Philadelphia, Pa., November 11, 2011, – Affymax, Inc. (Nasdaq: AFFY) and Takeda Global Research & Development Center, Inc., U.S., today announced results from additional analyses of the EMERALD Phase 3 studies that evaluated the investigational agent peginesatide in dialysis patients with anemia due to chronic kidney disease (CKD). The findings, presented at the American Society of Nephrology’s (ASN) Kidney Week, provide further detail on the frequency of adverse events of peginesatide and epoetin alfa or beta, as well as information on the relationship between peginesatide and epoetin doses in the dialysis patients studied, dose requirements of intravenous (IV) and subcutaneous (SC) peginesatide in patients in the United States (US) and European Union (EU) and hemoglobin (Hb) stability. The companies also presented findings on the rate of Hb decline associated with peginesatide and epoetin following dose discontinuation seen in these studies.
“The peginesatide Phase 3 program was one of the most comprehensive clinical programs to support the initial submission of a new drug application (NDA) for an erythropoiesis stimulating agent (ESA),” said Anne-Marie Duliege, M.D., chief medical officer, Affymax. “We believe these data analyses continue to support peginesatide as a potential agent to treat anemia in the dialysis patient population if approved.”
Peginesatide is a synthetic, PEGylated peptidic compound that binds to and stimulates the erythropoietin receptor and thus acts as an ESA. In addition to being the largest Phase 3 clinical program to support the initial NDA submission of an ESA in the treatment of anemia in CKD, the peginesatide Phase 3 studies were also the first to prospectively evaluate the cardiovascular safety of an ESA via an analysis of independently adjudicated cardiovascular events. Peginesatide is currently under review by the US Food and Drug Administration (FDA) and the NDA will be discussed during the Oncology Drugs Advisory Committee hearing on Wednesday, December 7.
“Anemia can severely undermine the health of patients who often suffer from multiple medical conditions in addition to chronic kidney disease,” said Darryl Sleep, M.D., vice president, Clinical Operations, Takeda Global Research & Development Center, Inc., U.S., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited, headquartered in Japan. “Affymax and Takeda are dedicated to addressing medical needs and we look forward to working with the U.S. FDA as they evaluate this potential new option for the treatment of anemia in dialysis patients and the providers involved in their care.”
About the Data Presented at ASN
The data presented at ASN were from the Phase 3 trials known as EMERALD 1 and 2. The two studies 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 target range of 10-12 g/dL. 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 EMERALD findings demonstrated once-monthly peginesatide and epoetin maintained Hb levels in CKD patients on dialysis with anemia with the most common adverse events being diarrhea, cough, dyspnea, nausea and muscle spasm.
Specific findings based on additional analyses presented at the meeting are as follows:
Safety Results From Two Phase 3 Studies of Peginesatide Treatment For Anemia in Hemodialysis Patients (Poster Board # FR-PO1571) – November 11, 2011
An analysis of adverse events including those associated with the ESA drug class (epoetin alfa and beta) was presented at ASN. Pooled patients in each treatment group (1,066 peginesatide; 542 epoetin) had similar demographics, comorbidities and cardiovascular risk factors at the start of the studies. In this evaluation, investigators found once-monthly peginesatide, and epoetin, had the following adverse event rates respectively:
The adjusted on-study mortality rate, which included all deaths that occurred through study discontinuation, was 8.7 deaths per 100 patient follow-up years in the peginesatide group and 9.5 deaths per 100 patient follow-up years in the epoetin group. “Patient years” measures the time all patients actually spent in the study or in follow up; the number of deaths is divided by the total patient years to determine the rate.
Relationship Between Peginesatide and Epoetin Doses in Hemodialysis (HD) Patients (Poster Board # FR-PO1579 ) – November 11, 2011
This retrospective analysis from the EMERALD trials evaluated the dosing relationship between epoetin and peginesatide in dialysis patients who were previously stable on epoetin. Investigators evaluated the dose of epoetin used at study initiation (baseline) and the dose of either epoetin or peginesatide that was administered during the evaluation periods. For people who received the lowest dose of epoetin at baseline (4800U or less), the ratio of units of epoetin versus milligrams of peginesatide needed to keep Hb within range was approximately 1000 to 1. For people who received the highest dose of epoetin at baseline (16,400U or more), the ratio of units of epoetin versus milligrams of peginesatide was approximately 2000 to 1. The investigators noted that for patients receiving high epoetin doses at baseline, the relative dose of peginesatide was less than half that for those receiving low epoetin doses at baseline.
IV Versus SC ESA Dosing Requirements in U.S. and non-U.S. Hemodialysis Patients
(Poster # FR-PO1601) – November 11, 2011
Another EMERALD analysis comparing the dosing requirements based on two routes of administration – IV and SC – was presented at ASN. Results were as follows:
Hemoglobin Stability During Peginesatide Versus Epoetin Treatment in Hemodialysis Patients (Poster # FR-PO1607) – November 11, 2011
In this analysis, EMERALD study investigators reviewed the frequency of Hb variability and dose adjustments in people who were switched to treatment with peginesatide, as well as those who remained on epoetin treatment in both studies. The study protocol specified that for both the peginesatide and epoetin groups dose adjustments should not be made more frequently than every four weeks, unless otherwise required for safety considerations.
According to the results, Hb variability based on the standard deviation was 0.51 and 0.48 respectively; the median absolute deviation-based Hb variability was 0.44 for both treatment groups. Further, the analysis showed dose adjustments (i.e., a change of more than 20 percent from the previous dose) for people receiving peginesatide, compared to those on epoetin was 47 percent vs. 68 percent. The frequency of dose increases and decreases (³1) for peginesatide was 28 and 21 percent, respectively and 55 percent and 53 percent for epoetin.
Rate of Hemoglobin Decline Following Peginesatide Dose Interruption (Poster # FR-PO1570) – November 11, 2011
This analysis, which included 210 of the 1,066 patients switched to peginesatide and 327 of the 542 patients on epoetin, assessed the rate of Hb decline following dose interruption due to elevated Hb levels (≥13.0 g/dL for peginesatide and ≥12.5 g/dL for epoetin). The findings of this analysis showed that the rates of Hb decline following dose interruption for peginesatide and epoetin were as follows: -0.35 g/dL/week for peginesatide and -0.40 g/dL/week for epoetin. The mean time from dose interruption until resumed dosing was approximately three weeks for both groups.
About the EMERALD Studies and the Peginesatide Phase 3 Program
The EMERALD trials were open-label, randomized active-controlled Phase 3 clinical studies that involved over 1,600 dialysis patients. EMERALD 1 included 803 U.S. dialysis patients who were receiving hemodialysis (≥3 months) and were being treated with intravenous (IV) epoetin alfa (≥8 weeks). In this trial, patients were randomized to receive once-monthly peginesatide or epoetin alfa one-to-three times a week. EMERALD 2 enrolled 823 U.S. and EU dialysis patients who were receiving hemodialysis (≥3 months) and were being treated with IV or subcutaneous (SC) injection of epoetin alfa or beta (≥8 weeks). EMERALD 2 patients were randomized to receive once-monthly peginesatide (by IV or SC administration) or epoetin one-to-three times a week.
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.
Affymax and Takeda are collaborating on the development of peginesatide and plan to co-commercialize the product if approved in the U.S. The Phase 3 clinical trials were designed to investigate the potential for peginesatide to treat anemia associated with CKD. If approved, peginesatide could be the first once-monthly ESA marketed for the treatment of anemia associated with CKD patients on dialysis in the United States.
About Anemia in Chronic Kidney Disease on Dialysis
Anemia is a common complication in CKD that impacts the overall health and well-being of CKD patients and is associated with increased rates of hospitalization and mortality.[i],[ii] ESAs are medications commonly prescribed to treat anemia and stimulate red blood cell production.[iii] According to the Center for Medicaid Services (CMS), nearly 95 percent of patients on dialysis in the U.S. are currently receiving ESA treatment for anemia in CKD.[iv] Research has shown that there may be challenges with anemia management due to factors such as, Hb variability and stability, among other concerns.[v]
About Affymax, Inc.
Affymax, Inc. is a biopharmaceutical company committed to developing novel drugs to improve the treatment of serious and often life-threatening conditions. For additional information, please visit www.affymax.com.
This release contains forward-looking statements, including statements regarding the continuation and success of Affymax's collaboration with Takeda, milestones expected to be accomplished, timing, design and progress of the peginesatide development program and the timing and potential regulatory approval and commercialization of peginesatide. Affymax's actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties, including risks relating to the approvability and completeness of the New Drug Application (NDA) filing, risks relating to regulatory requirements and approvals, in particular the FDA's interpretation and review of the data in the NDA including issues related to the subgroup analyses in non-dialysis, data quality and integrity particularly in non-inferiority designed trials, the continued safety and efficacy of peginesatide in clinical development, the timing of patient accrual in ongoing and planned clinical studies, research and development efforts, industry and competitive environment, intellectual property rights and potential for costs, disruptions and consequences of litigation, financing requirements and ability to access capital and other matters that are described in Affymax's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Affymax undertakes no obligation to update any forward-looking statement in this press release.
About Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology, gastroenterology and cardiovascular disease treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visit www.tpna.com.
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[i] National Kidney and Urologic Diseases Information Clearinghouse. “Anemia in Kidney Disease and Dialysis
[ii] Astor et al Association of Kidney Function with Anemia: The Third National Health and Nutrition Examination Survey (1988-1992). Archives of Internal Medicine 2002; 162: 1401-1408
[iii] National Heart Lung and Blood Institute “What is Anemia.” http://www.nhlbi.nih.gov/health/dci/Diseases/anemia/anemia_what is.html.
[iv] Centers for Medicare and Medicaid Services MEDCAC Meeting 3/24/2010 – Erythropoesis Stimulating Agents in Anemia Related to Kidney Disease. http://www.cms.gov/medicare-coverage-database/details/medcac-meeting-details.aspx?MEDCACId=52
[v] Fishbane et al. "Hemoglobin Cycling in Hemodialysis Patients Treated With Recombinant Human Erythropoietin." Kidney International 2005; Vol. 68 (2005), pp. 1337-1343
Takeda Global Research & Development Center, Inc., U.S.
Vice President, Corporate Communications