Here is the first of two major announcements by Onyx Pharmaceuticals concerning their new multiple myeloma drug carfilzomib:
Onyx Pharmaceuticals’ Carfilzomib Continues to Demonstrate Encouraging
Results in Ongoing Phase 2 Multiple Myeloma Study
Fifty-five Percent Single-Agent Response Rate in Relapsed/Refractory Setting
Emeryville, CA – June 5, 2010 – 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-naïve) and those who had received prior bortezomib treatment (bortezomib-treated). Of the 119 bortezomib-naïve 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-naïve 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.”
Phase 2 004 Trial Design
The open-label, single agent ongoing Phase 2 study, known as the 004 study, is being conducted in collaboration with the Multiple Myeloma Research Consortium, and enrolled approximately 150 patients with relapsed and/or refractory multiple myeloma who have received 1-3 prior treatments. Patients include two populations: bortezomib-naïve 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. The primary endpoint is ORR and secondary endpoints include TTP, DOR, overall survival and safety.
About the Carfilzomib Development Program
Carfilzomib is a selective, next-generation proteasome inhibitor that is being investigated in a broad clinical trial program in multiple myeloma.
The pivotal Phase 2b monotherapy study, also known as 003-A1, enrolled patients with relapsed/refractory multiple myeloma. Top-line results, expected in mid-2010, may support the filing of a U.S. New Drug Application (NDA) by year-end 2010.
A Phase 3 clinical trial evaluating the combination of lenalidomide and low dose dexamethasone with or without carfilzomib in patients with relapsed multiple myeloma is expected to begin shortly. The company has an agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) and received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the 009 trial. Carfilzomib is also being evaluated in advanced solid tumors.
A second Phase 3 European clinical trial of carfilzomib is planned in relapsed/refractory myeloma and is designed to support a registrational filing with the EMA. Carfilzomib is also being evaluated in advanced solid tumors.
I will be writing about this and the other Carfilzomib study here and in The Myeloma Beacon through Tuesday. Exciting stuff! Feel good and keep smiling! Pat