR is not indicated for the treatment of congenital hemophilia A or von Willebrand disease.
Detailed Important Risk Information
OBIZUR is contraindicated in patients who have had life-threatening hypersensitivity reactions to OBIZUR or its components (including traces of hamster proteins).
WARNINGS & PRECAUTIONS
Hypersensitivity reactions can occur with OBIZUR. OBIZUR contains trace amounts of hamster proteins. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest-tightness, dyspnea, hypotension, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if allergic or anaphylactic-type reactions occur.
Inhibitory antibodies to OBIZUR have occurred. Monitor patients for the development of antibodies to OBIZUR by appropriate assays. If the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled after OBIZUR administration, suspect the presence of an anti-porcine factor VIII antibody. If such inhibitory antibodies to anti-porcine factor VIII are suspected and there is a lack of clinical response, consider other therapeutic options.
Monitoring Laboratory Tests
- Perform one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained
- Monitor factor VIII activity 30 minutes and 3 hours after initial dose
- Monitor factor VIII activity 30 minutes after subsequent doses
- Monitor the development of inhibitory antibodies to OBIZUR. Perform a Nijmegen Bethesda inhibitor assay if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of OBIZUR. Use Bethesda Units (BU) to report inhibitor levels.
Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.
About Baxter in Hemophilia
Baxter has more than 60 years experience in hemophilia and has introduced a number of therapeutic firsts for hemophilia patients. Baxter has the broadest portfolio of hemophilia treatments in the industry and is able to meet individual therapy choices, providing a range of options at each treatment stage. The company's work focuses on optimizing hemophilia care and improving the lives of people worldwide living with bleeding disorders.
About Baxter BioScience
Baxter BioScience is a leading provider of therapeutic treatments that save, sustain and improve the lives of people with rare conditions, chronic diseases or limited treatment options. Supported by advanced technical and manufacturing expertise, Baxter BioScience has a broad pipeline built on a legacy of innovation in bleeding disorders and immunology and is expanding to address emerging opportunities in technology platforms such as gene therapy and biosimilars. By mid-2015, Baxter expects to establish the BioScience business as a separate, publicly traded, innovation-oriented biopharmaceutical company.
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 BAX 817, including expectations with regard to clinical data and regulatory filings, as well as plans to separate Baxter's biopharmaceutical and medical products businesses and related research and development strategies. 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; additional clinical results; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; 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.