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| HUMAN GENOME SCIENCES REPORTS RESULTS OF PHASE 1 CLINICAL TRIALS OF HGS-ETR1 (TRAIL-R1 MAB) IN PATIENTS WITH ADVANCED CANCERS | |
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- Results of ongoing Phase 1 clinical studies demonstrate safety and tolerability of HGS-ETR1 and provide preliminary evidence of biological activity - - Data presented at ASCO support further evaluation in Phase 2 clinical trials - ROCKVILLE, Maryland – June 7, 2004 – Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that the results of ongoing Phase 1 clinical trials demonstrate the safety and tolerability of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL Receptor-1) in cancer patients with advanced solid tumors or non-Hodgkin’s lymphoma, and support further evaluation of HGS-ETR1 in Phase 2 clinical trials. Safety, pharmacokinetic and biological activity data from two Phase 1 studies of HGS-ETR1 were presented today at the 40th Annual Meeting of the American Society of Clinical Oncology (ASCO) in New Orleans. A poster entitled “A Phase 1 and Pharmacokinetic Study of HGS-ETR1, A Fully Human Monoclonal Antibody to TRAIL-R1, in Patients with Advanced Solid Tumors” (Abstract #3060) presented data on thirty-seven patients treated to date in an ongoing multi-center, open-label, dose-escalation clinical trial.1 Thirty-three of the thirty-seven patients had received prior chemotherapy. The median number of treatment regimens previously experienced was two, and ranged as high as nine. The patients were enrolled into seven cohorts (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg) and received HGS-ETR1 administered intravenously every 28 days. The primary purpose of the ongoing Phase 1 trial is to determine the safety, maximum tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of HGS-ETR1 in patients with relapsed or refractory advanced tumors. Disease response also is being evaluated. Available tumor tissue samples from patients participating in the trial will be evaluated for expression of the TRAIL Receptor-1 protein using immunohistochemical (IHC) techniques. Results to date of the ongoing Phase 1 clinical trial demonstrate that HGS-ETR1 can be administered safely and repetitively to patients with advanced solid malignancies at doses up to and including 10 mg/kg intravenously every 28 days. No evidence of drug-related hematologic or hepatic toxicity has been observed at the doses administered to date. The MTD has not been reached, and accrual in the trial continues at a dose of 10 mg/kg. Dose-proportional pharmacokinetics were observed up to a dose of 1.0 mg/kg. In the four patients treated at the 3.0 mg/kg dose level, the terminal elimination half-life of HGS-ETR1 was prolonged, averaging 25 days. Plasma concentrations were observed to be in a range associated with preclinical evidence of biological activity. Durable stable disease for greater than six months was observed in one patient with metastatic sarcoma. Regression of a supraclavicular lymph node, with radiographic evidence of stable disease in the liver, was observed in one patient with hepatocellular carcinoma who continues on treatment. A poster entitled “Phase 1 Study of a Fully Human Monoclonal Antibody to the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Death Receptor 4 (TRAIL-R1) in Subjects with Advanced Solid Malignancies or Non-Hodgkin’s Lymphoma” (Abstract #2533) presented data on twenty patients treated to date in an open-label, dose-escalation clinical trial currently ongoing at two centers in Canada.2 All patients admitted to the trial have relapsed or refractory disease and had received prior anti-cancer treatments (chemotherapy, radiotherapy, or hormone therapy). The twenty patients were enrolled into four cohorts (0.01, 0.03, 0.3, or 3.0 mg/kg) and received HGS-ETR1 administered intravenously every 28 days. Patients currently are being enrolled into a cohort at 10 mg/kg. The study design calls for enrollment of an additional cohort at a dose of 20 mg/kg. Patients are treated every 28 days in the absence of disease progression or dose-limiting toxicities. The primary objective of the ongoing Phase 1 clinical trial is to evaluate the safety and tolerability of repeated doses of HGS-ETR1 administered intravenously in patients with advanced solid tumors or non-Hodgkin’s lymphoma. The secondary objectives are to evaluate the pharmacokinetics of repeated doses of HGS-ETR1 and to assess tumor response. Results to date of the ongoing clinical trial demonstrate that HGS-ETR1 is well tolerated with no clearly attributable toxicities and that the MTD has not been reached. Preliminary data indicate that the pharmacokinetics of HGS-ETR1 are linear up to 0.3 mg/kg. Stable disease has been observed in five patients. The trial continues to enroll patients. An additional poster presented at ASCO (Abstract #6595) described the results of a preclinical study of the in vitro activity of HGS-ETR1 and HGS-ETR2 (agonistic human monoclonal antibody to TRAIL Receptor-2) in five lymphoma cell lines and twenty-seven primary lymphoid malignancy samples.3 The data presented demonstrate that HGS-ETR1 and HGS-ETR2 can induce programmed cell death in a wide variety of cultured and primary tumor cells of lymphoid origin, and support the continued clinical development of both drugs in patients with lymphoid malignancies. Anthony Tolcher, M.D., Director of Clinical Research at the Institute for Drug Development of the Cancer Therapy and Research Center, and Clinical Professor, Department of Medicine/Oncology, University of Texas Health Sciences Center, San Antonio, Texas, said, “Our understanding of the biological function of the TRAIL Receptors continues to grow, as we begin to evaluate HGS-ETR1 in clinical trials. TRAIL Receptor-1 is widely expressed on human tumor cells, and appears to regulate the activation of caspases, a family of proteins that are among the major effectors of apoptosis, or programmed cell death. HGS-ETR1 binds to the TRAIL-R1 receptor and induces activation of the extrinsic pathway of apoptosis, causing cancer cells to die. The initial clinical results presented at ASCO demonstrate that HGS-ETR1 is well tolerated. We also have observed preliminary evidence of biological activity. Further evaluation of HGS-ETR1 is appropriate in Phase 2 clinical trials.” David C. Stump, M.D., said, “The initial results presented from our ongoing Phase 1 clinical trials of HGS-ETR1 are encouraging. The data show that HGS-ETR1 is well tolerated and can be safely and repetitively administered to patients with advanced solid tumors. We have observed no evidence of drug-related hematological or hepatic toxicity, and we have not yet reached the maximum tolerated dose. I am particularly encouraged that stable disease has been observed in a number of patients in the two trials. We look forward to continuing to elucidate the potential role of HGS-ETR1 as a treatment for solid tumor and other malignancies, and we plan to advance HGS-ETR1 to Phase 2 clinical trials in 2004.” For more information about HGS-ETR1, see www.hgsi.com/products/TRAIL-R1_mAb.html. 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 (240) 314-4400, extension 3550. Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based protein and antibody drugs to patients. HGS and Human Genome Sciences 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. 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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