By Mary Welch

GelTex Pharmaceuticals Inc. and partner Sankyo Parke-Davis are celebrating as the FDA approved their lipid-lowering agent, Welchol, for the reduction of elevated low-density lipoprotein(LDL) cholesterol in patients with primary hypercholesterolemia, or elevated blood cholesterol levels.

Welchol (colesevelam hydrochloride), formerly called Cholestagel, was approved as a monotherapy as well as in combination with an HMG-CoA reductase inhibitor (statin) as an adjunctive therapy to diet and exercise in these patients.

"We are very excited about this for a couple of reasons," said Mark Skaletsky, Waltham, Mass.-based GelTex's president and CEO. "The first is that this is the second product in 18 months that we've taken from discovery through approval ourselves. The first was Renagel."

Another reason is that Skaletsky said only a handful of biotechnology companies "have taken a product from discovery through approval themselves. There's not a lot of companies in that category. We've identified Amgen, Immunex, Chiron, MedImmune, and maybe BioChem Pharma. That's pretty great company."

Skaletsky also was pleased that Welchol was approved as a stand-alone therapy as well as in combination with statins.

"The approval was quicker than anticipated," said Peter Drake, vice president and senior biotech analyst with Prudential Vector Healthcare in New York. "The approval is a strong statement of testimony to the ability of this company's management to get drugs approved. It's quite an accomplishment. It speaks volumes for the management team and they deserve to be gratified by it. They're a very young company and they have two FDA-approved drugs."

Bill Tanner, vice president of SG Cowen Securities Corp. in New York, said the news was positive for GelTex. "Renagel may not be a blockbuster and Welchol may not be a blockbuster. But the company's management is certainly able to get a drug approved more than once. How they do remains to be seen, but lots of so-called blockbuster drugs never get to market. There are only a few biotech companies that have put two products on the market. How Welchol does will depend on how it differentiates itself from the other products and what type of sales job Sankyo does."

Welchol 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 Welchol. The drug is taken with a meal when the bile acids are most plentiful in the digestive tract.

The outcome is that LDL cholesterol is cleared from the blood, resulting in decreased serum LDL - or "bad" - cholesterol levels. Clinical studies demonstrated that Welchol reduced total cholesterol, along with LDL cholesterol, and increased high-density lipoprotein (HDL) - or "good" cholesterol.

"There are few, if any, toxicity issues because everything is excreted normally," Skaletsky said. "The LDL cholesterol is taken from the blood and it goes to the liver where it is excreted. Nothing is absorbed."

In the clinical trials, more than 1,400 patients received treatment lasting anywhere from four to 50 weeks. The side effects were similar to placebo, with the most common being flatulence and constipation. Welchol is contraindicated in individuals with bowel obstruction and in those who have shown hypersensitivity to any of the components of Welchol.

The company tested Welchol in conjunction with several cholesterol drugs known as statins, including New York-based Merck and Co. Inc.'s Mevacor (lovastatin) and Zocor (simvastatin), as well as Morris Plains, N.J.-based Warner-Lambert Co.'s Lipitor (atorvastatin). These drugs account for about 97 percent of all sales of cholesterol-reducing drugs in the U.S., GelTex said.

About 52 million people in the U.S. have at least mild hypercholesterolemia and would benefit from lipid-lowering therapy. Studies have shown that elevated levels of total and LDL cholesterol and decreased levels of HDL cholesterol are associated with development of atherosclerosis, the company said.

Niche Drug In A Large Market

Sankyo expects the drug to reach $300 million in three years, it said recently.

"I hope they're right," Drake said. "We've been putting it at $100 million in three years. It's not a blockbuster drug. It's being positioned as a niche in a huge market. All they need to do is pick up single-digit numbers of this segment and they've got a meaningful drug. For us, it's too early to call. That's why we're carrying our numbers on the conservative side. I do think it's too early for management to do a victory lap because we don't know whether it'll be a huge drug or not."

The approval prompted a $20 million milestone payment from Sankyo Parke-Davis, which is a joint venture of Tokyo-based Sankyo Pharma Inc., and Parke-Davis, a division of based Warner-Lambert. Sankyo Pharma late last year pledged up to $75 million for Welchol and a second-generation product, GT102-279, now in Phase II trials. To date, GelTex has received $30 million in milestones and is reimbursed for the development costs of GT102-279. GelTex funded Welchol's development. (See BioWorld Today, Nov. 16, 1999, p. 1.)

"We're going to spend a few bucks and throw a party," Skaletsky said about the $20 million milestone.

"The acceptance came a littler earlier than expected, so we changed our numbers to reflect the $20 million in the second quarter rather than the third," Tanner said.

Sankyo Pharma now will be responsible for the worldwide commercialization of Welchol, with GelTex receiving royalties on sales. Sankyo expects the product to be available by September. No price has been set yet, Skaletsky said.

Renagel (sevelamer hydrochloride), a non-absorbed polymer-based phosphate binder for patients with end-stage renal disease, was approved in November 1998. It is marketed through a joint venture with Cambridge, Mass.-based Genzyme Corp.

GelTex's stock (NASDAQ:GELX) closed Tuesday at $19.125, up $1.25.