By Lisa Seachrist
WASHINGTON — GelTex Pharmaceuticals Inc. submitted to the FDA a new drug application (NDA) Monday for its first product, RenaGel, a non-absorbed phosphate binder for the control of elevated phosphate levels associated with chronic kidney failure.
Should RenaGel win approval, the Waltham, Mass., company will commercialize the product with Genzyme Corp., of Cambridge, Mass., under a 50-50 development and commercialization partnership worth a potential $27.5 million to GelTex. The alliance was announced in June. (See BioWorld Today, June 19, 1997, p. 1.)
"It's a very important and very exciting time for GelTex," said Mark Skaletsky, president and CEO of GelTex. "From Phase I to filing our NDA was three years. That is pretty aggressive in terms of drug development."
Skaletsky credits the speed with which GelTex was able to file the RenaGel NDA to the fact that the product is not absorbed or processed by the body, which eliminated a number of safety concerns. And he noted the "efficacy data were quite clear."
Healthy kidneys maintain a delicate balance between phosphorus and calcium levels in the bloodstream by excreting excess phosphorus in the urine. Patients with chronic kidney failure are unable to use this mechanism to remove phosphorus. Instead, their bodies compensate by releasing excess parathyroid hormone and scavenging calcium from their bones in order to maintain the correct balance. As a result, many kidney dialysis patients suffer from a severely weakened skeletal system that is prone to fracture.
RenaGel is polymer hydrogel that binds phosphate from the diet — primarily from proteins — in the intestine and prevents it from ever reaching the bloodstream in the first place. Ultimately, RenaGel and the bound phosphate are excreted from the body.
"This is a nice, elegant way to deal with excess phosphorus for these patients," said Paul Mellett, chief financial officer for GelTex.
Currently, the only FDA-approved treatment to prevent excess phosphorus buildup in kidney failure patients is calcium acetate, although physicians use calcium carbonate as well. These calcium-based therapies are only effective at doses so high that patients may suffer from high blood calcium levels — hypercalcemia — which results in nausea and dizziness and can lead to life-threatening heart complications.
In addition to calcium-based therapies, physicians also use aluminum hydroxide off-label to bind excess phosphorus. However, aluminum is absorbed and can cause bone disease and dementia.
"We are hoping this product will take a lot of the worries off the shoulders of nephrologists as they try to treat these patients," Mellett said.
Two Phase III Trials Support RenaGel NDA
GelTex proved in a Phase III clinical trial involving 172 patients that RenaGel significantly lowered serum phosphorus concentrations without causing the hypercalcemia associated with calcium acetate.
A second Phase III trial in 82 patients showed that RenaGel worked just as well as calcium acetate, but didn't have the associated risk of hypercalcemia.
"Because the phosphorous comes in through the diet, these patients often need to severely reduce their protein intake and consequently can suffer from malnutrition," Skaletsky said. "This is really the No. 1 quality of life issue for patients on kidney dialysis."
Currently, 95 percent of all dialysis patients must take some form of phosphorus binder.
Under the 50-50 development and commercialization deal with Genzyme, the two companies formed RenaGel LLC. Following FDA approval, GelTex will provide to the partnership RenaGel, the product's patents and technology and the company's expertise in chronic renal failure. Genzyme will provide marketing and sales expertise and infrastructure as well as international regulatory support.
GelTex has an agreement with Chugai Pharmaceuticals, of Tokyo, to develop RenaGel in Japan and other Pacific Rim countries.
"We are really hoping that RenaGel will become the standard of care," Skaletsky said.
GelTex and Genzyme reported the NDA submission late Monday afternoon. GelTex (NASDAQ:GELX) closed at $29.125, down $0.375. Genzyme (NASDAQ:GENZ) ended the day at $27.50, up $0.125. *