By Lisa Seachrist
GelTex Pharmaceuticals Inc. submitted a new drug application to the FDA seeking approval to market its cholesterol-lowering polymer, Cholestagel (colesevelam hydrochloride).
This marks the second product the Waltham, Mass.-based company has submitted to the agency for review. In November 1998, the company and its marketing partner, Cambridge, Mass.-based Genzyme Corp., received approval for RenaGel (sevelamer hydrochloride), a non-absorbed polymer-based phosphate binder for patients with end-stage renal disease.
GelTex is requesting approval to market Cholestagel as a treatment for hypercholesterolemia, or elevated blood cholesterol levels, both as a monotherapy and in combination with the blockbuster class of cholesterol drugs known as statins.
"We are very happy to move forward with this submission," said Mark Skaletsky, president and CEO of GelTex. "[Rather than a priority review], we anticipate a normal review for Cholestagel."
Cholestagel is a non-absorbed hydrogel that binds and removes bile acids from the intestinal tract. Because bile acids are needed to digest food, the liver will recruit artery-clogging LDL cholesterol in the bloodstream and convert it into bile acids to replenish what's been bound by Cholestagel. The drug is taken with a meal when the bile acids are most plentiful in the digestive tract.
"It basically binds the bile acids so the liver pulls LDL cholesterol out of the bloodstream," Skaletsky said.
The company is relying on two Phase III studies and several Phase II studies to support the approval of Cholestagel. The first Phase III study evaluated 466 patients over six months and showed reductions of LDL cholesterol of between 15 percent and 20 percent. The second Phase III study evaluated a once-a-day dosing schedule vs. twice-a-day dosing. In that study, the company found the once-a-day dosing schedule was as effective as splitting the dosage between two meals, which added considerably to patient convenience.
"We wanted to get an indication for Cholestagel as a monotherapy, so our Phase III program looked at the cholesterol-lowering ability of Cholestagel alone," Skaletsky said.
The Phase II program was designed to show that Cholestagel offered an additive effect to the commonly prescribed statin therapy. The company tested the drug in conjunction with New York-based Merck and Co. Inc.'s Mevacor (lovastatin) and Zocor (simvastatin), as well with Morris Plains, N.J.-based Warner-Lambert Co.'s Lipitor (atorvastatin), and found the combination of a statin drug and Cholestagel to be superior to either drug alone.
"We discussed this strategy with the FDA," Skaletsky said. "We'd like to get the label to say that Cholestagel is effective in combination with statins and there is an additive effect."
In addition to Cholestagel, the company is testing second-generation versions of Cholestagel that GelTex said are twice as effective and may offer patients and physicians a means of lowering the dosage of statin medications.
The company reported sales for the newly approved RenaGel to have hit $8 million in the first six months of marketing.
GelTex's stock (NASDAQ:GELX) closed at $14.062 Friday, up 50 cents per share.