ROCKVILLE, Md., Dec. 20 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that it has initiated dosing of patients in a Phase 2 clinical trial of HGS-ETR1 (mapatumumab) in combination with the chemotherapy agents paclitaxel and carboplatin as first-line therapy in patients with advanced non-small cell lung cancer.
"The majority of patients who are newly diagnosed with non-small cell lung cancer have locally advanced or metastatic disease that is currently incurable," said Philip D. Bonomi, M.D., a principal investigator in the study, and Section Director, Medical Oncology, Rush University Medical Center, Chicago. "Fewer than half of these patients are candidates for surgery. There is an urgent medical need for effective treatment options for non-small cell lung cancer because current treatment strategies have only a minimal impact on survival. We look forward to evaluating the potential of HGS-ETR1 plus chemotherapy to offer a new approach to the first-line treatment of this deadly disease."
HGS-ETR1 is a human monoclonal antibody to TRAIL receptor 1, a protein involved in programmed cell death (apoptosis). The first randomized Phase 2 trial of HGS-ETR1 is currently underway in combination with bortezomib (Velcade) in patients with advanced multiple myeloma. HGS expects to have data available from the multiple myeloma study by mid-2008. In a separate press release issued earlier today, HGS and Aegera Therapeutics Inc. announced that HGS has acquired exclusive worldwide rights (excluding Japan) to develop and commercialize AEG40826, a potent small-molecule inhibitor of multiple proteins in the IAP (inhibitor of apoptosis) family that is expected to enter Phase 1 clinical trials for the treatment of cancer in early 2008. Preclinical studies have demonstrated that AEG40826 and the HGS TRAIL receptor antibodies exhibit dramatic synergistic activity in a broad range of cancers. HGS plans to develop the TRAIL receptor antibodies and IAP inhibitors in combination with one another and in combination with other therapies.
"The TRAIL-mediated apoptosis pathway is an exciting area of cancer research, and agonistic antibodies to this target offer great promise to patients with a wide variety of cancers. HGS-ETR1 is the most advanced of these antibodies, now with two randomized Phase 2 chemotherapy combination trials ongoing," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. "In addition, with the licensing and collaboration agreement we announced today, we have strengthened our oncology franchise by adding small-molecule drugs known as IAP inhibitors, which also enhance apoptosis in cancer cells. We look forward to developing our TRAIL receptor antibodies and IAP inhibitors in combination with one another and in combination with other therapeutic agents."
About the Phase 2 Trial Design
This randomized, multi-center, open-label Phase 2 study is designed to evaluate the efficacy and safety of HGS-ETR1 in combination with carboplatin and paclitaxel as first-line therapy in the treatment of advanced non-small cell lung cancer (Stage IIIB or IV). Approximately 105 patients will be randomly assigned among three treatment groups and treated with either the two-agent combination of carboplatin and paclitaxel or the three-agent combination of carboplatin, paclitaxel and HGS-ETR1 at either 10 mg/kg or 30 mg/kg.
About Previous Results in Non-Small Cell Lung Cancer
The results of in vitro and in vivo preclinical studies demonstrate that: (1) TRAIL receptor 1 is differentially expressed on non-small cell lung cancer (NSCLC) cells compared with normal cells; (2) HGS-ETR1 specifically binds TRAIL receptor 1 and triggers NSCLC cell death through apoptosis; and (3) HGS- ETR1 inhibits NSCLC tumor growth in xenograft models of NSCLC, and can induce significant tumor regression in certain xenograft models of the disease. HGS preclinical studies also show that the activity of HGS-ETR1 in NSCLC models may be increased by co-treatment with chemotherapeutic agents including carboplatin and taxanes such as paclitaxel. The results of preclinical studies in a number of NSCLC cell lines showed that combining HGS-ETR1 with these chemotherapeutic agents resulted in increased cancer cell-killing ability despite resistance to mapatumumab alone, indicating a synergistic interaction. The combination of carboplatin, a taxane and HGS-ETR1 resulted in tumor regression and sustained reduction in tumor growth in a xenograft model of NSCLC that was significantly greater than any of the agents alone or the combination of carboplatin and a taxane.
The results of an earlier Phase 2 clinical trial of HGS-ETR1 to evaluate its safety as a single agent in patients with advanced non-small cell lung cancer showed that the drug was generally well tolerated and could be administered safely and repetitively, with no patients discontinuing therapy due to drug-related toxicity. Patients participating in the earlier study previously had received up to seven different cancer treatment regimens (median of three). Stable disease was observed in 29 percent (nine out of 32) of the patients treated, with eight patients receiving at least four cycles of therapy. The results, along with the results of other clinical and preclinical studies, support further evaluation of HGS-ETR1 in combination with chemotherapy agents.
About Non-Small Cell Lung Cancer
Non-small cell lung cancer accounts for approximately 75-80% of all lung cancers. It is estimated that more than 170,000 new cases and more than 160,000 deaths occur annually in the United States alone. It is currently the leading cause of cancer death in the U.S. in both men and women.
HGS-ETR1 (mapatumumab) is an agonistic human monoclonal antibody that directly induces cancer-cell death by specifically binding to and activating the protein known as TRAIL receptor 1. Using genomic techniques, HGS originally identified the TRAIL receptor-1 protein. The HGS-ETR1 antibody was generated by HGS through collaboration with Cambridge Antibody Technology. HGS is developing HGS-ETR1 as a potential treatment 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.
HGS management will hold a conference call today to discuss this announcement, as well as a separate announcement that HGS has acquired from Aegera Therapeutics the exclusive worldwide rights (excluding Japan) to develop and commercialize AEG40826, a potent small-molecule IAP inhibitor that is expected to enter Phase 1 clinical trials for the treatment of cancer in early 2008. The conference call will be held at 11 AM Eastern time. Participants may listen to the call by dialing 888-233-8128 or 913-312-0734, passcode 2718784, five to 10 minutes before the start of the call. A replay of the conference call will be available for several days by dialing 888-203- 1112 or 719-457-0820, passcode 2718784. This conference call also will be webcast. Interested parties who wish to listen to the webcast should visit the HGS website at www.hgsi.com. The archive of the conference call will be made available within a few hours after the call and will remain available for several days.
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. The IAP inhibitor AEG40826 is expected to enter Phase 1 clinical trials for the treatment of cancer in early 2008.
For more information about Human Genome Sciences, please visit the Company's web site at www.hgsi.com. For more information about HGS-ETR1, see www.hgsi.com/products/ETR1.html. Health professionals interested in more information about trials involving HGS products are encouraged to inquire via the Contact Us section of the HGS website, www.hgsi.com/products/request.html, or by calling (301) 610-5790, extension 3550.
ABthrax, Albuferon, LymphoStat-B, HGS and Human Genome Sciences are trademarks of Human Genome Sciences, Inc.
HGS 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.
SOURCE Human Genome Sciences, Inc.