In the latest of several moves to improve dosing options and expand patient populations for its drugs, Genzyme Corp. filed a new drug application with the FDA for Renvela (sevelamer carbonate), an improved formulation of Renagel (sevelamer hydrochloride) for the control of serum phosphorus levels in chronic kidney disease patients on dialysis.
Elevated serum phosphorus is common in dialysis patients and has been linked to increased risk of cardiovascular mortality, so phosphate binders often are prescribed to clear the excess phosphorus in food from the body. Renagel is the most-prescribed phosphate binder in the U.S., bringing in $134.7 million in revenues in the third quarter and a projected $495 million to $505 million overall for 2006. Yet the hydrochloride in Renagel also is difficult for the kidneys of dialysis patients to clear and can bind with carbonate and lower bicarbonate levels in the blood, resulting in acidosis.
John Butler, president of Genzyme Renal, said acidosis is "not a safety concern" for patients on dialysis, but switching out the hydrochloride for carbonate allows Genzyme to "offer a better product."
Both Renagel and Renvela offer potential benefits over calcium-based phosphate binders, the company said. Last month, Genzyme presented data at the American Society of Nephrology annual meeting from the largest prospective dialysis outcomes study ever conducted showing that patients using Renagel experienced lower rates of hospitalization, fewer days in the hospital, and reduced overall health care expenditures compared to patients treated with calcium-based phosphate binders. Renagel also offers a significant reduction in LDL cholesterol, and Butler referenced data correlating the higher rate of calcification in patients on calcium-based phosphate binders to a significantly higher mortality rate over five years.
Yet Renvela has additional benefits, both for patients and for Genzyme. While Renagel is approved only for patients on dialysis, Genzyme already is conducting a pivotal trial with Renvela in hyperphosphatemic patients with chronic kidney disease who have not progressed to dialysis. As soon as the Renvela NDA is approved, which Genzyme anticipates could occur in late 2007 based on a standard 10-month review cycle, the company will be ready and waiting to file for an expanded label in the pre-dialysis patient population. While there are about 350,000 dialysis patients treated by nephrologists in the U.S., the number of patients with chronic kidney disease managed by nephrologists is estimated at 1 million.
Additionally, while Renagel is dosed in tablets taken three-times daily (with every meal), the Renvela formulation allows Genzyme to explore once-daily dosing with a powdered version of the drug that could be dissolved in water. The company anticipates that the formulation would be particularly attractive to pre-dialysis chronic kidney disease patients and is conducting a pivotal trial that compares the powdered form of Renvela to Renagel. Both Renvela pivotal studies have completed enrollment.
"When we acquired the Renagel program from GelTex [Pharmaceuticals Inc.] back in 2000, we said it had $1 billion potential," Butler said. "Expanding the label is what's going to get us there."
The Renvela/Renagel product line is one of several in which Cambridge, Mass.-based Genzyme is seeking to expand market share. Last month, the company announced preliminary data indicating that a single-dose regimen of Synvisc (hylan G-F 20) resulted in a statistically significant improvement in pain from osteoarthritis of the knee compared to placebo. Synvisc is approved in a three-injection dosing regimen, but Genzyme plans to submit a request for a label amendment based on the data in the first half of 2007.
Clolar (clofarabine) is another example - the drug is approved for the treatment of children with refractory or relapsed acute lymphoblastic leukemia, but Genzyme is conducting Phase II trials in pediatric acute myelogenous leukemia and in adult patients with refractory or relapsed acute myelogenous leukemia. Other studies looking at combination treatments and other indications also are under way. Similarly, Campath (alemtuzumab for injection) is approved for B-cell chronic lymphocytic leukemia, but Genzyme sees potential for the drug and is conducting studies in non-Hodgkin's lymphoma and multiple sclerosis.
"When you have a gold standard on the market, you want to protect and expand that market," Butler said, adding that Genzyme's corporate strategy is to try to make its products available to everyone who would benefit from them.