| By Emily P. Walker, Washington Correspondent, MedPage Today Published: December 07, 2011 |
 |
SILVER SPRING, Md. -- An FDA
advisory panel has voted 15-1, with one panelist abstaining, that the
synthetic erythropoiesis-stimulating agent (ESA) peginesatide should be
approved as an anemia treatment option for chronic kidney disease (CKD)
patients who are on dialysis.
The Oncologic Drugs Advisory Committee concluded that peginesatide, made by Affymax, appears to work as well as currently-available ESAs to raise hemoglobin levels and reduce the need for red blood cell transfusions in patients on dialysis. Unlike the other ESAs, which must be injected or administered intravenously as many as 13 times per month, peginesatide works with just one dose a month.
"There seems to be an advantage in terms of monthly dosing, [peginesatide] appears to be equally effective and doesn't have any safety signals," said panel chair Wyndham Wilson, MD, PhD, chief of the lymphoma division at the National Cancer Institute.
The FDA is not required to follow the advice of its advisory panels, but it often does. If approved, peginesatide would not be indicated for patients not on dialysis or patients with cancer. CKD patients, both on and off dialysis, currently use the ESAs epoetin alfa (Epogen and Procrit) and darbepoetin alfa (Aranesp). Those drugs are also indicated to treat anemia due to myelosuppressive chemotherapy.
The Oncologic Drugs Advisory Committee, which also deals with hematology issues, reviewed the company's four phase III randomized, controlled, open-label clinical trials, two of which involved CKD patients on dialysis and two of which involved CKD patients not on dialysis. The results of those trials were first presented at the American Society of Nephrology meeting in November 2010.
The primary efficacy endpoint for all the trials was the mean change in hemoglobin between baseline and the evaluation period (from 25 to 36 weeks, depending on the study).
Two safety endpoints were studied: a composite safety endpoint -- including the first occurrence of death, stroke, myocardial infarction, congestive heart failure, unstable angina, or arrhythmia -- and a composite of major adverse cardiac events, including first occurrence of death, stroke, or myocardial infarction.
In the trials involving patients on dialysis, safety outcomes were similar in both treatment groups, but in trials involving nondialysis patients, peginesatide performed worse than the comparator drugs. In the two studies combined, which involved a total of 983 patients (656 on peginesatide and 327 on darbepoetin), 22% of those on peginesatide experienced a safety event, compared with 17% of those on darbepoetin, a statistically significant difference.
Those findings led to the company requesting the drug be approved only for patients on dialysis. Panelists were not sure why the drug would work in patients on dialysis, but not in patients who are not on dialysis.
"We need to learn more and understand why there are differences between dialysis and nondialysis [patients]," said panelist Kevin Kelly, DO, professor of medical oncology at Thomas Jefferson University in Philadelphia.
One of two cardiologists on the panel, Steven Nissen, MD, of the Cleveland Clinic, was the only panelist who voted that the drug should not be approved. He took issue with the fact that none of the studies were blinded. Affymax said because the dosing for the two drugs was so different -- one required injections practically every other day and the other required once-monthly injections -- blinding would have been difficult.
The other cardiologist, Udho Thadani, MD, of the Oklahoma City Veterans Affairs Medical Center, abstained.
Jay Wish, MD, a nephrologist at Case Western Reserve University in Cleveland, Ohio, and consultant for Affymax, said approval of peginesatide likely wouldn't have a large impact on clinical practice. CKD patients who are on dialysis must undergo treatment 13 times a month, during which they also receive an ESA, usually epoetin alfa. If peginesatide were approved, CKD patients with dialysis could use it once monthly, but they would still have to receive dialysis 13 times a month, so it wouldn't add to convenience.
CKD patients who are are on home dialysis -- only about 10% of the dialysis population, according to Wish -- generally use darbepoetin alfa because of cost issues. Those patients must still go into a clinic to receive multiple ESA injections each month. Those patients could benefit from only having to get an ESA injection once a month, because it would mean just one visit to a dialysis center each month, Wish told reporters after the meeting.
The Oncologic Drugs Advisory Committee concluded that peginesatide, made by Affymax, appears to work as well as currently-available ESAs to raise hemoglobin levels and reduce the need for red blood cell transfusions in patients on dialysis. Unlike the other ESAs, which must be injected or administered intravenously as many as 13 times per month, peginesatide works with just one dose a month.
"There seems to be an advantage in terms of monthly dosing, [peginesatide] appears to be equally effective and doesn't have any safety signals," said panel chair Wyndham Wilson, MD, PhD, chief of the lymphoma division at the National Cancer Institute.
The FDA is not required to follow the advice of its advisory panels, but it often does. If approved, peginesatide would not be indicated for patients not on dialysis or patients with cancer. CKD patients, both on and off dialysis, currently use the ESAs epoetin alfa (Epogen and Procrit) and darbepoetin alfa (Aranesp). Those drugs are also indicated to treat anemia due to myelosuppressive chemotherapy.
The Oncologic Drugs Advisory Committee, which also deals with hematology issues, reviewed the company's four phase III randomized, controlled, open-label clinical trials, two of which involved CKD patients on dialysis and two of which involved CKD patients not on dialysis. The results of those trials were first presented at the American Society of Nephrology meeting in November 2010.
The primary efficacy endpoint for all the trials was the mean change in hemoglobin between baseline and the evaluation period (from 25 to 36 weeks, depending on the study).
Two safety endpoints were studied: a composite safety endpoint -- including the first occurrence of death, stroke, myocardial infarction, congestive heart failure, unstable angina, or arrhythmia -- and a composite of major adverse cardiac events, including first occurrence of death, stroke, or myocardial infarction.
In the trials involving patients on dialysis, safety outcomes were similar in both treatment groups, but in trials involving nondialysis patients, peginesatide performed worse than the comparator drugs. In the two studies combined, which involved a total of 983 patients (656 on peginesatide and 327 on darbepoetin), 22% of those on peginesatide experienced a safety event, compared with 17% of those on darbepoetin, a statistically significant difference.
Those findings led to the company requesting the drug be approved only for patients on dialysis. Panelists were not sure why the drug would work in patients on dialysis, but not in patients who are not on dialysis.
"We need to learn more and understand why there are differences between dialysis and nondialysis [patients]," said panelist Kevin Kelly, DO, professor of medical oncology at Thomas Jefferson University in Philadelphia.
One of two cardiologists on the panel, Steven Nissen, MD, of the Cleveland Clinic, was the only panelist who voted that the drug should not be approved. He took issue with the fact that none of the studies were blinded. Affymax said because the dosing for the two drugs was so different -- one required injections practically every other day and the other required once-monthly injections -- blinding would have been difficult.
The other cardiologist, Udho Thadani, MD, of the Oklahoma City Veterans Affairs Medical Center, abstained.
Jay Wish, MD, a nephrologist at Case Western Reserve University in Cleveland, Ohio, and consultant for Affymax, said approval of peginesatide likely wouldn't have a large impact on clinical practice. CKD patients who are on dialysis must undergo treatment 13 times a month, during which they also receive an ESA, usually epoetin alfa. If peginesatide were approved, CKD patients with dialysis could use it once monthly, but they would still have to receive dialysis 13 times a month, so it wouldn't add to convenience.
CKD patients who are are on home dialysis -- only about 10% of the dialysis population, according to Wish -- generally use darbepoetin alfa because of cost issues. Those patients must still go into a clinic to receive multiple ESA injections each month. Those patients could benefit from only having to get an ESA injection once a month, because it would mean just one visit to a dialysis center each month, Wish told reporters after the meeting.
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