Are there other ways to reach ideal hemoglobin without the 'wonder drug?'

If you think of the history of erythropoietin like a championship football game, its clear that, for the first three quarters, the drug was in total command. The quarterback, running backs, wide receivers, the kicker, and the defense were all working in unison, racking up points.

The last quarter, however, has been a real doosey.

On June 26, The U.S. Food and Drug Administration reached an agreement with Amgen Inc., manufacturer of erythropoiesis stimulating agents Epogen and Aranesp, to change the labeling of both drugs by lowering the upper hemoglobin range of 12 g/dL for individuals with chronic kidney disease. The FDA said the new dosing recommendations are based on clinical trials showing that using ESAs to target a hemoglobin level of greater than 11 g/dL in patients with CKD provides no additional benefit than lower target levels, and increases the risk of experiencing serious adverse cardiovascular events, such as heart attack or stroke.

Last Friday, about a week after the FDA decision, the Centers for Medicare & Medicaid Services, which covers the drug for Medicare patients, modified the proposed language in its Quality Incentive Program to take out the floor on hemoglobins for end-stage renal disease patients. Previously, CMS had payment penalties in place if clinics dosed ESAs that sent hemoglobins over 12 and below 10 g/dL.

Clearly, CMS was waiting for the FDA ruling before releasing the proposed regs. The change to the hemoglobin quality measure would become effective for FY 2013.

The FDA has been wringing its hands over the hemoglobin range for some time. Sources told NN&I at the National Kidney Foundation in April that the agency was working with Amgen over the idea of eliminating the hemoglobin range. The deepest concern was in the upper level; recent trials, including CHOIR, CREATE, and more recently, TREAT, were showing that ESA-driven hemoglobins above 12 were leading to cardiac complications and death.

The problem with the FDA action and CMS's response is that while their efforts help relieve the pressure at the top and back away from the dangers of too much EPO, they are ambiguous about setting a floor for hemoglobins. One of the reasons Epogen was approved by the FDA in 1989 was to help kidney disease patients end their long struggles with anemia. Transfusions were effective, but short-lived; Amgen's Epogen offered a consistent hemoglobin range for thousands of patients who literally crawled home from their dialysis treatment three times a week. Without a recommended low range, will we return to those days?

For its part, the FDA defines the floor for CKD patients like this: "Therapy should be individualized to the patient and the lowest possible ESA dose given to reduce the need for transfusions." CMS's change to the QIP doesn't even mention that, simply indicating that clinics will be penalized if the hemoglobins are too high.

That leave it up to physicians to get the prescribing right and limit sending the hemoglobin level down so low to induce transfusions. With almost 25 years of a hemoglobin range far away from transfusions, finding a rate that is just on the cusp will be tricky.

With the new Medicare bundled payment system that took effect in January, dialysis providers have been looking for ways to cut back on EPO use because of its high cost. Preliminary data already shows that, in preparing for the impending bundle, dialysis clinics sampled by Dialysis Outcomes Practice Pattern Study researchers have already begun reducing EPO use and placing more patients on IV iron.

That's not a bad thing; it's important to remember that the FDA and CMS rulings are aimed at ESAs and their use in raising hemoglobins. Lesser use of the drug, while still achieving a hemoglobin level that benefit patients, is the best combination.

Are there other ways to achieve higher hemoglobins with lower ESA use? Maybe with the money saved by using lower doses of ESAs, clinics can look at other therapy options, like setting up short daily and nocturnal dialysis programs. These therapies have been proven to reduce overall drug use (though not specifically ESAs), reduce the impact of kidney disease on the cardiac system, and improve quality of life. Effective treatment of kidney disease means making people feel they don't have a chronic illness. Let's look at all the possibilities.