Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced interim results from an ongoing Phase 2 study, known as the 004 study. Carfilzomib, a selective, next-generation proteasome inhibitor, demonstrated encouraging overall response rates (ORR), tolerability and durable disease control when administered as a single-agent in patients with relapsed and/or refractory multiple myeloma. In 53 evaluable patients who had not been previously treated with bortezomib (Velcade®), carfilzomib achieved an overall response rate of 55 percent at 27mg/m2. Patients in this group also achieved time-to-progression (TTP) of 11.5 months and duration of response (DOR) of 11.5 months. Forty percent of patients were refractory to their most recent therapy prior to entering the trial. Overall response is defined as a partial response or greater.
These data are being presented today at the 46th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago by Ravi Vij, M.D., Associate Professor, Department of Medicine, Oncology Division, Bone Marrow Transplantation & Leukemia Section at the Washington University School of Medicine.
"Although there are no direct comparative studies, based on historical controls, carfilzomib is exhibiting one of the highest single agent response rates and longest durations of response in patients with multiple myeloma who have had one to three prior therapies in this ongoing Phase 2 study," said Dr. Vij. "The data from this trial support carfilzomib's potential to benefit patients with multiple myeloma who are no longer responding to current therapies."
One hundred fifty-five patients with relapsed and/or refractory multiple myeloma were enrolled in the study and were divided into two populations: patients who had not received prior bortezomib treatment (bortezomib-naive) and those who had received prior bortezomib treatment (bortezomib-treated). Of the 119 bortezomib-naive patients, 53 evaluable patients received carfilzomib at 27mg/m2 and 53 evaluable patients received carfilzomib at 20mg/m2. On the bortezomib-treated arm, 34 evaluable patients received carfilzomib at 20mg/m2 and were not dose escalated.
The 53 evaluable bortezomib-naive patients who received carfilzomib at 20mg/m2 achieved an ORR of 45 percent. Other interim results at the 20mg/m2 included TTP of 8.3 months and DOR of 10.2 months. Forty-nine percent of these patients were refractory to their most recent therapy prior to entering the trial.
The 34 evaluable patients previously treated with bortezomib achieved an ORR of 21 percent when treated with carfilzomib at the 20mg/m2 dose. Secondary endpoints included TTP of 8.1 months and DOR of 11.5 months. Forty-two percent of these patients were refractory to their most recent therapy prior to entering the trial.
In the overall study population, treatment with carfilzomib was well-tolerated, and no new or unexpected adverse events occurred. The most common Grade 3 treatment-emergent adverse events included: pneumonia (11 percent), anemia (9.7 percent), neutropenia (9.7 percent) and thrombocytopenia (9 percent). Peripheral neuropathy of any grade was infrequent and no Grade 4 adverse events were observed.
"This data from the 004 study will be included in the planned U.S. New Drug Application (NDA) that we intend to file by year-end 2010, pending top-line data from the ongoing registration trial, known as the 003-A1 study. The results from 003-A1, a Phase 2b trial, will form the basis for the NDA, which we expect to file under the accelerated approval mechanism," stated Michael Kauffman, M.D., Ph.D., Chief Medical Officer at Onyx. "In addition, we have announced our intention to initiate an international Phase 3 clinical trial evaluating carfilzomib in combination with lenalidomide and low dose dexamethasone in earlier stage myeloma. This trial is being conducted through a Special Protocol Assessment with the U.S. Food and Drug Administration and with Scientific Advice from the European Medicines Agency."
Onyx Pharmaceuticals, Inc.