A Goldilocks solution
If FDA heeds recommendations of an advisory panel, approved target hemoglobin levels for erythropoeisis-stimulating agents for chronic renal failure patients will end up being fairly close to where they were in March, when the agency changed them in reaction to evidence that higher targets were associated with an increased risk of death.
Although the wording may be different, the Hb targets will probably be functionally equivalent to the label Amgen Inc. has requested.
Although the round trip may seem pointless, last week's joint meeting of the Cardiovascular and Renal Drugs and the Drug Safety and Risk Management advisory committees demonstrated the complexity of the clinical reality and the paucity of hard data to guide use of ESAs in patients with kidney disease.
There have been about 8 million patient years of exposure to ESAs since Epogen, the first drug in the class, was approved 18 years ago, yet little research has been conducted to help physicians optimize their efficacy while avoiding unnecessary harm.
The few available postmarket studies of ESA outcomes involve targets below and above the range the drug sponsors recommend and that are suggested in clinical guidelines. These studies, along with observational data, paint a complex, nuanced picture.
Indeed, the panel members spent much of the meeting focused on an apparent paradox: attempting to increase Hb in kidney disease patients to levels approximating those in healthy individuals is harmful, but actually achieving higher Hb levels is usually beneficial.
The committee also grappled with the potential association between increased mortality risk and low response rates to ESAs, a circumstance that could affect as many as 40% of dialysis patients.
It also examined the potential adverse effects of gyrations in Hb levels brought about by trying to fine-tune levels around specific targets.
Along the way, the meeting chair and several members criticized the sponsors of ESAs for failing to generate the data needed to make good dosing recommendations.
In the end, the advisors concluded FDA should change the ESA labels to provide both clear goals for their use in treating anemia associated with chronic renal failure, as well as guidance on how to achieve those goals.
Thus, while it called for increased specificity, the panel also urged FDA to avoid establishing rigid specifications that would diminish physician discretion or tempt payers to create incentives to practice paint-by-numbers medicine that can put patient health at risk.
Roberta Wager, president of the American Association of Kidney Patients, captured the public health objective. "What we need is an FDA and Medicare policy that strives for a 'Goldilocks' solution on ESAs: not too much,