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FDA Approves Baxter's HYQVIA for Treatment of Adults with Primary Immunodeficiency

BAX, HALO, BIOGY

Baxter International Inc. (NYSE:BAX) and Halozyme Therapeutics, Inc., (NASDAQ:HALO) today announced that the United States Food and Drug Administration (FDA) approved Baxter’s subcutaneous treatment for adult patients with primary immunodeficiency (PI), HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase].

HYQVIA is the first subcutaneous immune globulin (IG) treatment approved for PI patients with a dosing regimen requiring only one infusion up to once per month (every three to four weeks) and one injection site per infusion to deliver a full therapeutic dose of IG. The majority of PI patients today receive intravenous infusions in a doctor’s office or infusion center, and current subcutaneous IG treatments require weekly or bi-weekly treatment with multiple infusion sites per treatment.

''Patients with PI value treatments that offer efficacy, safety and tolerability. Since each person with PI responds differently to treatment, having options that meet these individual needs is critically important,'' commented Marcia Boyle, President and Founder of the Immune Deficiency Foundation. ''We commend Baxter for its significant commitment and investment in the development of HYQVIA.''

''The availability of HYQVIA has a significant impact on the treatment of PI, allowing for effective delivery of a full therapeutic dose of IG less frequently than other subcutaneous treatments (up to once a month), while maintaining the efficacy, safety and tolerability profile that is most important for patients,'' said Ludwig Hantson, Ph.D., President of Baxter BioScience. ''This approval highlights the support of the patient community for new treatment options.''

''Today’s FDA approval of HYQVIA is a significant milestone for Halozyme as it represents the first U.S. approved Biologics License Application which utilizes our rHuPH20 platform,'' commented Dr. Helen Torley, President and Chief Executive Officer of Halozyme. ''I would like to thank the talented teams at both Halozyme and Baxter for their dedication to bring a new treatment alternative to PI patients managing a life-long disease.''

Baxter expects to launch HYQVIA in the U.S. in the coming weeks. HYQVIA was approved in Europe in 2013 for adults (≥18 years) with primary immunodeficiency syndromes and myeloma or chronic lymphocytic leukemia (CLL) with severe secondary hypogammaglobulinemia and recurrent infections. It is currently being prescribed in several European countries, including Germany, Netherlands, Sweden, Norway, Denmark, Ireland and Italy.

About HYQVIA

HYQVIA is an immune globulin with a recombinant human hyaluronidase indicated for the treatment of Primary Immunodeficiency (PI) in adults.

HYQVIA is a product consisting of Immune Globulin Infusion 10% (Human) (IG 10%) and Recombinant Human Hyaluronidase (developed by Halozyme Therapeutics). The IG component, a 10% solution that is prepared from large pools of human plasma consisting of at least 98% IgG, contains a broad spectrum of antibodies and provides the therapeutic effect. The Recombinant Human Hyaluronidase of HYQVIA increases dispersion and absorption of the Immune Globulin Infusion 10% (Human).

Important Risk Information

Thrombosis may occur with immune globulin products, including HYQVIA. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. For patients at risk of thrombosis, administer HYQVIA at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity.

HYQVIA is contraindicated in patients who have a history of anaphylactic or severe systemic reactions to the administration of IgG; in IgA-deficient patients with antibodies to IgA and a history of hypersensitivity; and in patients with known systemic hypersensitivity to hyaluronidase or Recombinant Human Hyaluronidase of HYQVIA. Severe hypersensitivity reactions may occur, even in patients who have tolerated previous treatment with IgG. Patients with antibodies to IgA are potentially at greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Non-neutralizing antibodies to the recombinant human hyaluronidase component may develop. The potential exists for such antibodies to cross-react with endogenous PH20, which is known to be expressed in adult male testes, epididymis, and sperm. It is unknown whether these antibodies may interfere with fertilization in humans. The clinical significance of these antibodies is unknown.

Aseptic Meningitis Syndrome (AMS) has been reported to occur with IgG products, including Immune Globulin Infusion 10% (Human) administered intravenously and subcutaneously. Discontinuation of IgG treatment has resulted in remission of AMS within several days without sequelae. The syndrome usually begins within several hours to two days following intravenously administered IgG, perhaps more frequently in association with high dose (2 g/kg) intravenously administered IgG.

IgG products, including HYQVIA, contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells (RBC) with IgG. These antibodies may cause a positive direct antiglobulin reaction and hemolysis. Acute intravascular hemolysis has been reported following intravenously administered IgG, including Immune Globulin Infusion 10% (Human) administered intravenously, and delayed hemolytic anemia can develop due to enhanced RBC sequestration.

Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur upon use of IgG products administered intravenously, especially those containing sucrose. HYQVIA does not contain sucrose. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk for developing acute renal failure.

Infusion into or around an infected area can spread a localized infection. Do not infuse HYQVIA into these areas due to potential risk of spreading a localized infection. Non-cardiogenic pulmonary edema (TRALI) may occur with intravenously administered IgG and has been reported to occur with Immune Globulin Infusion 10% (Human) administered intravenously. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever.

Because the Immune Globulin Infusion 10% (Human) of HYQVIA is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant CJD (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens. No cases of viral transmission or CJD have been associated with HYQVIA.

After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield false positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Common adverse reactions observed in clinical trials in >5% of subjects were: local reactions, headache, antibody formation against recombinant human hyaluronidase (rHuPH20), fatigue, nausea, pyrexia, and vomiting.

Please see accompanying full prescribing information, including boxed warning for HYQVIA at:
http://www.baxter.com/downloads/healthcare_professionals/products/HYQVIA_PI.pdf.

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.

About Halozyme Therapeutics

Halozyme Therapeutics is a biopharmaceutical company dedicated to developing and commercializing innovative products that advance patient care. With a diversified portfolio of enzymes that target the extracellular matrix, the Company's research focuses primarily on a family of human enzymes, known as hyaluronidases, which increase the absorption and dispersion of biologics, drugs and fluids. Halozyme's pipeline addresses therapeutic areas, including oncology, diabetes, and dermatology that have significant unmet medical need. The Company markets Hylenex® recombinant (hyaluronidase human injection) and has partnerships with Roche, Pfizer, and Baxter. Halozyme is headquartered in San Diego. For more information on how we are innovating, please visit our corporate website at www.halozyme.com.

This release includes forward-looking statements concerning HYQVIA, including expectations with regard to its planned commercial launch in the US. 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: actions of regulatory bodies and other governmental authorities; satisfaction of regulatory and other requirements; changes in laws and regulations; product quality or supply or patient safety issues; and other risks identified in each of the company's most recent filings on Form 10-K and other SEC filings, all of which are available on their respective websites. Neither Baxter nor Halozyme undertakes to update its forward-looking statements.



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