|
|
| HUMAN GENOME SCIENCES DESCRIBES ACTIVITY OF ABTHRAX AT 43RD ANNUAL INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | |
|
- Single dose of new drug protects animals from lethal effects of anthrax spores -
- In vitro and in vivo data support clinical development - - Phase 1 human safety trial progressing - ROCKVILLE, Maryland – September 15, 2003 – Human Genome Sciences, Inc. (Nasdaq: HGSI) described today results of preclinical studies presented at the 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago, Illinois, that support the clinical development of ABthrax™, a novel human monoclonal antibody drug for the prevention and treatment of anthrax infections.1 Company scientists presented two posters on September 14 that described the results of in vitro and in vivo preclinical studies of ABthrax (human monoclonal antibody to Bacillus anthracis protective antigen). The results of these preclinical studies showed that a single dose of ABthrax increases survival significantly in both rabbit and nonhuman primate models of inhalational anthrax, and provide the scientific basis for initiating clinical development of ABthrax. As previously announced, Human Genome Sciences has initiated a Phase 1 placebo-controlled, dose-escalation clinical trial to evaluate the safety, tolerability and pharmacokinetics of ABthrax in healthy adult volunteers.2 On August 19, 2003, Human Genome Sciences announced that ABthrax has received a Fast Track Product designation from the U.S. Food and Drug Administration (FDA).3 A poster entitled Selection of Potent Neutralizing Human Monoclonal Antibodies to Protective Antigen of Bacillus anthracis (Abstract # 3976) described the results of studies designed to generate and characterize human monoclonal antibodies to protective antigen that might be useful in the prevention and treatment of anthrax infection.4 Such monoclonal antibodies were developed and analyzed for their in vitro ability to bind protective antigen and inhibit protective antigen binding to its receptor. Results of these experiments demonstrate that ABthrax binds specifically and with high affinity to protective antigen and inhibits the binding of protective antigen to its receptor. In addition, selected monoclonal antibodies were evaluated in an experimental animal model for their ability to protect animals from anthrax toxin lethality. Results show that a single administration of ABthrax administered subcutaneously, intramuscularly, or intravenously provides complete protection against anthrax toxin lethality for up to three weeks. A poster entitled Protection against Inhalation Anthrax-induced Lethality by a Human Monoclonal Antibody to Protective Antigen in Rabbits and Cynomolgus Monkeys (Abstract # 3836) described results of experiments designed to evaluate the effectiveness of ABthrax in protecting against inhalation anthrax-induced lethality.5 In an experimental model of inhalation anthrax in New Zealand white rabbits, a single injection of ABthrax was administered at five different dose levels 48 hours prior to spore challenge or within one hour after spore challenge. The primary objectives of the study were survival at study day 14 and time to death. ABthrax levels and bacteremia (the amount of anthrax bacteria in the bloodstream) were evaluated at multiple time points. Results show that ABthrax significantly improved survival in rabbits compared to the control group (p< 0.0001). In addition, ABthrax significantly prolonged time to death compared to the control group (p £ 0.0002). A single injection of ABthrax administered at the highest dose within one hour after spore challenge provided 100% protection against lethality. The improvement in survival afforded by ABthrax was highly dose-dependent (p< 0.0001). Bacteremia was measured at Days 2, 7 and 14. At Day 14, all ABthrax-treated animals that survived, including two animals that were bacteremic at Days 2 and 7, respectively, were negative for anthrax bacteria in the blood. The same poster also described results of an experimental model of inhalation anthrax in cynomolgus monkeys, in which a single injection of ABthrax was administered at three different dose levels 48 hours prior to spore challenge. The primary objectives of this study were survival at study day 28 and time to death. ABthrax levels and bacteremia were evaluated at multiple time points. Results show that ABthrax significantly improved survival in monkeys compared to the control group (p < 0.011). At all evaluated dose levels, ABthrax also significantly prolonged time to death compared to the control group (p £ 0.0005). Again, the improvement in survival afforded by ABthrax was highly dose-dependent (p< 0.0002). Bacteremia was measured at Days 7, 14, 21, and 28. All ABthrax-treated animals that survived were negative for anthrax bacteria in the blood at all time points. Under the Bioterrorism Act of 2002, the FDA specified the evidence required to demonstrate the efficacy of new drug and biological products used to counter biological agents, when traditional efficacy studies in humans are not feasible.6 According to the guidelines set forth in the Bioterrorism Act, successful studies in relevant animal models will be considered sufficient to establish efficacy for licensure and marketing approval. ABthrax has been demonstrated to be effective in preventing the lethal effects of anthrax infection in two relevant models, rabbits and nonhuman primates. According to the guidelines, clinical trials will be required to establish safety, tolerability, and pharmacology, but not efficacy. Such a clinical trial of ABthrax is underway in healthy adults. Craig A. Rosen, Ph.D., President, Research and Development, said, “Results from the preclinical studies presented at the meeting demonstrate that a single dose of ABthrax administered prophylactically increases survival significantly in both rabbits and monkeys exposed by inhaling lethal doses of anthrax spores. These data provide the scientific support for the advancement of ABthrax into human safety trials. We believe ABthrax has the potential to provide significant protection against anthrax infections when given prophylactically, and may lessen the natural progression of anthrax infection and increase survival if given as a post-exposure treatment. ABthrax also may prevent and treat infections by antibiotic-resistant strains of anthrax.” William A. Haseltine, Ph.D., Chairman and Chief Executive Officer, said, “We have shown, in multiple animal models, that ABthrax is effective against high doses of inhaled anthrax spores. We are manufacturing this drug ourselves and have initiated a human safety trial. We also recently received FDA Fast Track Product designation for ABthrax, which affords us the opportunity for close cooperation with the FDA as we continue the development of this novel antibody drug. We believe that ABthrax has the potential to play an important role in the prevention and treatment of anthrax infections.” Anthrax infection is caused by a spore-forming bacterium, Bacillus anthracis, which multiplies in the body and produces lethal toxins. Most anthrax fatalities are caused by the irreversible effects of the anthrax toxins. Research has shown that protective antigen is the key facilitator of the progression of anthrax infection at the cellular level.7 After protective antigen and the anthrax toxins are produced by the bacteria, protective antigen binds to the anthrax toxin receptor on cell surfaces and forms a protein-receptor complex that makes it possible for the anthrax toxins to enter the cells. ABthrax blocks the binding of protective antigen to cell surfaces and prevents the anthrax toxins from entering and killing the cells. ABthrax is a human monoclonal antibody to Bacillus anthracis protective antigen that was discovered and developed by Human Genome Sciences. Human Genome Sciences plans to develop ABthrax for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. ABthrax has been shown to be effective in protecting against anthrax in multiple experimental models in animals. A single dose of ABthrax increases survival significantly in both rabbit and nonhuman primate models of inhalational anthrax.5 The Company is conducting a Phase 1 placebo-controlled, dose-escalation clinical trial to evaluate the safety, tolerability and pharmacokinetics of ABthrax in healthy adult volunteers. ABthrax has received a Fast Track Product designation from the U.S. Food and Drug Administration (FDA).3 The ABthrax used for preclinical and clinical studies is produced in the Company’s manufacturing facilities in Rockville, Maryland. Large-scale development and manufacture of ABthrax is dependent on government funding either under existing authority or under proposed Project Bioshield legislation. For more information about ABthrax, see www.hgsi.com/products/ABthrax.html. For more information about anthrax, please visit the Centers for Disease Control and Prevention (CDC) web site on bioterrorism and anthrax at http://www.bt.cdc.gov/agent/anthrax/index.asp. For more information about the FDA’s Fast Track Drug Development Programs, see www.fda.gov. Health professionals interested in more information about trials involving HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, www.hgsi.com/products/request.html, or by calling us at (301) 610-5790, extension 3550. Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based drugs to patients. HGS, Human Genome Sciences, and ABthrax are trademarks of Human Genome Sciences, Inc. This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences’ current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company’s unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company’s ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company’s dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company’s filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today’s date. The Company can provide no assurance that ABthrax will be effective in humans, or that any approved drug will result or be commercialized successfully. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise. # # #
Footnotes:
CONTACTS: |