Affymax, Inc. and Takeda Global Research & Development Center, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, announced preliminary top-line results from the phase 3 clinical programme for the investigational drug, Hematide/peginesatide, for the treatment of anaemia in chronic renal failure patients.
The primary efficacy endpoint, the mean change in haemoglobin (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.
In a subgroup analysis of CSE events in the EMERALD studies in maintenance treatment of anaemia 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 anaemia 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 programme, which involved 2,609 randomized patients, consisted of four open-label, randomized active-controlled clinical trials in the US 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.
In the EMERALD studies, patients were randomized two to one to receive Hematide or epoetin. The starting dose of Hematide was based on a conversion from the prior epoetin dose.
The primary efficacy endpoint of these two studies was a mean change in Hb between baseline and the evaluation period, which was between weeks 29 and 36 following entry into the study. This endpoint was met in both studies. The secondary endpoints of the two studies were the proportion of patients who received red blood cell (RBC) transfusions and the proportion of patients who maintained Hb within the target range during the evaluation period.
Hematide is a novel investigational synthetic, PEGylated peptidic compound that binds to and activates the erythropoietin receptor and thus acts as an ESA.
Affymax and Takeda are collaborating on the development of Hematide and plan to co-commercialize the product once approved in the United States. phase 3 clinical trials investigated the potential for Hematide to treat anaemia associated with chronic renal failure. The product, upon approval, will be commercialized outside the United States (in the European Union and Japan) by Takeda.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine.
Affymax, Inc. is a biopharmaceutical company committed to developing novel drugs to improve the treatment of serious and often life-threatening conditions.