Human Genome Sciences, Inc. (Nasdaq: HGSI) reported initial topline results from an ongoing randomized Phase 2 clinical trial of its TRAIL receptor antibody HGS-ETR1 (mapatumumab) in combination with bortezomib (Velcade) in patients with advanced multiple myeloma. The initial data from the multiple myeloma study show that HGS-ETR1 was well tolerated and suggest that disease response was comparable for this combination vs. bortezomib alone. “We continue to be excited about HGS-ETR1 and our TRAIL receptor antibody program,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “The TRAIL-mediated apoptosis pathway is an important area of cancer research, and agonistic antibodies to this target offer great promise. HGS-ETR1 is the most advanced of any product in development that targets this pathway, with three randomized chemotherapy combination trials currently ongoing to evaluate its potential for the treatment of specific cancers. We look forward to maturing results from all three trials. Taken together, these results will inform our decision on whether to advance HGS- ETR1 to Phase 3 development.” Key Findings The trial in advanced multiple myeloma is a randomized, multi-center, open-label Phase 2 study to evaluate the efficacy and safety of HGS-ETR1 (mapatumumab) in combination with bortezomib in these patients. 104 patients are being treated in the study, which is being conducted in the United States, Canada, Australia and India. Patients were randomized into three treatment groups, with one group receiving bortezomib alone and two groups receiving bortezomib in combination with mapatumumab (10 mg/kg or 20 mg/kg). Approximately 43% (15/35) of the patients in the group receiving bortezomib alone were randomized contemporaneously with randomization of the group receiving a combination of bortezomib and mapatumumab at 10 mg/kg. The remaining 57% (20/35) of the patients in the group receiving bortezomib alone were randomized contemporaneously with randomization of the group receiving a combination of bortezomib and mapatumumab at 20 mg/kg. The primary objective of the study is to evaluate disease response to mapatumumab in combination with bortezomib, versus bortezomib alone, in patients with relapsed or refractory multiple myeloma. Secondary objectives include evaluation of progression-free survival, safety and tolerability, and plasma concentrations of mapatumumab for use in a population pharmacokinetic analysis. Patients participating in the study had received a median of 2 previous cancer treatment regimens. At baseline, 17.1% (6/35) of patients in the treatment group receiving bortezomib alone had Stage 3 disease, vs. 40.6% (13/33) in the group receiving the combination of bortezomib and mapatumumab at 10 mg/kg, and 19.4% (7/36) in the group receiving the combination of bortezomib and mapatumumab at 20 mg/kg. The initial data show that mapatumumab was well tolerated and could be administered safely and repetitively in combination with bortezomib, with no evidence of increased toxicity in patients receiving the combination of bortezomib and mapatumumab, vs. patients receiving bortezomib alone. Overall, based on initial data, disease response was comparable among the three treatment groups, including the following findings: — Three complete responses (8.3%; N=36) were observed among patients in the treatment group receiving the combination of bortezomib and mapatumumab at 20 mg/kg, vs. no complete responses in the group receiving bortezomib alone. — Clinical responses were observed in 51.4% (18/35) of patients in the treatment group receiving bortezomib alone (0 complete and 18 partial). The response rate observed for bortezomib in the current study compares with a response rate identified in the FDA-approved bortezomib label of approximately 38%. — Clinical responses were observed in 50.0% (18/36) of patients in the treatment group receiving the combination of bortezomib and mapatumumab at 20 mg/kg (3 complete and 15 partial). — Clinical responses were observed in 30.3% (10/33) of patients in the treatment group receiving the combination of bortezomib and mapatumumab at 10 mg/kg (0 complete and 10 partial). — Stable disease was observed in approximately a third of the patients on study and was comparable across all treatment groups. The multiple myeloma study is ongoing, and 58 patients in this study have not yet experienced disease progression and continue to be treated and/or followed.