Onyx Pharmaceuticals reports positive Phase 2b 003-A1 study results of carfilzomib for refractory multiple myeloma

Dec 7 2010

Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced positive complete results from the Phase 2b 003-A1 study of single-agent carfilzomib, a next generation proteasome inhibitor, in patients with relapsed and refractory multiple myeloma. Carfilzomib achieved an overall response rate (ORR) (partial response or greater) of 24.1 percent and a median duration of response (DOR) of 8.3 months in patients who entered the study after receiving a median of five prior lines of therapy (corresponding to a median of 13 anti-myeloma agents) and whose disease was refractory to their last therapeutic regimen. In addition, patients enrolled in the study had progressive disease upon entering the trial.  The clinical benefit rate (CBR) (minimal response or greater) in the study population was 34.2 percent.  The median overall survival (OS) was 15.5 months. Overall survival for responding patients (greater than or equal to minimal response) has not yet been reached; however, based on current data is expected to exceed 19 months.

Seventy-seven percent of patients had grade 1/2 peripheral neuropathy (PN) upon entry into the study.  New or worsening of PN was uncommon and Grade 3 PN occurred in less than 1 percent of patients. There were no Grade 4 PN events. A subset analysis of patients with PN>

These data are being presented today at the 52nd American Society of Hematology Annual Meeting in Orlando by David Siegel, M.D., Ph.D., Division Chief for Myeloma at John Theurer Cancer Center at Hackensack University Medical Center. The results will also be included in the 2011 Highlights of ASH meetings, taking place January through April.

"There is a significant need for new treatment options for these patients with refractory multiple myeloma who have exhausted all other options," said Dr. Siegel. "This heavily pretreated patient population has received all classes of approved and commonly used myeloma therapies, and the durable responses and tolerability demonstrate carfilzomib's potential as a promising treatment."

In the overall study population, no new or unexpected toxicities were observed. The most common Grade 3/4 adverse events were thrombocytopenia (27 percent), anemia (22 percent), lymphopenia (18 percent), and neutropenia (10 percent).

In a subset analysis of patients who were refractory to bortezomib in their last line of therapy>

"We believe that carfilzomib has the potential to be an important new treatment option for patients with relapsed and refractory myeloma," said Michael G. Kauffman, M.D., Ph.D., Chief Medical Officer of Onyx Pharmaceuticals. "We are particularly encouraged by the activity and very low rates of peripheral neuropathy observed in this study."

Two hundred and sixty-six patients with relapsed and refractory multiple myeloma were enrolled in the study, and 257 patients were evaluable for response. The primary endpoint was ORR. Secondary endpoints included CBR, DOR, OS, time to progression (TTP), progression free survival (PFS), and safety.