Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that the results of a Phase 1 clinical trial of HGS004 (CCR5 mAb) demonstrate that it was well tolerated and exhibited antiviral activity in patients who are infected with HIV-1, the retrovirus that causes acquired immunodeficiency syndrome (AIDS). The results were reported in San Francisco in an oral presentation at the American Society for Microbiology’s 46th Annual Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
“The availability of the newer classes of antiretroviral agents has produced considerably improved outcomes in the treatment of AIDS and HIV-1 infection, but there is a significant need for novel classes of safe and effective agents that have additive or synergistic activity and a low risk of cross-resistance,” said Jacob P. Lalezari, M.D., Director, Quest Clinical Research, Assistant Clinical Professor of Medicine, UCSF/Mount Zion Hospital, San Francisco, and lead investigator for the Phase 1 trial of HGS004. “The results of the Phase 1 study of HGS004, along with preclinical data, warrant additional study of HGS004 and other therapeutic candidates in the HGS CCR5 antibody program.”
“The Phase 1 results presented at ICAAC demonstrate proof of concept for the HGS CCR5 antibody program,” said William W. Freimuth, M.D., Ph.D., Vice President, Clinical Research, Immunology, Rheumatology and Infectious Disease, HGS. “The study demonstrates that HGS004 was well tolerated and exhibited significant dose-related antiviral activity that correlates well with pharmacokinetic data and with the sensitivity of specific HIV-1 viral strains. We note that data from in vitro studies suggest that HGS101, an alternate CCR5 mAb candidate, is likely to have approximately 5.5-fold greater potency and a broader range of activity against HIV-1 viral strains than HGS004. The other attributes of HGS101 are similar to those of HGS004, including favorable pharmacokinetics, strong in vitro evidence of anti-viral activity that is additive or synergistic in combination with other therapeutic agents, and a low likelihood of the development of resistance. In the coming months, we will determine the best path forward for the HGS CCR5 mAb program.”
The Phase 1 trial of HGS004 (CCR5 mAb) was a randomized, placebo- controlled, dose-escalation, multi-center study in patients who were infected with HIV-1 and not receiving concurrent antiretroviral therapy. The primary objective was to evaluate the safety and tolerability of escalating doses of a single intravenous (IV) infusion of HGS004. The secondary objectives were to determine the pharmacokinetics of HGS004, and to assess its effect on plasma HIV-1 viral load and on CD4+ and CD8+ T-cell counts over time. Patients were followed for 56 days after study agent administration.
The results of the Phase 1 trial were reported today at ICAAC in an oral presentation entitled “A Phase 1, Randomized, Dose-Escalation, Placebo- Controlled Study of a Fully Human Monoclonal Antibody Against CCR5 (HGS004) in Patients with CCR5 Tropic HIV-1 Infection.” A total of 54 patients were randomized and enrolled into 6 dose cohorts at a ratio of 4:1 (active: placebo). In each cohort, patients received a single IV infusion of HGS004 or matching placebo (0.4 mg/kg, 2 mg/kg, 8 mg/kg, 20 mg/kg, and 40 mg/kg). The results demonstrate that HGS004 was well tolerated following administration of a single IV dose up to 40 mg/kg. A significantly higher antiviral response was observed in patients receiving HGS004 at doses of 8 mg/kg or greater. At these doses, a dose response was observed in viral load reduction at Day 14, vs. placebo or the lower-dose cohorts (p<0.0001). A viral load reduction of > or = 1.0 log was observed at Day 14 in 57.9% (11/19) of the patients receiving HGS004 at doses of 8-20 mcg, and 50% (5/10) of the patients receiving HGS004 at a dose of 40 mg/kg. At Day 28, a trend to dose response was observed for doses > or = 8mg/g, vs. placebo or the 0.4 and 2 mg/kg cohorts (p=0.0007). Increases in CD4+ and CD8+ T-cell counts from baseline were observed in the majority of subjects receiving HGS004. The pharmacokinetics of HGS004 were non-linear across the range of doses studied, with a dose-proportional C-max increase and a greater than dose-proportional AUC increase. HGS004 exhibited an elimination half life of 5-8 days. At doses of 8 mg/kg or greater, CCR5 receptor occupancy (RO) of greater than 80% was observed from Day 14 through Day 28. Significant RO was maintained through Day 56 in the three higher dose cohorts. HGS004 was well tolerated even at the highest dose of 40 mg/kg. Two treatment-related moderately severe adverse events of transient infusion- related urticarial rash were observed in the 2 mg/kg treatment cohort. Subsequent patients were pretreated with Benadryl, and no additional instances of urticarial rash were reported. There were no clinically significant laboratory abnormalities.
HGS004 is a fully human monoclonal antibody that specifically recognizes and binds the chemokine receptor CCR5, which is known to be a key facilitator of infection with human immunodeficiency virus (HIV-1). HGS004 was generated by HGS using the Abgenix XenoMouse(R) technology. The HGS CCR5 mAb program also includes HGS101, a fully human antibody which in vitro data suggest is likely to be approximately 5.5 times more potent than HGS004, with activity against a broader range of HIV-1 viral strains.
The mission of Human Genome Sciences is to discover, develop, manufacture and market innovative drugs that serve patients with unmet medical needs, with a primary focus on protein and antibody drugs.
The HGS clinical development pipeline includes drugs to treat hepatitis C, lupus, anthrax disease, cancer, rheumatoid arthritis and HIV/AIDS. The Company’s primary focus is rapid progress toward the commercialization of its two lead compounds, Albuferon(TM) for hepatitis C, and LymphoStat-B(TM) for lupus. Both compounds are expected to advance to Phase 3 clinical trials in 2006.
In June 2006, HGS announced that the U.S. Government exercised its option under an existing contract to purchase 20,000 doses of ABthrax(TM) for the treatment of anthrax disease. Other HGS compounds in clinical development include three TRAIL receptor antibodies for the treatment of hematopoietic and solid malignancies, in addition to an antibody to the CCR5 receptor for the treatment of HIV/AIDS.
For more information about HGS, please visit the Company’s web site at http://www.hgsi.com. For more information on CCR5 mAb, visit http://www.hgsi.com/products/CCR5.html. Health professionals or patients interested in inquiring about clinical trials involving HGS products in development are encouraged to inquire via the Contact Us section of the company’s web site, http://www.hgsi.com/products/request.html, or by calling us at (301) 610-5790, extension 3550.
HGS, Human Genome Sciences, ABthrax, Albuferon and LymphoStat-B 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. In addition, the Company will continue to face risks related to animal and human testing, to the manufacture of ABthrax and to FDA concurrence that ABthrax meets the requirements of the ABthrax contract. If the Company is unable to meet the product requirements associated with the ABthrax contract, the U.S. Government will not be required to reimburse the Company for the costs incurred or to purchase any ABthrax doses. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today’s date. 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.
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