Updated safety data from Phase 2b 003-A1 study of carfilzomib announced

Dec 7 2009

Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced updated safety data from the pivotal Phase 2b 003-A1 study, known as the 003 trial, demonstrating that carfilzomib is well-tolerated in heavily pre-treated relapsed and refractory multiple myeloma patients. These data were presented today at the ASH/ASCO Joint Symposium at the 51st annual meeting of the American Society of Hematology (ASH) in New Orleans. Enrollment in this trial is complete>

"These results show that carfilzomib is well-tolerated and can be administered at a full dose over a long period of time even in a very sick patient population for whom all available treatment options have been exhausted and who have multiple comorbidities," said lead investigator Sundar Jagannath, M.D., chief of the Multiple Myeloma Program, Bone Marrow and Blood Stem Cell Transplantation at St. Vincent's Comprehensive Cancer Center in New York. "We look forward to the full data from this trial next year."

Dr. Jagannath also presented results from the Phase 2 003-A0 study, which recruited patients whose myeloma had relapsed from two or more prior therapies and was refractory to their previous therapy. This study is the lead-in study for the current Phase 2b registrational trial in the same population. Data from this study was initially presented at the American Society for Clinical Oncology (ASCO) annual meeting in June 2009. Patients in the study had a median of five prior therapies. Previously presented efficacy data from 39 evaluable patients in the 003-A0 pilot study included an 18 percent overall response rate (partial response or better) and a 26 percent clinical benefit rate (minor response or better), median time to tumor progression of 5.1 months and a median of 7.4 months response duration.

Based on the emerging safety profile, the 003-A0 protocol was amended in 2008 to permit increased dosing of up to 27 mg/m. The protocol was also expanded into the 003-A1 Phase 2b trial, enrolling 269 patients with relapsed and refractory myeloma and a dose escalation from 20 mg/m to 27 mg/m after one cycle. The primary endpoint for the Phase 2b 003-A1 pivotal study is overall response rate, and secondary endpoints include clinical benefit response, duration of response, progression-free survival, time-to-progression, overall survival and safety.

Dr. Jagannath presented new safety data on 141 patients in the 003-A1 trial, showing that carfilzomib was well tolerated at the 27 mg/m dose. Grade 3/4 hematologic events included anemia (13.5 percent), thrombocytopenia (16.3 percent), neutropenia (3.5 percent), and febrile neutropenia (0.7 percent). The rate of grade 3/4 peripheral neuropathy was 0.7 percent. The regimen was well tolerated with prolonged administration of more than 12 cycles (48 weeks) in approximately 10% of patients, and no clinically significant cumulative toxicities have been noted to date. Both portions of the trial are being conducted in collaboration with the Multiple Myeloma Research Consortium.