Washington Editor

Certain obese patients treated with Axokine, a drug candidate developed by Regeneron Pharmaceuticals Inc., have been shown to lose up to 7 percent of body weight after a year, the company said Monday.

In response, Regeneron's stock (NASDAQ:REGN) soared $2.93 Monday, or 41.5 percent, to close at $9.99.

Well, maybe Regeneron had a little help.

A number of companies working in the vascular endothelial growth factor (VEGF) arena got a shot in the arm Monday when South San Francisco-based Genentech Inc. released promising data from a Phase III trial of its VEGF candidate for metastatic colorectal cancer, Avastin.

Regeneron is developing an earlier-stage VEGF cancer product, currently referred to as VEGF Trap.

Nevertheless, Regeneron was riding high Monday, quite a distance from its price in early April when the company released preliminary results of the Phase III trial of Axokine, a genetically re-engineered version of ciliary neurotrophic factor, in overweight and obese patients.

The company's stock was down 56.6 percent to close at $7.52 on the preliminary analysis. The trial was designed to compare weight loss for people treated with Axokine plus a weight-control program that included diet and lifestyle modifications with weight loss for participants on a weight-control program who received placebo. (See BioWorld Today, April 7, 2003.)

Leonard Schleifer, Regeneron's CEO, told BioWorld Today at first glance the company noticed a larger number of Axokine patients lost at least 5 percent of their body weight compared with control patients (25.1 percent vs. 17.6 percent, p<.001 class="text">"The market perceived that as somewhat of a disappointment because they were hoping for a bigger efficacy," Schleifer said. "We looked at the data additionally and what we realized is that we had an overall effect. We confirmed that statistically, but we also think we've identified an approach that's allowed us to target the drug to people who are most likely to benefit."

Further analysis of the data demonstrated that any patient who did not respond to Axokine after three months likely would not respond after a year. "About one-third of the people actually do quite well," he said. "They lose about 17 pounds, or about 7 percent of their body weight, at the end of the year. So, that's a medically significant amount of weight. The patients can expect improvements in their co-morbidities such as hypertension and blood glucose."

The medically significant standard for weight loss is usually about 5 percent of body weight. "Data shows that if you can lose about 10 to 12 pounds on any mechanism, you decrease your risk of becoming a diabetic by 50 percent, so this data is very medically meaningful," Schleifer said, adding that those weight-loss rates should not be confused with cosmetic weight loss.

Results of the Phase III trial were released over the weekend at the American Society of Hypertension annual meeting in New York.

According to the company, patients who were early responders in the Axokine group averaged 14.4 pounds of weight loss at three months and 16.6 pounds at one year. Schleifer said 60 million Americans suffer from obesity.

The double-blind, randomized, placebo-controlled trial included 501 placebo-treated patients and 1,467 drug-treated patients at 65 U.S. centers. Average baseline weight for participants was about 235 pounds.

Schleifer expects to meet with the FDA soon to discuss additional trials.

Regeneron discovered and owns 100 percent of Axokine. The company is considering partnering alternatives. At one time, Axokine was partnered with Procter & Gamble, which dropped it in 1999 after preliminary Phase I results showed effective doses for treatment of obesity and diabetes may be safe only in herpes simplex virus-negative patients.

Axokine also is being studied in obese patients with diabetes. Statistically significant results from a Phase II study were released last month. (See BioWorld Today, April 15, 2003.)