Onyx Pharmaceuticals announced yesterday the results of an ongoing Phase 2b trial of single-agent carfilzomib ^[1] (Kyprolis ^[2]) for heavily pre-treated re­lapsed and refractory multiple myeloma patients. The over­all response rate after 12 cycles of single-agent car­filz­o­mib treat­ment in this trial was 24 per­cent, and the median duration of response was 7.4 months.

According to Dr. Michael Kauffman, Chief Medical Officer of Onyx Pharmaceuticals, the com­pany’s newly released results dem­onstrate the potential for car­filz­o­mib to significantly improve the outlook for re­lapsed and refractory multiple myeloma patients.

He cited a recent study ^[3] conducted by the Inter­na­tional Myeloma Work­ing Group indicating that patients similar to those enrolled in this Phase 2 trial generally have an 11 per­cent chance of responding to further treat­ment and are predicted to survive for six to ten months.

Onyx Pharmaceuticals may file a new drug application for accelerated approval of car­filz­o­mib by the end of the year.

Carfilzomib is a new drug cur­rently being in­ves­ti­gated as a potential multiple myeloma ther­apy. Similar to Velcade ^[4] (bor­tez­o­mib), it is a proteasome inhibitor that prevents the growth and spread of myeloma cells by interrupting their protein-related cellular processes. However, car­filz­o­mib triggers this response by binding to different proteins than those bound by Velcade.

The Phase 2 trial included 266 re­lapsed and refractory patients who had received a median of five prior ther­a­pies. They were treated with 20 mg/m² of car­filz­o­mib during the first treat­ment cycle. The dose was increased to 27 mg/m² during sub­se­quent treat­ment cycles, and the maximum number of treat­ment cycles admin­istered was 12.

Of the 266 study participants, 36 per­cent showed a minimal response or greater, and 24 per­cent achieved a partial response or better.

Carfilzomib was well tolerated, and the researchers did not observe any unexpected side effects.  Common side effects asso­ci­ated with car­filz­o­mib include low blood cell counts, fatigue, nausea, shortness of breath, and diarrhea.

The full trial results will be presented at the American Society of Hematology meeting in Orlando in December.

The results of this study echo the positive data from a smaller-scale study presented at the American Society of Clinical Oncology Annual Meeting in early June. In that study, re­lapsed and refractory myeloma patients, including those who were Velcade-resistant, exhibited positive responses to single-agent car­filz­o­mib treat­ment (see related Beacon ^[5] news).

In comparison, results from a small Phase 2 trial ^[6] showed that 26 per­cent of heavily pre-treated multiple myeloma patients responded to pomalidomide ^[7] (Pomalyst ^[8]) plus dexamethasone ^[9] (Decadron), with an addi­tional 28 per­cent achieving a minor response.  These trials indicated that both car­filz­o­mib and poma­lido­mide hold promise for the treat­ment of re­lapsed and refractory myeloma patients.

Onyx Pharmaceuticals recently launched a Phase 3 trial evaluating the com­bi­na­tion of Revlimid ^[10] (lena­lido­mide) and low-dose dexa­meth­a­sone with and without car­filz­o­mib to further in­ves­ti­gate car­filz­o­mib’s potential in re­lapsed and refractory multiple myeloma patients.

For more in­­for­ma­tion, please refer to the Onyx Pharmaceuticals press release ^[11].