Takeda, Affymax announce additional peginesatide Phase 3 study results in dialysis patients

Affymax, Inc. (Nasdaq: AFFY) and Takeda Pharmaceutical Company Limited (TSE:4502, "Takeda"), today announced results of additional analyses from two Phase 3 studies (EMERALD 1 and 2) of the investigational agent, peginesatide (formerly known as Hematide™) in chronic renal failure (CRF) patients on dialysis with anemia. Building on the primary analysis of the EMERALD studies, which showed that once-monthly peginesatide was comparable to epoetin given up to 13 times a month in maintaining hemoglobin (Hb) levels with a generally similar adverse event rate, these data provide additional information on the maintenance of Hb within treatment targets over time (up to 100 weeks), as well as cardiovascular safety results of this once-monthly agent in the dialysis patients studied. These data, along with a demographic analysis from the dialysis studies, were part of three poster presentations at the National Kidney Foundation's (NKF) Spring Clinical Meetings in Las Vegas, Nevada.

Peginesatide is in development for the treatment of anemia in CRF patients on dialysis. The EMERALD studies were part of the largest Phase 3 clinical program to support initial registration of an erythropoiesis stimulating agent (ESA) in the treatment of anemia in CRF. The trials evaluated the efficacy and safety of peginesatide administered once-monthly, compared to epoetin alfa or epoetin beta dosed up to 13 times a month, in maintaining Hb levels within the current recommended target range (between 10-12 g/dL), a goal of anemia management. Epoetin alfa or beta were dosed according to their product labels. Dialysis patients randomized to the peginesatide arm were switched from epoetin alfa or epoetin beta to peginesatide.

"The Phase 3 EMERALD program was particularly interesting because the studies evaluated the efficacy and safety of peginesatide in patients who were stable on an epoetin dose and then switched to peginesatide," said Anne-Marie Duliege, M.D., chief medical officer, Affymax. "We look forward to submitting our New Drug Application and reviewing our findings with the FDA."

"Evaluating cardiovascular safety is important in patients receiving dialysis because they typically have several co-existing conditions, such as diabetes and heart disease," said Darryl Sleep, M.D., vice president, Clinical Science, Takeda Global Research & Development Center Inc., a wholly-owned subsidiary of Takeda. "The EMERALD trials were the first Phase 3 registration studies to prospectively evaluate the cardiovascular safety of an erythropoiesis stimulating agent through an adjudicated composite safety analysis. We believe our results provide important information on anemia treatment in this population."

Safety and Efficacy of Peginesatide for Treatment of Anemia in Hemodialysis Patients Previously on Epoetin Alfa or Epoetin Beta (Poster #s 217 and 63), April 27, 2011

The peginesatide data presented at NKF were from two Phase 3 clinical trials known as EMERALD 1 and EMERALD 2. The primary efficacy endpoint for both studies was the comparison of the mean change in Hb levels from baseline to the evaluation period across both treatment groups. In both Phase 3 trials, peginesatide had similar results to epoetin in maintaining Hb levels within target range. Specific study results presented at the meeting based on key secondary analyses are as follows:

• EMERALD 1: The percentage of patients whose Hb levels remained within the target range during four-week periods in the initial titration period (weeks 1-28) was 60 to 69 percent in patients who were switched to peginesatide and 65 to 74 percent in those who were maintained on epoetin. Hb levels during four-week periods in the evaluation and long-term follow up periods (weeks 29-52) were maintained in 67 to 75 percent of peginesatide patients and 68 to 75 percent of epoetin patients. In this study, Hb levels were maintained without increasing the need for red blood cell transfusions (10 percent in the peginesatide group versus 9 percent in the epoetin group).
• The overall adverse event profile of peginesatide was consistent with that of epoetin and the most commonly reported adverse events in the peginesatide and epoetin arms were diarrhea (20 percent versus 14 percent), cough (19 percent versus 20 percent), dyspnea (19 percent versus 20 percent) and nausea (17 percent versus 19 percent).
• A similar frequency of serious adverse events was observed across groups. Further, a similar frequency of the following cardiovascular events was reported in both treatment groups: death (11.1 percent versus 11.2 percent), stroke (2.3 percent versus 4.5 percent), myocardial infarction (4.8 percent versus 5.9 percent), unstable angina (2.7 percent versus 2.6 percent), congestive heart failure (11.3 percent versus 9.7 percent) and arrhythmia (6.9 percent versus 6.7 percent).
• EMERALD 2: In this trial, 58 to 68 percent of patients switched to peginesatide were within Hb target range during four-week periods in weeks 1-28, compared to 67 to 78 percent who were maintained on epoetin. The number of patients within target range during four-week periods in the evaluation and long-term follow up periods (weeks 29-52) was comparable between treatment groups, with 64 to 70 percent of peginesatide patients within range, versus 65 to 74 percent of those in the epoetin arm. The proportion of patients who received a red blood cell transfusion was similar between peginesatide and the epoetin control (8 percent versus 10 percent).
• The overall adverse event profile of peginesatide was consistent with that of epoetin and the most commonly reported adverse events in the peginesatide and epoetin arms were muscle spasm (20 percent versus 19 percent), dyspnea (18 percent versus 18 percent), nausea (18 percent versus 20 percent) and diarrhea (17 percent versus 18 percent).
• A similar frequency of serious adverse events was observed across groups. Also, a similar frequency of the following cardiovascular events was reported in both treatment groups: death (10.5 percent versus 12.5 percent), stroke (2.6 percent versus 2.9 percent), myocardial infarction (4.4 percent versus 4.8 percent), unstable angina (1.8 percent versus 1.8 percent), congestive heart failure (8.1 percent versus 8.4 percent) and arrhythmia (5.0 percent versus 6.2 percent).

Peginesatide Phase 3 Trial Subjects vs. a Random Sample of U.S. Hemodialysis Patients (Poster #163) - April 27, 2011

In addition to the safety and efficacy data, a demographic comparison presented at NKF showed that U.S. patients included in the EMERALD trials had baseline characteristics that are consistent with patients from a random sample of the U.S. adult hemodialysis population>3 Age, severity of chronic kidney disease and medical history of patients in the trials were generally reflective of the real-world population, as captured through Medicare claims data.