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Back To Vidyya Topical Cream For Erectile Dysfunction Successfully Completes Phase II Clinical Studies

Study Appears In February, 2001 Urology

  • "Topiglan®" encouraged erections judged intercourse-competent in almost 6X as many moderate-to-severely impotent men as placebo in office trial by world- leading expert in erectile dysfunction

  • Study confirmed safety potential for millions of men who can't or shouldn't take current oral "ED" drug

  • Only "minor to mild" local symptoms both for active and placebo, no significant changes in vital signs

The February issue of Urology, a respected peer-reviewed specialty journal, carries a paper detailing a successful Phase 2 study demonstrating the safety and efficacy of Topiglan®, MachroChem's topical drug for erectile dysfunction (ED). The company has filed the results of this study with the U.S. Food & Drug Administration, and is now in a phase 3 pivotal trial to support an application for marketing approval.

Instead of a tablet or capsule like all other erectile-dysfunction drugs now in phase 3, Topiglan is a gel. Men will apply Topiglan to the glans ("head") of their penises at least 15 minutes before attempting intercourse. Topiglan's active ingredient, alprostadil, affects only the penis. Alprostadil should pose no risk to men prescribed nitrates or other drugs for a heart condition. MacroChem hopes Topiglan will become first-line therapy for all ED patients, including those who can't take Viagra® or Viagra® class ("PDE-5 inhibitor") drugs.

Irwin Goldstein, MD, a recognized authority on male and female sexual dysfunction, performed the randomized, placebo-controlled study at Boston University School of Medicine, and co-authored the UROLOGY paper. The patient base for the study was a group of 60 men with well-documented moderate-to- severe erectile dysfunction - typical of the difficult patients referred to the University's clinic. Many of the patients in the Topiglan study had failed to respond to Viagra® and other treatments for impotence.

"To simplify recruitment, we accepted all patients referred to us into this trial, including many who could obtain erections only with direct injection of vasoactive drugs into their penises, and even some who failed to respond to that therapy," Dr. Goldstein said. "You don't include such individuals when you're trying to optimize a trial to show efficacy."

"We were looking for more than evidence of potential efficacy - we were looking for potential local and systemic side effects, too" Dr. Goldstein explained. "We got valuable information documenting absence of serious local and systemic effects from men who didn't respond to Topiglan, as well as from men who did."

"In this tough group of patients, 38.9% of those who received Topiglan obtained an erection deemed capable of initiating and completing vaginal intercourse, versus 6.8% receiving placebo gel," Dr. Goldstein reported.

"The statistical difference between response to Topiglan and placebo was highly significant: p< 0.005 - meaning that the likelihood of pure chance producing such results is just 5 in 1000. The low (6.8%) placebo response may demonstrate the severity of the erectile dysfunction."

"These results demonstrate that MacroChem had good reason to proceed to a Phase 3 home trial, because Topiglan clearly showed potential for both good efficacy and safety in our very difficult tertiary-referral patient base," Dr. Goldstein said.

Topiglan is a topical gel combining prostaglandin E1 (alprostadil) and MacroChem's patented through-the-skin absorption-enhancing excipient known as Sepa®. Prior to Topiglan, alprostadil could be used to treat erectile dysfunction only if delivered in a highly invasive manner - either by injection into the penis with a hypodermic needle (Caverject®), or insertion into the urethra as a small suppository, with a syringe-like device (Muse®). Sepa is added to encourage sufficient absorption of alprostadil through intact skin to induce erection.

Minor to mild, transient local symptoms, no significant changes in vital signs According to Dr. Goldstein, local side effects were transitory and described by both Topiglan and placebo recipients as mild burning, stinging, tingling, or warmth upon application.

Those effects were typically reported only in the first few minutes after application, and were self-limiting (no treatment needed).

"The observed side effects are not an issue for use of the drug and should not interfere with its acceptance," said Dr. Goldstein.

The Urology article describes challenging "office-trial" details. Each patient participating in the Boston University study applied a dose of Topiglan or placebo gel to the glans of his penis under the supervision of a male nurse. The dose was administered in a private room, with the patient sitting on a bench, naked from the waist down.

Then, every 15 minutes, the nurse returned, and the patient would stand against a wall-mounted protractor, to have his penis angle photographed. At each measurement, the patient was asked to self-evaluate his penile tumescence and rigidity and about any abnormal sensations he felt. Instead of a partner, participating patients had to stimulate themselves with erotic movies and a vibrator.

Goldstein cautions against over-reading Phase 2 trials of ED drugs Dr. Goldstein, who was also the lead author of the landmark New England Journal of Medicine article on the Viagra® trials and is an investigator of many prescription ED drugs being developed worldwide, cautions against attempting to compare the results of this Topiglan study with results of any other erectile dysfunction drug trial.

"I would advise both physicians and the public against reading too much - positive or negative - into the specific efficacy numbers of any Phase 2 study," Dr. Goldstein explained.

"We're a tertiary referral center with experience in treating patients with complex ED problems," he said.

"Certainly, the present results should never be compared to home trials, where there's privacy and a partner and multiple attempt possibilities," he said. "In fact, you should never compare the results of any ED-drug clinical trial to that of another ED drug, because the patient groups are never comparable."

Paul Schechter, MD, PhD, vice president of drug development and regulatory affairs at MacroChem, and a co-author of the UROLOGY article, echoed Dr. Goldstein's observations on the trial findings.

"The outstanding efficacy and safety results in this tough group of patients, combined with our extensive portfolio of safety studies in both men and women, enabled us to proceed to our current pivotal phase 3 study," Dr. Schechter said.

Topiglan is now in a 460-patient, 30-center home trial, in which men with documented erectile dysfunction are randomized to Topiglan or a placebo, and given sufficient samples for up to 20 vaginal intercourse attempts each month, for three months. Results of the trial are expected later this year.

According to Dr. Schechter, the tolerance exhibited in the published study was not unexpected, because the active ingredient in Topiglan has such a long track record of safety in invasive ED therapies.

"Millions of men with ED worldwide have taken alprostadil safely for years in the form of an injection or an intraurethral suppository," Dr. Schechter said.

"Systemic effects of alprostadil are unlikely because the body metabolizes more than 80% of any alprostadil that enters the bloodstream in a single pass through the circulatory system," Dr. Schechter explains.. "The purpose of our phase 2 studies was to demonstrate the potential for clinically meaningful efficacy - which this study has shown among moderate-to-severe ED sufferers."

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