By Debbie Strickland

GelTex Pharmaceuticals Inc. completed its Phase II trial program for CholestaGel on an upbeat note, with a preliminary analysis of a low-dose combination study with lovastatin showing a significant reduction in cholesterol levels vs. placebo.

"The two drugs had at least additive efficacy when administered together," noted Steven Burke, vice president for clinical research. "It's also important to note that the drugs could be taken at the same time."

To date, GelTex, of Waltham, Mass., has tested CholestaGel in almost 500 patients, demonstrating "potent cholesterol-lowering activity in multiple settings, excellent tolerability and flexibility in dosing," said Mark Skaletsky, president and CEO, in a prepared statement.

Phase III trials of the product are slated to begin by the end of the year. Two studies are planned for the final phase of testing. Results are expected by the end of 1998, with a new drug application submission around 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.

Results of this latest Phase II trial, said the company, extend the potential applications of CholestaGel, previously tested alone, to combination therapy with the most widely prescribed class of systemic cholesterol-lowering drugs, HMG co-A reductase inhibitors, also called statins, which account for about half the cholesterol-reduction pharmaceutical market.

In the wake of the news, the company's shares (NASDAQ:GELX) jumped 17 percent to $26 Thursday, a $3.75 gain.

The company estimates the worldwide market for cholesterol reducers at more than $6 billion. Other members of the bile acid sequestrant family of drugs to which CholestaGel belongs have garnered a more than $140 million annual market in the U.S. alone. GelTex's product is designed for improved potency, lower dosages and fewer side effects, and could thus grow the market, according to the company.

The combination with lovastatin offers the prospect of an expanded market for CholestaGel, said Timothy Noyes, director of marketing, but is not the main thrust of the product's development.

The CholestaGel-lovastatin combination may be especially attractive to younger patients with high cholesterol levels, said Felicia Reed, an analyst with Cowen & Co., in Boston. Because of the lower dosage of lovastatin, the combination could be cheaper and less likely to produce the rare but worrisome side effects associated with statins.

With the string of positive trial data, including data showing the drug cuts cholesterol 20 percent as a monotherapy, Reed expects GelTex to attract a big pharma partner for CholestaGel, which the company has thus far developed independently.

"We've gotten the sense that there is a lot of interest in this product, and they're waiting for the right type of deal to come along," she said. "Financially, they're in good shape."

As of June 30, GelTex had $62.66 million in cash, cash equivalents and marketable securities, with net losses for the first half of the year totaling $13.34 million.

At Lower Drug Doses, Cholesterol Still Reduced

A preliminary analysis of the 130-patient Phase II study shows a low dose of CholestaGel administered with half of the lowest recommended dose of lovastatin slashed low-density lipoprotein (LDL) cholesterol by 32 to 34 percent.

The study was a randomized, double-blind placebo- controlled trial to evaluate the lipid-lowering effects of the two drugs used in combination at low doses (2.4 g per day of CholestaGel and 10 mg a day of lovastatin) compared with the same doses of each drug administered alone.

The recommended dosage for lovastatin as a monotherapy is 20 to 80 mg a day, which cuts LDL cholesterol by 19 percent to 39 percent, respectively. In a Phase II monotherapy trial, 4 g a day of CholestaGel reduced LDL cholesterol by 20 percent. In the study 130 patients with elevated blood cholesterol levels followed a four-week low-fat, low-cholesterol diet and then were assigned to one of five treatment groups: CholestaGel alone; lovastatin alone; CholestaGel and lovastatin administered simultaneously; CholestaGel and lovastatin administered four hours later; or a placebo.

After four weeks of treatment, patients receiving the two-drug combination simultaneously had an average 33.7 percent reduction in LDL cholesterol from baseline levels. Patients taking the split combination regimen had an average 31.7 percent reduction.

In comparison, the lovastatin group had an average 21.2 percent reduction and the low-dose CholestaGel group had an average 8.1 decrease in LDL cholesterol. Among placebo patients, there was a 0.7 percent increase in LDL cholesterol. The difference between placebo and all of the treatment groups was statistically significant.

Further analysis will show whether the combination group's results were statistically significant compared to the arms receiving the individual drugs. *