The Next Viagra?

July 10, 2000 -- In the two years since it rocketed onto the market -- and became, almost overnight, a household word -- the impotence drug Viagra has helped men with erection problems enjoy satisfying sex. The little blue pill fired the male imagination with the notion of an enduring and youthful virility that could last into the golden years.

However, the truth is that Viagra is not the absolute solution to the sexual concerns many men experiencing erectile dysfunction hoped it to be. Research indicates that as many as two in five men who try the drug don't experience the anticipated effects. Moreover, troubling statistics reveal that at least 39 Viagra users have died, primarily men taking other medications or those already suffering from severe heart disease (see the November-December 1998 issue of Clinical Therapeutics).

Given this backdrop, early reports of another potential contender emerged, tantalizing both the media and men left unsatisfied by Viagra’s effects. The very name of this new drug, Uprima, evoked images of supremacy and conquest, stirring hopes that a solution to impotence could be just around the corner.

When John Doe (a pseudonym) noticed his sexual function declining, he promptly sought guidance from his physician. Acquainted with Viagra (the brand name for sildenafil), Doe anticipated a straightforward solution. His doctor shared this sentiment and provided him with a sample of the medication to try at home. However, when the 59-year-old engineer from Cincinnati took the pill, he faced an unexpected disappointment.

It simply did not work.

Invasive treatments such as surgery, penile injections, or suppositories were not options for him, leaving Doe and his wife of 37 years to confront the unsettling reality that they might never again enjoy intimacy as they once did. “I started telling myself that gardening was more enjoyable than sex, just to cope,” he recalls.

However, Doe’s situation changed when his doctor invited him to participate in a trial of Uprima. The active ingredient in Uprima, apomorphine, has only a distant relation to morphine, and after eight months of using the experimental drug, he and his wife no longer worried about their sexual life. “I’ve been taking the drug two times a week, and it’s worked every time,” he states enthusiastically.

Doe was so impressed with Uprima that in April, he testified in favor of its approval before an FDA advisory committee; TAP covered his expenses for the trip to Washington.

Similarly, Robert Carelli, a 69-year-old retired teacher from Thousand Oaks, Calif., participated in a Uprima trial for nearly a year and initially experienced significant benefits from the drug.

Serious side effects occurred more frequently among men who received 4 milligrams or more of the drug, compared to those taking 2 milligrams. However, the efficacy of the lower dose was so limited that FDA medical reviewer Mark Hirsch, MD, asserted before an agency advisory committee in April, “Few patients will actually choose to remain on the 2-milligram dose when given the option of higher dosages.”

Despite the emerging concerns surrounding Uprima, the advisory committee voted 9 to 3 in favor of recommending FDA approval. With TAP's recent withdrawal of its application, the FDA will not make any decisions regarding the drug until the manufacturer resubmits its request, which the company has pledged to do upon completing two ongoing clinical trials.

“We remain very confident,” TAP spokesperson Kim Modroy told WebMD. “We hope that by taking this additional time, we can present a significantly improved product.”

If Uprima receives FDA approval, it will inevitably be compared to its well-known predecessor. While both Viagra and Uprima facilitate erections, they do so through different mechanisms. Viagra operates on the vascular system, temporarily dilating arteries to enhance blood flow to the penis. In contrast, Uprima targets the brain, inhibiting specific pathways that manage the body’s smooth muscle contractions. By restraining these contractions, Uprima allows for increased blood flow, theoretically leading to similar positive outcomes.

The routes through which these drugs affect the body also differ. Viagra is an oral medication taken in pill form, while Uprima is a lozenge designed to dissolve under the tongue. This unique delivery method enables Uprima to bypass the stomach and enter the bloodstream more rapidly than Viagra. This feature gives Uprima an edge regarding spontaneity, as it can be taken shortly after a meal. Conversely, Viagra loses its effectiveness if ingested on a full stomach, which can be a significant drawback when romantic dinners conclude with dessert.

Neither drug acts as an aphrodisiac: While they facilitate the process of achieving an erection, neither can enhance sexual desire nor increase libido. They cannot instigate feelings of attraction toward a partner that wouldn't naturally exist.

So, which medication appears to be superior? “There is no definitive answer yet,” remarks Ira Sharlip, MD, an assistant clinical professor of urology at the University of California at San Francisco, who has been involved in clinical trials for both medications. He emphasizes that further research is essential to draw any solid conclusions.

Clinical trials reveal that both Uprima and Viagra possess efficacy rates ranging from 50% to 60%, contingent upon dosage and the specific criteria for success (May 14, 1998, New England Journal of Medicine and discussions from the May 2000 American Urological Association meeting). However, a comprehensive head-to-head clinical trial comparing Viagra against Uprima has yet to occur.

Some patients may prefer Uprima due to its rapid onset of action, achieving peak effectiveness in about 15 minutes, compared to Viagra's hour or longer onset. Nonetheless, this rapid effectiveness comes with its drawbacks. Approximately 15% of men involved in the Uprima clinical trials reported nausea following use, with some experiencing more severe reactions.

Should Uprima receive FDA approval, many providers and patients might still opt for Viagra due to its familiarity, according to Robert P. Nelson, MD, a professor of urology at the Medical University of South Carolina in Charleston. Given that Pfizer, Viagra's manufacturer, has enjoyed a monopoly in the market, it has developed a robust marketing and sales force that could pose challenges for Uprima's entry into the arena.