Washington Editor

The FDA Tuesday will ask an advisory committee to consider whether phosphate binders used to control serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis should be approved for use in predialysis patients for the treatment of hyperphosphatemia.

The phosphate binders currently approved for the U.S. market, Genzyme Corp.'s Renagel (sevelamer hydrochloride), Fresenius Medical Care's Phoslo (calcium acetate) and Shire Pharmaceuticals' Fosrenol (lanthanum carbonate), are indicated for patients on dialysis only.

In briefing documents issued Friday, the three firms argued that, given that CKD progresses as a continuum with subtle clinical distinctions between predialysis and dialysis, no distinction should be made regarding the treatment of hyperphosphatemia in patients based on their dialysis status.

The companies contended that there is "ample evidence to support earlier phosphate binder treatment" of patients with CKD and that "failure to do so is not in the best interest of patients."

The firms maintained that their position was consistent with that of the National Kidney Foundation's current guidelines and that no further studies were needed to support approval for the predialysis indication.

The FDA said that it does not question whether phosphate binders are effective in lowering serum phosphate in predialysis patients.

The question, the agency said, is whether there is adequate evidence of net clinical benefit to warrant recommending such use.

FDA is asking its Cardiovascular and Renal Drugs Advisory Committee to vote on whether serum phosphate is a validated surrogate for the clinical outcomes of patients with CKD on dialysis and predialysis patients and whether the approval for phosphate binders should be extended for use in predialysis patients.

In a research report, analyst Christopher Raymond of Baird & Co. Inc. said 5 percent to 10 percent of Renagel use is in the predialysis population. If phosphate binders are restricted to dialysis patients only, he said, it could lead to implications for Genzyme's Renagel.

"We do think this meeting poses a bit of a risk," he said.

If the FDA takes a hard-line stance on the predialysis indication for the three approved phosphate binders, Raymond said, it could push back the predialysis portion of the development program for Genzyme's Renvela, a next-generation buffered form of sevelamer. The firm filed a new drug application with the FDA for Renvela in December 2006.

If Genzyme is asked to conduct an outcomes study for Renvela, Raymond predicted, "this would delay the regulatory approval timeline."