ROCKVILLE, Md., Dec. 12 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. announced today that the results of a Phase 2 clinical trial (1-3) demonstrate that HGS-ETR1 (mapatumumab) is well tolerated and capable of producing clinical responses when administered as monotherapy in patients with advanced non-Hodgkin’s lymphoma. The results were presented today in Atlanta at the 47th Annual Meeting of the American Society of Hematology.(4)
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The Phase 2 clinical trial is a multi-center, open-label study to evaluate the efficacy, safety and tolerability of HGS-ETR1, an agonistic human monoclonal antibody to TRAIL receptor 1, in patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). The 40 patients enrolled in the trial received up to six cycles of treatment in the absence of disease progression, with HGS-ETR1 administered as an intravenous infusion once every 21 days. Patients were enrolled into two treatment groups, with 8 patients receiving HGS-ETR1 doses of 3 mg/kg and with 32 patients receiving HGS-ETR1 doses of 10 mg/kg. The objectives of the study are to evaluate disease activity and tumor response to HGS-ETR1 in patients with advanced non- Hodgkin’s lymphoma, to evaluate the safety and tolerability of HGS-ETR1, and to determine plasma concentrations of HGS-ETR1 for use in a population pharmacokinetic analysis. Patients participating in the study were heavily pretreated, having received up to 12 previous cancer treatment regimens, with 69% (28/40) having received 3 or more prior regimens. Of note, 94% (34/36) of the subjects with B-cell NHL had received prior rituximab therapy.
Data made available in an oral presentation (4) showed that HGS-ETR1 is well tolerated, with minimal toxicity, can safely be administered intravenously every 21 days at doses up to 10 mg/kg, and exhibits clinical activity in patients with relapsed or refractory NHL. Clinical responses (1 complete response and 2 partial responses) were observed in three patients (8%, n=40), all of whom had been diagnosed with follicular lymphomas. In addition, stable disease was observed in 30% (12/40) of the patients. To date, 7 patients (18%, n=40) remain without progression of disease, with stable disease or response enduring 9-18 months. Two patients received special permission to continue treatment until progression; one of these patients received 12 cycles of treatment, while the other received 9+ cycles. Follicular lymphomas are of particular interest since the 3 clinical responses were observed in patients with follicular lymphomas. Of the patients enrolled, 43% (17/40) had been diagnosed as having follicular lymphomas. Clinical responses (1 complete response and 2 partial responses, as noted above) were observed in 3/17 (18%) patients with follicular lymphomas, and 11/17 (65%) exhibited either response or stable disease. Images and data from one patient with a partial response were presented and indicated a 75% tumor regression. This patient has received 9 cycles of treatment to date (10 mg/kg), and the tumor in this patient continues to decrease in size.
Anas Younes, M.D., Professor, Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, said, “The Phase 2 results presented today demonstrate that HGS-ETR1 has activity in heavily pretreated patients with relapsed or refractory non-Hodgkin’s lymphoma. These clinical results build on a growing body of preclinical evidence that HGS-ETR1 can induce cell death in a wide variety of cultured lymphoma and leukemia patient samples and cultured cell lines.(5-11) The preclinical data, now supported by emerging clinical observation (2-4), (12-19), suggest that HGS-ETR1 has potential therapeutic value in lymphoid malignancies. The preclinical data also demonstrate that HGS-ETR1 enhances the tumor-killing activity of bortezomib and doxorubicin.(2) Further study of HGS-ETR1 in lymphomas and leukemias is warranted, in combination with agents active in lymphoma.”
A poster presentation, entitled “In Vitro Synergistic Anti-Tumor Activity by Targeting TRAIL-R1 and CD20 Antigen by Combining HGS-ETR1 (Agonistic Human Monoclonal Antibody to TRAIL Receptor 1) and Rituximab Monoclonal Antibody Against Non-Hodgkin’s Lymphoma Cells,” presented the results of preclinical studies designed to determine the biological effects of rituximab when combined with either HGS-ETR1 or HGS-ETR2 in a panel of non-Hodgkin’s lymphoma (NHL) cell lines.(5) Data presented from in vitro studies demonstrate that the inhibition of NHL cell growth by HGS-ETR1 was greater than that achieved by HGS-ETR2 or rituximab alone in the cell lines tested. HGS-ETR1 (and to a much lesser degree, HGS-ETR2) was shown to be capable of inducing apoptosis, antibody-dependent cellular cytotoxicity and complement- mediated cytotoxicity in sensitive B-cell lymphoma cell lines. Data from in vivo animal studies suggest that rituximab in combination with HGS-ETR1 is the most effective in controlling lymphoma growth and improving survival as compared to single-agent rituximab, HGS-ETR2, or rituximab in combination with HGS-ETR2.
Myron S. Czuczman, M.D., a co-investigator for the Phase 2 study of HGS- ETR1 in NHL, and Head, Lymphoma/Myeloma Service, Roswell Park Cancer Institute (Buffalo, NY), said, “The in vitro data that we presented here at the ASH annual meeting show that the combination of HGS-ETR1 and rituximab resulted in significant augmented activity, including significant inhibition of cell proliferation, when compared to either HGS-ETR1 or rituximab alone. These data support further clinical evaluation of HGS-ETR1 in combination with rituximab in patients with B-cell lymphoma.”
David C. Stump, M.D., Executive Vice President, Drug Development, said, “The results of the Phase 2 study of HGS-ETR1 in patients with advanced non- Hodgkin’s lymphoma show that HGS-ETR1 is well tolerated and shows signs of clinical activity in these patients. The responses observed in three patients and the stable disease observed in 30% of the patients who participated in this study are encouraging. These data, combined with other clinical and preclinical results to date support the continued study of HGS-ETR1 in combination with other agents, including rituximab, in patients with non- Hodgkin’s lymphoma.”
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 tumors. Human Genome Sciences took the approach of developing a human monoclonal antibody that would bind the receptor and stimulate the 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) triggers it, but with the advantage of a longer half-life and an exclusive specificity for TRAIL receptor 1.(20-23) The TRAIL receptor-1 agonistic human monoclonal antibody, HGS-ETR1, was made in a collaboration between Human Genome Sciences and Cambridge Antibody Technology.(24)
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 HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, http://www.hgsi.com/products/request.html, or by calling (240) 314-4400, 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. (HGSI Press Release) Human Genome Sciences Completes Patient Enrollment in a Phase 2 Clinical Trial of HGS-ETR1 for the Treatment of Non-Hodgkin’s Lymphoma. March 3, 2005. 2. 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. 3. (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. 4. Younes A, Vose J, Zelenetz AD, Czuczman MS, et al. Results of a Phase 2 trial of HGS-ETR1 (agonistic human monoclonal antibody to TRAIL receptor 1) in subjects with relapsed/refractory non-Hodgkin’s lymphoma (NHL) (ETR1-HM01). 47th Annual Meeting of the American Society of Hematology, 2005. 5. Czuczman MS, Maddipatla S, Knight J, et al. In vitro synergistic anti-tumor activity by targeting TRAIL-R1 and CD20 antigen by combining HGS-ETR1 (agonistic human monoclonal antibody to TRAIL receptor 1) and rituximab monoclonal antibody against non-Hodgkin’s lymphoma cells. 47th Annual Meeting of the American Society of Hematology, 2005. 6. Humphreys, RC. Development and evaluation of cancer therapeutic agents targeting TRAIL receptor 1 and 2. Cancer Drug Discovery and Development: The Oncogenomics Handbook (Ed.: La Rochelle WJ and Shimkets RA, Humana Press, 2005). 7. 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. 8. Georgakis GV, Li Y, Humphreys R, et al. Activity of selective agonistic antibodies to TRAIL death receptors R1 and R2 in primary and cultured tumor cells of hematologic origin. Blood 2003;102:228a (abstract #799). 9. Johnson RL, Huang X, Fiscella M. Human agonistic anti-TRAIL antibodies, HGS-ETR1 and HGS-ETR2, induce apoptosis in diverse hematological tumor lines. Blood 2003;102:981a (abstract #3316). 10. 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. 11. (HGSI Press Release) Human Genome Sciences Reports Results of Preclinical Studies of TRAIL-R1 and TRAIL-R2 Agonistic Human Monoclonal Antibodies at EORTC-NCI-AACR Symposium. October 1, 2004. 12. 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. 13. 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. 14. (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. 15. (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. 16. 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. 17. (HGSI Press Release) Human Genome Sciences Reports Results of Phase 2 Clinical Trial of HGS-ETR1 in Patients with Advanced Colorectal Cancer. November 1, 2005. 18. 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. 19. (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. 20. 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. 21. Pukac L, Kanakaraj P, Alderson R, 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. 22. Salcedo, Alderson R, 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. 23. 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. 24. (HGSI Press Release) Cambridge Antibody Technology and Human Genome Sciences Announce Second Drug Partnership. January 8, 2002.
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CONTACT: Jerry Parrott, Vice President, Corporate Communications,+1-301-315-2777, or Kate de Santis, Director, Investor Relations,+1-301-251-6003, both of Human Genome Sciences, Inc.
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