Onyx announces data from three carfilzomib studies on RRMM

Dec 12 2011

Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced summaries of three poster presentations of single-agent carfilzomib, a next generation proteasome inhibitor, in patients with relapsed and/or refractory multiple myeloma at the 53rd American Society of Hematology (ASH) Annual Meeting in San Diego, CA. 

"This expanded data set supports our belief in the potential of carfilzomib to treat late-stage patients with relapsed and refractory multiple myeloma," said Ted W. Love, M.D., Executive Vice President and Head of Research and Development and Technical Operations at Onyx Pharmaceuticals.

Abstract #1877: Multivariate Modeling Reveals Evidence of a Dose-Response Relationship in Phase 2 Studies of Single-Agent CarfilzomibIn an analysis of 430 patients from Phase 2 studies, a highly significant dose-response relationship for carfilzomib was observed across key efficacy endpoints including the primary endpoint of overall response rate (ORR), as well as duration of response (DOR), time to progression (TTP), progression-free survival (PFS) and overall survival (OS). These observations were confirmed and quantified using a statistically rigorous, multivariate analysis. The dose response relationship was also apparent in the magnitude of response (partial response or better) across study participants. While a corresponding dose-toxicity analysis is ongoing, carfilzomib has been shown to have a similar tolerability profile at 20mg/m(2) and 27mg/m(2) doses. These findings are being further assessed in clinical trials evaluating higher dosing regimens.

Abstract #1876: Integrated Safety Data from Phase 2 Studies of Monotherapy Carfilzomib in Patients with Relapsed and Refractory Multiple Myeloma: An Updated Analysis In an analysis of 526 patients, the authors concluded that these data confirm and extend earlier results indicating that single-agent carfilzomib has an acceptable safety profile in heavily pretreated patients with relapsed and refractory multiple myeloma. Carfilzomib was associated with a low rate of typically mild to moderate, non dose-limiting peripheral neuropathy (PN). PN of any grade was reported in 73 patients (14 percent) across the studies, and one patient (<1 percent) discontinued treatment due to a PN-related adverse event. In regard to renal events, less than 1 percent of patients discontinued treatment due to a renal event and 87 percent of patients had no worsening of renal function. Investigator-assessed cardiac events, some of which resulted in death possibly related to carfilzomib (<1 percent) or treatment discontinuation, were reported in this heavily pretreated, late-stage population. Cardiac failure events were reported in 7 percent of patients regardless of causality. Cardiac events resulting in treatment discontinuation included congestive heart failure (2 percent), cardiac arrest (1 percent) and myocardial ischemia (<1 percent). The extent to which cardiac events were due to patients' baseline comorbidities, toxicity from prior treatments, effects of multiple myeloma, carfilzomib itself, or a combination of these factors could not be determined. Rates and causes of death were consistent with those observed in heavily pretreated patients with end-stage multiple myeloma.

Abstract #1875: Unfavorable Cytogenetic Characteristics do not Adversely Impact Response Rates in Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Single-Agent Carfilzomib on the 003-A1 StudyThis analysis evaluated the impact of specific cytogenetic abnormalities on efficacy and treatment outcomes including response rates, time-to-event endpoints, and OS. In patients with multiple myeloma, cytogenetic abnormalities with certain genetic variations have a well-documented but variable adverse impact on therapeutic response and time to event. Of the 229 evaluable patients, 71 patients had unfavorable cytogenetic status. Cytogenetic abnormalities are defined as the presence of del 13 or hypodiploidy by metaphase cytogenetic analysis and/or del 17p13, t(4;14), t (14;16) by fluorescence in situ hybridization (FISH).  An analysis of the results showed that response rates to carfilzomib among patients with normal/favorable cytogenetics were comparable to rates among patients with unfavorable cytogenetic abnormalities.

SOURCE Onyx Pharmaceuticals, Inc.