ROCKVILLE, Md., Oct. 24 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. today announced that HGS-ETR2 (lexatumumab) was safe and well tolerated in combination with four different standard chemotherapy regimens in a Phase 1b clinical trial in patients with a wide range of cancer types. Objective responses were reported for two patients, and stable disease was observed in 22 patients. The trial was the first reported human study of an antibody to TRAIL receptor 2 in combination with chemotherapy. The results were presented today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in San Francisco.
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The company also presented preclinical data demonstrating that HGS-ETR1 (mapatumumab) and HGS-ETR2 in combination with chemotherapy synergistically enhanced anti-tumor activity in cholangiocarcinoma (cancer of the bile ducts). In a xenograft model of cholangiocarcinoma, the results demonstrated that HGS- ETR1 and either co-treatment or pre-treatment with cisplatin and gemcitabine were more effective than chemotherapy or HGS-ETR1 alone.
“The clinical and preclinical results presented today add to a growing body of data showing that our agonistic antibodies to TRAIL receptors 1 and 2 offer a targeted mechanism of cancer-cell death that can be administered safely in combination with a variety of proven chemotherapies,” said Gilles Gallant, B. Pharm., Ph.D., Vice President, Clinical Research - Oncology, HGS. “The data suggest that both pre-treatment and co-treatment with chemotherapy may be effective approaches to the use of TRAIL receptor antibodies for the treatment of cancer.”
About the Results of the Phase 1b Trial of HGS-ETR2
In the first reported clinical trial of a TRAIL receptor 2 agonist in combination with chemotherapy, 41 patients with a wide range of solid malignancies received HGS-ETR2 plus a full-dose regimen of chemotherapy (gemcitabine, pemetrexed, doxorubicin or FOLFIRI). Four to seven patients in each chemotherapy cohort received HGS-ETR2 intravenously at doses of either 5 mg/kg or 10 mg/kg.
The results showed that HGS-ETR2 in combination with full-dose chemotherapy was generally safe and well tolerated. Objective responses were reported for two patients (a colorectal cancer patient in the FOLFIRI arm, and a small-cell lung cancer patient in the doxorubicin arm). Stable disease was observed in 22 patients. Overall, the nature and severity of adverse events were consistent with the underlying disease and known safety profile of the chemotherapeutic regimens. The pharmacokinetics of HGS-ETR2 were not influenced by the chemotherapeutic agents, nor did HGS-ETR2 affect the pharmacokinetics of gemcitabine, doxorubicin or irinotecan. Further studies of HGS-ETR2 in combination with chemotherapy are warranted.
“The results of the Phase 1b study of HGS-ETR2 show that it is well tolerated and can be repetitively administered in combination with standard chemotherapy agents in patients with a variety of advanced solid malignances,” said Norma Lynn Fox, Ph.D., Senior Director, Clinical Research, HGS. “We were encouraged by the observation of objective responses in two patients and stable disease in more than 20 patients, a number of whom remained on treatment for more than five months before progression of disease.”
About the Preclinical Results in Cholangiocarcinoma
Results were also presented from preclinical studies that evaluated the ability of HGS-ETR1 and HGS-ETR2 to kill cancer cells and inhibit tumor growth as single agents and in combination with chemotherapy agents: cisplatin, gemcitabine or 5-fluorouracil. Efficacy was measured using cell toxicity assays in cholangiocarcinoma cell lines (in vitro) and in a xenograft cholangiocarcinoma tumor model (in vivo).
The in vitro study showed that HGS-ETR1 or HGS-ETR2 combined with either a pre-treatment or a co-treatment chemotherapy regimen induced additive or synergistic cytotoxicity. Co-treatment with the triplet combination of cisplatin, gemcitabine and either HGS-ETR1 or HGS-ETR2 was more effective than either single agent alone in all cell lines, with most triplet combinations inducing greater than 90 percent cell toxicity. In a xenograft model of cholangiocarcinoma, the combination of HGS-ETR1, cisplatin and gemcitabine significantly inhibited tumor growth, including tumor regression observed at a dose of 8 mg/kg of cisplatin.
About the HGS TRAIL Receptor Antibodies
HGS-ETR1 and HGS-ETR2 are agonistic human monoclonal antibodies that directly induce cancer-cell death by specifically binding to and activating the proteins known as TRAIL receptors 1 and 2, respectively. Using genomic techniques, HGS originally identified the TRAIL receptor-1 and TRAIL receptor- 2 proteins. The HGS-ETR1 and HGS-ETR2 antibodies were generated by HGS through collaboration with Cambridge Antibody Technology. HGS is developing HGS-ETR1 and HGS-ETR2 as potential treatments for a broad range of cancers.
GlaxoSmithKline (GSK) has exercised its option under a June 1996 agreement to develop and commercialize HGS-ETR1 jointly with HGS. Under the terms of the agreement, GSK and HGS will share equally in Phase 3/4 development costs, and will share equally in sales and marketing expenses and profits of any product commercialized.
About Human Genome Sciences
The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs.
The HGS clinical development pipeline includes novel drugs to treat hepatitis C, lupus, anthrax disease, cancer and other immune-mediated diseases. The Company’s primary focus is rapid progress toward the commercialization of its two key lead drugs, Albuferon(R) (albinterferon alfa- 2b) for hepatitis C and LymphoStat-B(R) (belimumab) for lupus. Phase 3 clinical trials of both drugs are ongoing.
ABthrax(TM) (raxibacumab) is in late-stage development for the treatment of anthrax disease, and the Company is on track to begin the delivery in 2008 of 20,000 doses of ABthrax to the Strategic National Stockpile under a contract entered into with the U.S. Government in June 2006. Other HGS drugs in clinical development include two TRAIL receptor antibodies for the treatment of cancers.
For more information about HGS, please visit the Company’s Web site at www.hgsi.com. To view the AACR-NCI-EORTC poster presentation reporting results of the Phase 1b clinical trial of HGS-ETR2 in combination with chemotherapy, click here. To view the poster presentation reporting results of the preclinical studies of HGS-ETR1 and HGS-ETR2 with chemotherapy in cholangiocarcinoma, click here. Health professionals or patients interested in HGS-ETR1 or HGS-ETR2 clinical trials or other studies involving HGS products may inquire via the Contact Us section of the Company’s web site, www.hgsi.com/products/request.html, or by calling us at (301) 610-5790, extension 3550.
Safe Harbor Statement
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 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.
CONTACT: Jerry Parrott, Vice President, Corporate Communications,
+1-301-315-2777, Kate de Santis, Director, Investor Relations,
+1-301-251-6003, both of Human Genome Sciences, Inc.
Web site: http://www.hgsi.com/
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