- "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.
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
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
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
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.
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
"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."