Affymax, Inc., a biopharmaceutical company, and Takeda Pharmaceuticals USA, Inc., a subsidiary of Japan-based Takeda Pharmaceutical Company Limited, have announced the post-hoc sub-group analyses of the EMERALD Phase III studies that evaluated OMONTYS Injection, an erythropoiesis-stimulating agent, or ESA, for the treatment of anemia due to chronic kidney disease, or CKD, in adult dialysis patients.
In these exploratory post-hoc analyses, investigators pooled data on IV iron dose, along with measures of iron deficiency - serum ferritin and transferrin saturation (TSAT), from US patients enrolled in the EMERALD 1 and 2 studies (approximately 80 % of study population).
In the full analysis population (randomized patients receiving greater than or equal to 1 study drug dose; n=853 OMONTYS, n=436 epoetin) over a 60-week period, patients in the OMONTYS group received an average of 148.8 mg of IV iron per month and patients in the epoetin group received 168.5 mg per month.
In the completer population (greater than or equal to 60 weeks' drug exposure; ferritin, TSAT measured at same visit; n=604 OMONTYS; n=336 epoetin), patients in the OMONTYS group received an average of 152.9 mg per month and patients in the epoetin group received an average of 171.8 mg per month. TSAT at baseline was 30.2% and 29.4% in the OMONTYS and epoetin groups, respectively. Beginning at the first time point (week 12), TSAT for the full analysis population was 37.9% and 30.7% for OMONTYS and epoetin, respectively, and TSAT for the completer analysis population was 37.9% and 30.9% for OMONTYS and epoetin, respectively.
Serum ferritin levels at baseline were 686 ng/mL and 674 ng/mL in the OMONTYS and epoetin groups, respectively. At week 60, serum ferritin levels for the full analysis population were 742 ng/mL and 768 ng/mL in the OMONTYS and epoetin groups, respectively, and serum ferritin levels for the completer analysis population were 733 ng/mL and 752 ng/mL in the OMONTYS and epoetin groups, respectively. The clinical significance of these analyses is unknown.
Evaluating approximately 1,600 dialysis patients across 172 sites in the US and Europe, the primary efficacy endpoint of the EMERALD 1 and 2 studies was a mean change in Hb between the baseline and evaluation period (between weeks 29 through 36) following study entry.
In these trials, CKD patients on dialysis who were stable on epoetin were randomized to receive OMONTYS either once monthly or to continue treatment with epoetin (according to its labeling), with dose adjustments to maintain Hb levels within the study-specified range (between 10.0-12.0 g/dL). Current Prescribing Information recommends reducing or interrupting the dose as Hb levels approach or exceed 11 g/dL.
The EMERALD studies were part of the first Phase III program to prospectively evaluate the cardiovascular (CV) safety of different ESAs based on a composite cardiovascular safety endpoint (CSE). The CSE was adjudicated by a blinded and independent committee.
"Anemia management is multi-faceted and given the interdependence of irons and ESAs in red blood cell production, it's important to evaluate utilization of these agents in dialysis patients who are being treated for the condition," said Robert Provenzano, chair, division of nephrology, St. John Hospital & Medical Center, Detroit, and presenter of these EMERALD analyses. "The observations of these post-hoc analyses from the EMERALD studies may warrant further scientific evaluation."