By Lisa Seachrist

Washington Editor

Zonagen Inc.¿s stock plummeted 46 percent on news that the company and its development partner, Schering-Plough Corp., have decided to skip a scheduled June meeting of an FDA advisory panel reviewing their erectile-dysfunction drug, Vasomax.

The companies, instead, will receive a non-approvable letter for the product, and seek to amend their new drug application (NDA) once further studies being conducted by Madison, N.J.-based Schering-Plough have been completed.

The additional trials are expected to be completed sometime at the end of this year or in early 2000.

¿It was a tough decision for us,¿ said Joseph Podolski, president and CEO of The Woodlands, Texas-based Zonagen. ¿But I believe Schering-Plough knows how to market a drug. They see there is an opportunity to establish a detailed database that will give patients and physicians the information they need to decide if Vasomax is appropriate for them.¿

Zonagen¿s stock (NASDAQ:ZONA) closed Monday at $10.6875, down $9.125 a share.

The basis for the NDA the companies submitted in July 1998 was two positive pivotal Phase III studies of Vasomax, an immediate-release oral formulation of phentolamine mesylate, which works as a short-term alpha-adrenergic blocker. By blocking the alpha-adrenergic receptors, smooth muscle relaxes, creating vasodilation.

The pivotal studies were of a ¿four-attempt nature,¿ where the researchers scored the drug against a placebo in four attempts at sexual intercourse. The drug showed a statistically significant benefit in helping patients achieve successful vaginal intercourse as compared to placebo. After the four-attempt trials, patients were allowed to participate in an open label study of the drug.

Those studies have shown a continued and increasing benefit for patients taking Vasomax, but they are not randomized, double-blind clinical studies and are, therefore, not as persuasive. Podolski said Schering-Plough wanted to obtain more detailed long-term clinical data on both the safety and efficacy of the drug before bringing it in front of an advisory panel.

A key factor in the decision was the fact that Pfizer, of New York, already has approval to market Viagra (sildenafil citrate) for erectile dysfunction. Several recent reports have indicated that patients with cardiovascular disease taking nitrates may be at risk for fatal drug interactions should they take Viagra.

¿We have a growing list of drug interactions that we know of,¿ Podolski said. ¿But, we¿ve had no deaths from taking nitrates with this drug in the open label study. Schering-Plough is examining the use of nitrates in their studies.¿

Vasomax may have received a recommendation for approval from the advisory panel but, because Vasomax will be a consumer-driven pharmaceutical that is designed to treat a non-life-threatening condition, Schering-Plough wanted to have more clinical data to answer the questions the physicians and patients may have about the drug, Podolski said.

¿The market for this drug will be driven by consumer opinion,¿ Podolski said. ¿In the end, we want to flesh out the efficacy and safety data as much as we can.¿

By receiving the non-approvable letter, the companies will be able to supplement the NDA with the new clinical data. Once the supplement is submitted, the FDA will have six months to render a decision on Vasomax.

Schering-Plough is continuing to seek regulatory approvals for Vasomax in countries outside the U.S., having launched the product in Mexico and Brazil.

Erectile dysfunction is believed to afflict an estimated 48 million men between ages 40 and 70 in the U.S., Canada and Europe. Of those cases about 70 percent are believed to be caused by conditions ¿ such as diabetes, kidney disease, chronic alcoholism, multiple sclerosis, atherosclerosis and vascular disease ¿ that damage arteries, smooth muscles and fibrous tissues.

Zonagen, which focuses on the areas of urology, female health and contraception, has three female contraceptives in development, as well as a clinical program for Vasofem for the treatment of female sexual dysfunction. n