Phase 2 study of carfilzomib shows promising results in patients with refractory multiple myeloma

Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced results from an ongoing Phase 2 study, known as the 004 study, of the company's lead proteasome inhibitor, carfilzomib. Results demonstrated promising overall response rates when carfilzomib was administered as a single agent in patients with relapsed and/or refractory multiple myeloma. These data were presented at the 51st annual meeting of the American Society of Hematology (ASH) in New Orleans.

Patients were divided into two populations: 73 evaluable patients with relapsed and/or refractory multiple myeloma who had not received prior bortezomib (Velcade®) treatment, classified as bortezomib-naive patients, and 33 evaluable patients with relapsed and/or refractory disease following bortezomib treatment, classified as bortezomib-treated patients.

Michael Wang, M.D., assistant professor, department of lymphoma and myeloma at the University of Texas M. D. Anderson Cancer Center and co-investigator of the study, reported that the bortezomib-naive patients when treated with carfilzomib achieved an overall response rate (ORR) of 46 percent in 54 evaluable patients at 20 mg/m2 and 53 percent in 19 evaluable patients with dose escalation to 27 mg/m2. Additionally, Dr. Wang reported interim results for secondary endpoints at the 20 mg/m2 dose, including time-to-progression (TTP) of 7.6 months and duration of response (DoR) of 8.4 months.

David Siegel, M.D., Ph.D., division chief of myeloma at the John Theurer Cancer Center and co-investigator of the study, reported that 33 evaluable patients who were previously treated with bortezomib achieved an ORR of 18 percent when administered carfilzomib. Dr. Siegel reported interim results for a secondary endpoint of TTP at 5.3 months and DoR of more than 9 months. More than 20 percent of patients were able to complete the full 12 cycles (48 weeks) of therapy in both studies without cumulative side effects.

"These interim results suggest that carfilzomib could benefit patients with multiple myeloma who are no longer responding to current therapies," said Dr. Siegel. "Additionally, given the low incidence of neuropathy and generally mild and manageable adverse events in this trial, these results suggest that increasing the dosage of carfilzomib up to 27 mg/m2 is well tolerated despite a high degree of coexisting medical conditions, such as renal insufficiency and diabetes."

Overall, treatment with carfilzomib was well tolerated and no unexpected side effects occurred. The most common grade 3 treatment-related adverse events occurred in less than 5 percent of the patients and included fatigue, pneumonia, neutropenia, lymphopenia and anemia. Peripheral neuropathy of any grade was rare and there were no grade 4 adverse events observed.

Other findings from the two populations include:

• Carfilzomib has substantial single-agent activity despite several prior treatments with different combination regimens.
• Carfilzomib was well-tolerated with chronic administration, even in patients with renal insufficiency.
• Patients were able to remain on full-dose therapy for more than 12 cycles.

"These data support our ongoing carfilzomib program in multiple myeloma, a disease that has poor long-term survival, and for which there are no alternative courses of therapy for patients who relapse following treatment or become resistant to currently approved therapies," said Michael Kauffman, M.D., Ph.D., interim chief medical officer at Onyx. "There is a clear need to provide new treatment options to patients with multiple myeloma, and we are working to potentially file a New Drug Application for carfilzomib by the end of 2010."

Trial Design

This open-label, single agent ongoing Phase 2 study is being conducted in collaboration with the Multiple Myeloma Research Consortium, and is designed to enroll approximately 150 patients with relapsed and/or refractory multiple myeloma who have received 1-3 prior treatments. Patients included two populations: bortezomib-naive patients with relapsed and/or refractory multiple myeloma and bortezomib-treated patients with relapsed and/or refractory multiple myeloma. Prior therapies include alkylating agents, stem cell transplant, thalidomide, lenalidomide and anthracyclines, and bortezomib in the bortezomib-treated patients. To date, 73 evaluable bortezomib-naive patients (54 who received 20mg/m2 and 19 who received up to 27mg/m2), and 33 evaluable patients receiving previous treatment with bortezomib have been enrolled. The primary endpoint is overall response rate and secondary endpoints include TTP, DoR, overall survival and safety.