Proving there's more than one way to skin an overweight cat, Regeneron Pharmaceuticals Inc. reported favorable results from a Phase II dose-ranging trial to study the safety and efficacy of Axokine, its anti-obesity drug that ran into side-effects trouble about 15 months ago, prompting Procter & Gamble Co. to give up rights to the product.
In the Phase II study, Axokine, a genetically re-engineered version of ciliary neurotrophic factor (CNTF), helped patients lose an average of 10 pounds more than those given placebo, and they kept losing weight over the 12-week trial period.
Forty-six percent of the patients lost at least 10 pounds, compared with only 5 percent of those on placebo, and the drug was well tolerated, with no serious adverse events. What's more, in one treatment arm of the study, a group that got eight weeks of Axokine gained back no weight during four weeks of placebo afterward.
"It's a short time, but a good indicator," said Murray Goldberg, vice president of finance and administration and chief financial officer for Tarrytown, N.Y.-based Regeneron, adding that the lack of rebound weight gain is "consistent with what we've seen in animal studies as well."
The follow-up period will be extended to test the staying power of Axokine in a pivotal Phase III trial slated to begin in mid-2001, Goldberg told BioWorld Today.
So far, Axokine looks better than all other obesity drugs studied, including the two main marketed products, Meridia (sibutramine hydrochloride monohydrate) and Xenical (orlistat), said analyst Michael King, of Robertson Stephens in New York, who called Regeneron's a potential blockbuster drug in a research note issued Tuesday.
Xenical, a drug that generates $600 million per year in sales for Hoffmann-La Roche Inc., of Nutley, N.J., has been shown to induce less than a 6 percent weight loss at one year. Meridia, marketed by Knoll Pharmaceutical Co., of Mt. Olive, N.J., induced an 8 percent weight loss at one year.
Leonard Schleifer, president and CEO of Regeneron, told BioWorld Today the promise of the natural hormone leptin for obesity, which had been fading, may be pushed further into the background by Axokine.
"Leptin was the panacea," he said, although it has proved challenging in animal studies of diet-induced obesity. Axokine has a mechanism of action similar to leptin, binding to receptors and activating key signaling pathways to suppress appetite and reduce body weight.
The Axokine Phase II study, randomized, double-blind, placebo-controlled at seven U.S. sites, enrolled severely obese or morbidly obese patients, averaging 240 pounds. For two weeks, all got placebo. Then, 170 were randomized into five groups for the 12 weeks of treatment.
Significantly, researchers found no increase in herpes simplex virus (HSV) infections, or cold sores, in Axokine patients compared to those given placebo. In the fall of last year, P&G returned Axokine rights to Regeneron after preliminary data showed that, although patients on the drug lost weight and reduced their food intake, those in the higher dosage group experienced nausea, vomiting, and, in some cases, activation of their HSV, Goldberg said. (See BioWorld Today, Sept. 3, 1999.)
"We saw it in the high-dose part of the single-dose phase" of the Phase I study, he said.
Regeneron kept other aspects of the 1997 deal with Cincinnati-based P&G, and went ahead with Axokine on its own. Then, in August of this year, P&G pledged its continued faith in Regeneron by restructuring the firms' earlier deal in an arrangement that guarantees $64 million for Regeneron through 2005. (See BioWorld Today, Aug. 7, 2000.)
Research for P&G will be focused on muscle atrophy and muscular disease, fibrotic diseases and certain G protein-coupled receptors. Regeneron is developing injectable Axokine without a partner, and has a deal with Emisphere Technologies Inc., also of Tarrytown, to develop an oral version. (See BioWorld Today, March 10, 2000.)
Other programs Regeneron is independently pursuing are VEGF Trap, an antagonist to vascular endothelial growth factor, and brain-derived neurotrophic factor.
The company's stock (NASDAQ: REGN) closed Tuesday at $27.187, up $1.062.