FDA Advisors Go Easy on Aranesp (darbepoetin alfa)

The FDA Cardiovascular and Renal Advisory Committee went easy today on Aranesp (darbepoetin alfa), the embattled erythropoeisis-stimulating agent (ESA).  After considering the implications of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), the committee recommended that no additional restrictions or label changes be made for the drug. However, the vote hardly represents a ringing endorsement of the drug by the committee. Instead, most members felt that the current label already reflects the findings from TREAT and sufficiently restricts the drug’s use. (Following the publication of TREAT a year ago the drug’s label was changed to reflect the increased risk of stroke observed in the trial.)

The committee voted 15-1-1 against withdrawal of the indication for chronic kidney disease (CKD) patients not on dialysis. The members also voted against adoption of the control arm of TREAT (rescue darbepoetin alfa when hemoglobin dropped below 9 g/dl) as the indication for the drug. They further voted that the drug did not require further restrictions for use in dialysis patients or in patients with CDK with a history of stroke.

Sanjay Kaul told CardioBrief that “higher hemoglobin does not a healthier patient make.” Further:

While we have valid evidence that hemoglobin targets over 13 g/dL are hazardous, we have no idea about a safe ceiling. Future trials need to address the role of lower hemoglobin targets and lower ESA doses. In addition a placebo arm needs to be considered in special populations (early CKD) to assess the off-target effects of ESA.

Darren McGuire told CardioBrief that although the panel endorsed the label modifications that have already been made, the members felt that the the paucity of data was frustrating, and had little idea if or how to extend the “pre-dialysis” observations to the existing dialysis population. McGuire feels that it may be acceptable to give darbepoetin as long as patients are informed of the risk:

The observed 1% increase in stroke risk per year is on the order of what we used to see with thrombolytic therapy; in that situation, we routinely got written informed consent from the patients given this predictable stroke risk. So, regardless of any further product label modifications/restrictions, I strongly endorse a written informed consent process highlighting the stroke risk for all patients initiating darbepoitin therapy.

“The label should be adjusted, but I just don’t think we have enough information to recommend a fixed dose,” said panel member Judith Hochman, in an AP news report.

“I don’t think we have enough evidence to make any changes right now,” panel member Henry Black told Bloomberg News.


  1. […] no clinical benefit for the drug in patients with chronic kidney disease. Results of TREAT prompted a dramatic FDA advisory committee meeting in 2010 followed by a major label revision in […]

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