Affymax, Inc. (Nasdaq:AFFY) and Takeda Global Research & Development Center, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE, 4502), today announced preliminary top-line results from the Phase 3 clinical program for the investigational drug, Hematide™/peginesatide, for the treatment of anemia in chronic renal failure patients. The primary efficacy endpoint, the mean change in hemoglobin (Hb) from baseline, in each of the four Phase 3 studies (EMERALD 1, EMERALD 2, PEARL 1 and PEARL 2) met the statistical criteria for non-inferiority, when Hematide was compared to epoetin and darbepoetin, in correcting and/or maintaining Hb in the target range. Hematide also met the statistical criterion for non-inferiority in the combined four studies for the adjudicated cardiovascular composite safety endpoint (CSE), which was composed of death, stroke, myocardial infarction, congestive heart failure, unstable angina, and arrhythmia (hazard ratio (HR) 1.06, 90 percent confidence interval (CI) 0.91 - 1.22). The median duration of follow-up for patients on study drug in the four trials was 1.3 years.
“We are continuing to evaluate the data, in particular the non-dialysis studies, and the impact on the timing of an NDA submission.”
In a subgroup analysis of CSE events in the EMERALD studies in maintenance treatment of anemia in dialysis patients, the frequency of CSE events was balanced between Hematide and the comparator (HR 0.95, 90 percent CI 0.79 - 1.13).
A difference in CSE events was noted, however, when a subgroup analysis was conducted in non-dialysis patients. In the PEARL trials, which evaluated correction and maintenance treatment of anemia in non-dialysis patients, the frequency of CSE events was higher in the Hematide group (21.6 percent) versus the comparator (17.1 percent) (HR 1.34, 90 percent CI 1.03 - 1.73).
The Hematide Phase 3 program, which involved 2,609 randomized patients, consisted of four open-label, randomized active-controlled clinical trials in the U.S. and Europe, including two studies in non-dialysis patients (PEARL 1 and 2) and two others in dialysis patients (EMERALD 1 and 2). In all studies, Hematide was dosed once every four weeks while comparator drugs were dosed more frequently according to their product labels. In these studies, epoetin was dosed one-to three-times per week and darbepoetin was dosed every two weeks. The Hb target range was 11-12 g/dL for non-dialysis patients and 10-12 g/dL for those on dialysis.
"Completion of these four Phase 3 studies is a key milestone and we look forward to pre-NDA discussions with the FDA," said Arlene M. Morris, chief executive officer of Affymax, Inc. "We are continuing to evaluate the data, in particular the non-dialysis studies, and the impact on the timing of an NDA submission."
"The focus of Takeda and Affymax is patients' needs, which are paramount in drug development. Together, we are working to bring this treatment option to patients with chronic renal failure and to physicians who treat them," said Azmi Nabulsi, M.D., M.P.H, president of Takeda Global Research & Development Center.
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