Human Genome Sciences, Inc. Reports Results Of Phase 2 Clinical Trial Of HGS-ETR1 In Patients With Advanced Colorectal Cancer

ROCKVILLE, Md., Nov. 1 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. announced today that the results of a Phase 2 clinical trial demonstrate that HGS-ETR1 (mapatumumab) is well tolerated and can be administered safely in patients with advanced colorectal cancer.

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The results were presented in Paris today at ECCO 13, the European Cancer Conference, in a poster entitled "Results of a Phase 2 Trial of HGS-ETR1 (Agonistic Human Monoclonal Antibody to TRAIL Receptor 1) in Subjects with Relapsed or Refractory Colorectal Cancer (CRC)."(1) The Phase 2 trial, which was conducted in Germany, was an open-label study to evaluate the efficacy, safety and tolerability of HGS-ETR1 as monotherapy in patients with relapsed or refractory colorectal cancer.(2-3) Data were presented on 38 patients with relapsed or refractory Stage IIIB, IV or recurrent colorectal cancer. Patients enrolled in the trial received up to six cycles of treatment in the absence of disease progression. HGS-ETR1 was administered as an intravenous infusion at 20 mg/kg at 14-day intervals in cycles 1 and 2, and at 10 mg/kg at 14-day intervals in cycles 3-6. The primary objective of the study was to evaluate tumor response after every third treatment (approximately every 6 weeks). Safety and tolerability were assessed as secondary endpoints. Several additional indicators of disease activity also were evaluated, including time to response, duration of response, and progression-free survival. Plasma concentrations of HGS-ETR1 were determined for use in a population pharmacokinetic analysis.

Patients participating in the study had received up to 6 previous cancer treatment regimens (median of 3). The data presented demonstrated that HGS- ETR1 was well tolerated and can be administered safely to relapsed or refractory CRC patients. One patient discontinued therapy due to an adverse event in which the possible contribution of HGS-ETR1 could not be ruled out completely. Stable disease was observed in 31.6% (12/38) of the patients treated, with a median duration of 2.6 months. Plasma concentrations in the CRC study population were within the range expected, based on Phase 1 and Phase 2 results to date.(4-19)

Professor Dr. Siegfried Seeber, principal investigator and Director, University Clinic for Internal Medicine (Tumor Research), West German Tumor Center, University of Essen, Germany, said, "Fewer than ten percent of the patients who develop metastatic colorectal cancer survive for five years.(20- 23) The prognosis for these patients continues to be poor, although it has been demonstrated that patients with advanced colorectal cancer are able to benefit clinically from combinations of chemotherapeutic agents and, more recently, monoclonal antibodies.(24-38) The medical need for effective new therapeutic agents continues to be significant. The results of the Phase 2 study of HGS-ETR1 in these heavily pretreated patients with relapsed or refractory colorectal cancer, together with preclinical observations, support the continued evaluation of HGS-ETR1 in combination with chemotherapy for the treatment of colorectal cancer."

David C. Stump, M.D., Executive Vice President, Drug Development, said, "The Phase 2 data presented at ECCO demonstrated that HGS-ETR1 can be safely and repetitively administered to patients with advanced colorectal cancer. The patients enrolled in this study had received multiple anti-cancer treatment regimens before entering the trial of HGS-ETR1. We note that stable disease was observed in a number of these very ill patients, with a median duration of 2.6 months. The results warrant further evaluation of HGS-ETR1 in combination with chemotherapy to determine its appropriate role in the treatment of colorectal cancer. In August 2005, we reported the results of a Phase 2 study of HGS-ETR1 in patients with non-small cell lung cancer. In June 2005, we reported the interim results of a Phase 2 study of this drug in patients with advanced non-Hodgkin's lymphoma, and we anticipate presentation of the full data in non-Hodgkin's lymphoma at the Annual Meeting of the American Society of Hematology in December. Based on the preclinical and clinical results to date, we look forward to continuing the development of HGS-ETR1 in combination with chemotherapy in a broadening program of clinical study."

GlaxoSmithKline has exercised its option under a June 1996 agreement to develop and commercialize HGS-ETR1 jointly with Human Genome Sciences. Under the terms of the agreement, GSK and Human Genome Sciences will share equally in Phase 3/4 development costs, and will share equally in sales and marketing expenses and profits of any product that is commercialized under the agreement, under a co-development and co-promotion agreement, the remaining terms of which are being negotiated by the parties.(39)

Human Genome Sciences, using genomic techniques, originally identified the TRAIL receptor-1 protein as a member of the tumor necrosis factor receptor super-family. The company's own studies, as well as those conducted by others, show that TRAIL receptor 1 plays a key role in triggering apoptosis, or programmed cell death, in human tumors. Human Genome Sciences took the approach of developing human monoclonal antibodies that would bind to the receptor and stimulate TRAIL receptor-1 protein to trigger apoptosis in cancer cells, in much the same way that the native TRAIL ligand (tumor necrosis factor-related apoptosis-inducing ligand) does, but with the advantage of a longer serum half-life and an exclusive specificity for TRAIL receptor 1. Human Genome Sciences' own clinical and preclinical studies, along with published results in the scientific literature, demonstrate that agonistic antibodies to the death domain-containing TRAIL receptors have significant potential to provide novel therapeutic options to patients with a variety of cancer types.(4-19), (40-54)

The TRAIL receptor-1 agonistic human monoclonal antibody, HGS-ETR1, was generated through a collaboration between Human Genome Sciences and Cambridge Antibody Technology.(55) The drug is produced in the Human Genome Sciences clinical manufacturing facilities located in Rockville, Maryland. Human Genome Sciences holds the commercial rights to the drug.

Colorectal cancer is the second-leading cause of cancer-related deaths in Western Europe and the United States (after lung cancer). The overall five- year survival of patients with colorectal cancer is approximately fifty percent. Fewer than ten percent of the patients who develop metastatic colorectal cancer survive for five years.

Human Genome Sciences is a company with the mission to discover, develop, manufacture and market innovative drugs that serve patients with unmet medical needs, with a primary focus on protein and antibody drugs.

For more information about HGS-ETR1, see http://www.hgsi.com/products/ETR1.html. Health professionals interested in more information about trials involving Human Genome Sciences products 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 (301) 610-5790, extension 3550.

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.

Footnotes: 1. Kanzler S, Trarbach T, Heinemann V, Kohne CH, Seeber S, et al. Results of a Phase 2 trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL receptor 1) in subjects with relapsed or refractory colorectal cancer (CRC). ECCO 13 - the European Cancer Conference, 2005: Abstract #630. 2. (HGSI Press Release) Human Genome Sciences Completes Patient Enrollment in a Phase 2 Clinical Trial of HGS-ETR1 for the Treatment of Colorectal Cancer. February 23, 2005. 3. (HGSI Press Release) Human Genome Sciences Initiates a Phase 2 Clinical Trial of HGS-ETR1 in Patients with Colorectal Cancer. October 13, 2004. 4. Bonomi P, Greco FA, et al. Results of a Phase 2 trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL receptor 1) in subjects with relapsed/recurrent non-small cell lung cancer. 11th World Conference on Lung Cancer. July 4, 2005. Abstract #1851. 5. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 2 Clinical Trial of HGS-ETR1 in Patients with Non-Small Cell Lung Cancer. July 5, 2005. 6. Younes A, et al. Activity of selective agonistic monoclonal antibodies to TRAIL death receptors R1 and R2 in primary and cultured tumor cells of lymphoid origin. 9th International Conference on Malignant Lymphoma, 2005. Oral presentation. 7. (HGSI Press Release) Human Genome Sciences Reports Interim Results of Phase 2 Clinical Trial of HGS-ETR1 in Patients with Advanced Non- Hodgkin's Lymphoma. June 13, 2005. 8. Pacey S, et al. Phase 1 and pharmacokinetic study of HGS-ETR2, a human monoclonal antibody to TRAIL-R2, in patients with advanced solid malignancies. 2005 Annual Meeting of the American Society of Clinical Oncology (ASCO), Orlando, Florida. Abstract #3055. 9. Hotte SJ, et al. HGS-ETR1, a Fully Human Monoclonal Antibody to the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 1 (TRAIL-R1) in Patients with Advanced Solid Cancer: Results of a Phase 1 Trial. 2005 Annual Meeting of the American Society of Clinical Oncology (ASCO), Orlando, Florida. Abstract #3052. 10. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 1 Clinical Trials of HGS-ETR2 and HGS-ETR1 in Patients with Advanced Solid Tumors. May 17, 2005. 11. Mita M, et al. A Phase 1, pharmacokinetic (PK) study of HGS-ETR1, an agonistic monoclonal antibody to TRAIL-R1, in patients with advanced solid tumors. 96th Annual Meeting of the American Association for Cancer Research, Anaheim, California, 2005. Abstract #544. 12. Tolcher, et al. A Phase 1 clinical trial HGS-ETR2, a fully human monoclonal antibody to TRAIL-R2 in patients with advanced solid tumors. 96th Annual Meeting of the American Association for Cancer Research, Anaheim, California, 2005. Abstract #543. 13. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 1 Clinical Trial of HGS-ETR1 in Patients with Advanced Solid Tumors. April 18, 2005. 14. Cohen RB, et al. A Phase 1 clinical trial of HGS-ETR1, an agonistic monoclonal antibody to TRAIL-R1, in patients with advanced solid tumors. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Oral Presentation. 15. Hotte SJ, et al. Phase 1 study of a fully human monoclonal antibody to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) in subjects with advanced solid malignancies or non-Hodgkin's lymphoma (NHL). 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #208. 16. (HGSI Press Release) Human Genome Sciences Reports Results of Ongoing Phase 1 Clinical Trials of HGS-ETR1 in Patients with Advanced Cancers. September 29, 2004. 17. Tolcher AW, et al. A phase 1 and pharmacokinetic study of HGS-ETR1, a fully human monoclonal antibody to TRAIL-R1 (TRM-1), in patients with advanced solid tumors. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #3060. 18. Le LH, et al. Phase 1 study of a fully human monoclonal antibody to the tumor necrosis factor-related apoptosis-inducting ligand death receptor 4 (TRAIL-R1) in subjects with advanced solid malignancies or non-Hodgkin's lymphoma. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #2533. 19. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 1 Clinical Trials of HGS-ETR1 (TRAIL-R1 mAb) in Patients with Advanced Cancers. June 7, 2004. 20. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5. Lyon, IARC Press, 2001;1. 21. Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA: A cancer journal for clinicians, 1999;49:33-64. 22. Black RJ, Bray F, Ferlay J, Parkin DM. Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990. Eur J Cancer 1997;33:1075-1107. 23. Jemal A, Tiwari RC, Murray T, et al. Cancer Statistics, 2004. Cancer 2004; 54(1):8-29. 24. Cragg GM. Paclitaxel (Taxol): A success story with valuable lessons for natural product drug discovery and development. Med Res Rev 1998;18:315-331. 25. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Eng J Med 2004;350:2335-2342. 26. Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 2004;22(2):229-237. 27. Goldberg R, Sargent D, Morton R, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004;22(1):23-30. 28. Erbitux, summary of product characteristics, EMEA, Committee for Proprietary Medicinal Products summary of opinion for Erbitux. Mar 2004. CPMP/7618/04 corr. 29. Rothenberg ML, Oza AM, et al. Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil- leucovorin: Interim results of a Phase III Trial. J Clin Oncol 2003;21:2059-2069. 30. Plate S. ESMO minimum clinical recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer. Ann Oncol 2003;12:1053-1054. 31. Kohne CH, Van Cutsem E, Wils J, et al. Irinotecan improves the activity of the AIO regimen in metastatic colorectal cancer: Results of EORTC GI Group study 40986. Proc AmSocClinOncol 2003;22:Abstract 1018. 32. Holen KD, Saltz LB. New therapies, new directions: Advances in the systematic treatment of metastatic colorectal cancer. Lancet Oncol 2001;2:290-297. 33. Vanhoefer U, Harstrick A, Achterrath W, et al. Irinotecan in the treatment of colorectal cancer: Clinical overview. J Clin Oncol 2001;19:1501-1518. 34. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomized trial. Lancet 2000;355:1041-1047. 35. Meta-analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998;16:301-308. 36. University of York NHS Centre for Reviews and Dissemination. The management of colorectal cancer. Effective Health Care 1997;3:76. 37. Cunningham D, Findlay M. The chemotherapy of colon cancer can no longer be ignored. Eur J Cancer 1993;29A:2077-2079. 38. Lokich JJ, Ahlgren JD, Gullo JJ, et al. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: A Mid-Atlantic Oncology Program Study. J Clin Oncol 1989;7:425-432. 39. (HGSI Press Release) GlaxoSmithKline Exercises Option to Human Genome Sciences' TRAIL Receptor Antibody. August 18, 2005. 40. Halpern W, et al. Variable distribution of TRAIL receptor 1 in primary human tumor and normal tissues. 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 2004: Abstract #225. 41. Georgakis GV, et al. Selective agonistic monoclonal antibodies to the TRAIL receptors R1 and R2 induce cell death and potentiate the effect of chemotherapy and bortezomib in primary and cultured lymphoma cells. American Society of Clinical Oncology Annual Meeting, 2004: Abstract #6595. 42. Gillotte D, Zhang Y, Poortman C, et al. Human agonistic anti-TRAIL receptor antibodies, HGS-ETR1 and HGS-ETR2, induce apoptosis in ovarian tumor lines and their activity is enhanced by taxol and carboplatin. Proceedings from the AACR 2004; 73:3579. 43. Younes A, Kadin ME. Emerging applications for the tumor necrosis factor family of ligands and receptors in cancer therapy. J Clin Oncol 2003;21:3526-3534. 44. Humphreys RC, et al. TRAIL R2-mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis inducing ligand receptor 2, affects tumor growth and induces apoptosis in human tumor xenograft models in vivo. 94th AACR Annual Meeting. Abstract 642. 45. Alderson RF, et al. TRAIL-R2 mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis inducing ligand receptor 2, induces apoptosis in human tumor cells. 94th AACR Annual Meeting. Abstract 963. 46. Buchsbaum DJ, Zhou T, Grizzle WE, et al. Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model. Clin Cancer Research 2003; 9:3731-3741. 47. Pukac, Kanakaraj, Alderson, et al. TRAIL-R1 mAb, a human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis- inducing ligand receptor 1, induces apoptosis in human tumor cells in vitro and in vivo. American Association for Cancer Research 94th Annual Meeting. July 2003, Abstract 6429. 48. Ashkenazi A. Targeting death and decoy receptors of the tumor necrosis factor superfamily. Nat Revs Cancer 2002; 2:420-430. 49. Salcedo, Alderson, Basu, et al. TRM-1, a fully human TRAIL-R1 agonistic monoclonal antibody, displays in vitro and in vivo anti- tumor activity. American Association for Cancer Research 93rd Annual Meeting. April 2002, Abstract 4240. 50. Humphreys R, et al. TRAIL-R1 and TRAIL-R2 human agonistic monoclonal antibodies display in vitro and in vivo activity on human cancer cells. Society for Biological Therapy 2002; oral presentation. 51. Chuntharapai A, Dodge K, Grimmer K, et al. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J Immunol 2001; 166:4891-4898. 52. Ichikawa K, Liu W, Zhao L, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 2001; 7:954-960. 53. Ashkenazi A. Apo-2L/TRAIL in Cytokine Reference. Academic Press 2000. 54. Ashkenazi A. et al. Safety and anti-tumor activity of recombinant soluble APO2 ligand. J Clin Inv July 1999; 104(2): 155-162. 55. (HGSI Press Release) Cambridge Antibody Technology and Human Genome Sciences Announce Second Drug Partnership. January 8, 2002.

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