The New England Journal of Medicine Publishes Study Investigating the Safety and Efficacy of Baxter's Cell-Based Pandemic, Avian Flu Vaccine
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First scientific, peer-reviewed publication showing the candidate vaccine induced neutralizing antibodies against widely divergent H5N1 virus
DEERFIELD, Ill., June 11, 2008 - Baxter International Inc. (NYSE: BAX) announced publication in the June 12, 2008 issue of The New England Journal of Medicine (NEJM) of data demonstrating Baxter's candidate avian influenza (H5N1) vaccine, CELVAPAN, met Phase I/II trial endpoints for safety and immunogenicity (generating a functional immune response). This is the first peer-reviewed publication of study results for CELVAPAN, the first cell culture-derived avian influenza vaccine to undergo clinical evaluation. The primary authors of the manuscript are Hartmut J. Ehrlich, MD, vice president of global research and development for Baxter's BioScience business, and Noel Barrett, vice president of Baxter's vaccines research.
"Cell culture technology could represent the future of influenza vaccine production," said John Oxford, professor of Virology, The Queen Mary School of Medicine, London, United Kingdom. "Baxter has demonstrated the ability to rapidly make large quantities of the vaccine that may protect people against divergent H5N1 viruses."
Based on manufacturing processes, Vero cell technology may offer several advantages versus conventional egg-based vaccine technology. Baxter's Vero cell manufacturing process is more rapid due to its ability to use a "native" virus that does not need to be modified to allow growth in chicken eggs, therefore accelerating vaccine production.
"CELVAPAN combines innovative science and breakthrough production technology with the aim of protecting people against an H5N1 pandemic flu infection," said Hartmut J. Ehrlich, MD. "This is an immunogenic vaccine without the need for an adjuvant to boost the immune response."
About CELVAPAN
CELVAPAN is manufactured in a cell culture-based system in Bohumil, Czech Republic, at one of the largest cell culture vaccine production facilities in the world. Vero cell technology uses a well-established cell line originally derived from African green monkey kidneys in 1962. A continuous cell line has been derived from these cells so that an unlimited supply of cells is available without the requirement of generating additional cells from animals.
Baxter's candidate avian flu vaccine is derived from the H5N1 strain A/Vietnam/1203/2004. Its antigen composition and structure are identical to the actual virus circulating in nature without the need to enhance an immune response by including adjuvants, additives that may cause side effects. In this Phase I/II study, CELVAPAN induced an immune response that is similar to the body's defense against a natural virus infection. Earlier this year CELVAPAN was accepted for licensure review by the Committee for Medicinal Products for Human Use within the European Medicines Agency, making it the first cell culture-based pandemic influenza vaccine to be reviewed by the regulatory authority. The U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is also conducting a trial with Baxter's CELVAPAN in the United States.
Phase I/II Clinical Trial Results
The randomized Phase I/II study enrolled 284 subjects in Austria and Singapore (ages 18-45) and met its immunogenicity and safety endpoints. The study mainly investigated the ability of the vaccine to induce substantial levels of cross-immunity against divergent H5N1 strains.
The trial tested four different antigen concentrations ranging from 3.75µg to 30µg; 7.5µg and 15µg formulations were studied with and without adjuvant (additive). Statistically, the non-adjuvanted formulations induced the highest rates of subjects with a titer (antibody concentration in the blood) more than 1:20 after the first (40.5 percent and 39.5 percent for 7.5 µg and 15 µg) and second (76.2 percent and 70.7 percent for 7.5 µg and 15 µg) vaccinations, demonstrating this vaccine generates a robust immune response.
Regarding seroconversion (development of antibodies) or the percent of subjects demonstrating a more than four-fold increase in titer after immunization, the highest responses were again seen with the 7.5 μg and 15 μg non-adjuvanted formulations, with 69.0 percent and 68.3 percent seroconversion respectively.
High levels of cross-reactivity were demonstrated against the A/Hong Kong strain with the 7.5 µg and 15 µg non-adjuvanted formulations (76.2 percent and 78.0 percent, respectively, with neutralizing titer more than 1:20). The responses against the clade 2 strain were somewhat lower (45.2 percent and 36.6 percent with NT titers greater than or equal to 1:20 for the 7.5 µg and 15 µg non-adjuvanted formulations, respectively). This demonstrates the ability of the vaccine to induce cross-reactive immune responses against divergent H5N1 strains.
The most common side effects were injection site reactions, headaches and fatigue, and the most common local reaction was pain at the injection site.
Baxter's Pre-Pandemic Planning Efforts
Baxter works closely with governments worldwide on pandemic preparation. The company has delivered several million doses of CELVAPAN to various governments around the world. In 2006, Baxter entered into a pandemic preparedness contract with the Austrian Ministry of Health to supply 16 million doses of pandemic influenza vaccine in the event a pandemic is declared. The company also delivered a stockpile of two million doses of CELVAPAN to the U.K. Department of Health as part of an agreement announced in February 2006. To improve access to treatment in developing countries, Baxter also supports the World Health Organization's pandemic planning programs through participation in a planned international stockpile program.
Baxter is also working with the NIAID in partnership with Fisher BioServices Inc., and with the U.S. Department of Health and Human Services in partnership with DVC LLC, a Computer Science Corporation Company, to further develop Vero cell culture-based candidate pandemic and seasonal influenza vaccines. Baxter is working with the U.S. Department of Health and Human Services, in partnership with DynPort Vaccine Company LLC, a Computer Science Corporation Company, on a seasonal Phase III clinical trial that is currently underway in the United States and also plans to initiate a pandemic Phase I trial later this year in the United States with an H5N1 Indonesia strain vaccine. Baxter is also working with the NIAID in partnership with Fisher BioServices Inc. on a pandemic Phase I trial in the United States using the H5N1 Vietnam strain.
About Pandemic Flu
A pandemic is a global disease outbreak of a virus for which there is little or no immunity in the human population, causing serious illness and spreading easily person-to-person worldwide. Most cases of avian flu infection in humans have resulted from direct or close contact with infected poultry (e.g., domesticated chicken, ducks, and turkeys) or surfaces possibly contaminated from feces of infected birds. Avian influenza infection follows an unusually aggressive clinical course, with rapid deterioration and high fatality. Primary viral pneumonia and multi-organ failure have been common among people who have become ill with avian influenza.
About Baxter
Baxter International Inc., through its subsidiaries, assists healthcare professionals and their patients with treatment of complex medical conditions, including hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other indications. The company applies its expertise in medical devices, pharmaceuticals and biotechnology to make a meaningful difference in patients' lives.
This release includes forward-looking statements concerning the company's vaccine products, including with respect to clinical trials, licensures, and the advantages of the vaccine products. 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 for timely commencement of additional clinical trials; additional clinical results demonstrating the safety and efficacy of the products; market acceptance of vaccines developed with Vero cell technology relative to egg-based or other alternatives; continued public commitment to addressing avian flu and other pandemic threats including additional experience producing such vaccines at a large scale; and other risks identified in the company's most recent filing on Form 10-Q and other SEC filings, all of which are available on the company's web site. The company does not undertake to update its forward-looking statements.