By Debbie Strickland
GelTex Pharmaceuticals Inc. has initiated an 18-site, 560-patient Phase III trial of CholestaGel, a nonabsorbed cholesterol reducer for the treatment of hypercholesterolemia.
In this first of two Phase III studies, the company will evaluate efficacy and tolerability at four dosage levels over six months of treatment, with reduction of low-density lipoprotein (LDL) cholesterol serving as the primary endpoint.
A second Phase III trial, slated to begin in the second quarter of 1998, is a six-week study in 120 patients at six sites. The trial will evaluate once-daily and split-dosing regimens.
"We expect both Phase III studies to be completed by the end of 1998," said Mark Skaletsky, president and CEO of the Waltham, Mass., firm. If all goes well, "we're planning to file [a new drug application] in mid-1999."
CholestaGel is an orally delivered, non-absorbed hydrogel that binds and removes bile acids from the intestinal tract. This activity stimulates the liver to remove cholesterol from the bloodstream to reduce bile acids.
At the Phase II level, the drug significantly reduced LDL cholesterol levels in patients with elevated LDL cholesterol, achieving reductions of 20 percent with a four-grams-per-day dose.
Though the company will first pursue FDA approval of CholestaGel as a monotherapy, a fixed combination use may lie ahead, Skaletsky said.
In a Phase II trial of CholestaGel in combination with the anticholesterol agent, lovastatin, a low dose of CholestaGel administered with half of the lowest recommended dose of lovastatin reduced LDL cholesterol by 32 to 34 percent — a significant effect.
An estimated 24 million U.S. residents require drug therapy for elevated cholesterol levels, but only 6 million are receiving treatment, the company estimated.
GelTex filed its first new drug application with the FDA in November, for RenaGel, a nonabsorbed phosphate binder for the control of elevated phosphate levels associated with chronic kidney failure. That product is under development through a 50-50 joint venture with Genzyme Corp., of Cambridge, Mass. *