New Labeling Restrictions for ESAs: ODAC

New Labeling Restrictions for ESAs: ODAC

SILVER SPRING, Maryland—The Food and Drug Administration (FDA) should require additional restrictions in product labeling and/or additional clinical trials before approving new erythropoiesis-stimulating agents (ESAs) or new indications for ESAs already on the market, the Oncologic Drugs Advisory Committee (ODAC) told the agency.

The ODAC panel made other major recommendations that, if accepted, would more tightly restrict the use of ESAs (see box on page 7). Its votes on issues with significant implications for patients and ESA makers followed a day-long meeting on the safety and efficacy of the drugs.

In 2004, ODAC reviewed ESA-related safety issues raised by two studies, known as BEST and ENHANCE. Since then, several additional studies have led to greater concern about the off-label use of ESAs, such as for anemia unrelated to cancer treatments; the hemoglobin level at which physicians may try to maintain their patients; and the drug's safety. Two ESAs are currently FDA approved, Aranesp (darbepoetin alfa, Amgen) and Epogen and Procrit (epoetin alfa, Amgen and Ortho Biotech, respectively).

Among the newer studies that have generated concerns about ESAs are:

• The 103 study, which evaluated 989 patients with active malignant disease who were not getting chemotherapy or radiation treatments in a phase III, randomized, placebo-controlled study. Researchers observed no significant reduction in red blood cell transfusions but did find more deaths in patients randomized to darbepoetin than to placebo after 16 weeks of treatment, 26% vs 20%. At 4.3 months median follow-up, the absolute number of deaths was greater in the darbepoetin arm. [See ONI May 2007, page 2.]

• DAHANCA 10, which evaluated 522 patients with head and neck cancer undergoing radiation and randomized to either darbepoetin or placebo. An interim analysis of 484 patients showed the darbepoetin arm had a 10% increase in local-regional failure (P = .01), and at study termination, the ESA group had a trend toward poorer survival (P = .08).


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