ATLANTA, May 23 (UPI) -- A few years from now, men with erectile dysfunction may be able to treat their condition with a pill with effects lasting at least two days or go to the doctor's office for as gene-based injection allowing healthy sexual function for six months.
Eight years after Pfizer's Viagra ushered in a new era in treating ED, the initial rush of excitement among patients is wearing thin, and men are demanding new therapies that solve the most vexing problems associated with ED treatments, like having to plan their sex lives around a pill regimen or using treatments that wear off too quickly.
"My patients have been asking for longer-acting drugs with fewer side effects, or that fix their condition more permanently so they don't have to be as dependent on expensive, time-limited medications," Ramez Andrawis, assistant professor at George Washington University (GWU), who runs the ED clinic of Medical Faculty Associates at GWU, told United Press International.
At this week's American Urological Association annual meeting in Atlanta, researchers gave conference attendees an early glimpse into developing therapies that could make up the next generation in treating ED.
"What starts out as exceptional and radical turns into mainstream treatments," noted James Barada, with the New York-based Albany Center for Sexual Health.
One such potential therapy -- now in phase 2 studies -- is SLx-2101, a drug belonging to the same drug class as Viagra, Eli Lilly's Cialis and GlaxoSmithKline/Bayer's Levitra, called phosphodiesterase-5 (PD-5) inhibitors.
Preliminary data from the study show the drug treats ED for at least 48 hours, said Irwin Goldstein, a urologist who works as a consultant for the drug's sponsor, Brighton-Mass.-based Surface Logix.
"What's so cool and exciting about this drug is that (inside the body) the pro-drug turns into another drug. It has the ability to act quickly and last long," he said.
"Viagra has the ability to act quickly, and Cialis lasts long; but the new drug does both," Goldstein said.
By comparison, Viagra is fast-acting, but its effects begin to diminish after about four hours, while Cialis's effects are maintained for approximately 17 hours.
Goldstein explained that the novel PD-5 inhibitor is ingested into the body as a "primary drug," but once inside the bloodstream, is transformed into a secondary "metabolic" drug. The two drugs have half-lives of about 10 and 14 hours, respectively, but it is their overlapping and combined effects that give the patient sexual potency for 48 hours and possibly beyond, he told United Press International.
"You're getting the equivalent of two drugs when you take one drug," Goldstein said. Early pharmacodynamic data on SLx-2101 show that, at the 48-hour time point, the drug still has 10 times the dose needed to block the enzyme linked to ED and allow sexual function, he noted.
While new ED therapies are pushing the time between pills to longer and longer intervals, many patients are still bothered by the need to have to structure sexual activity around a regimen of medication.
Taking on that problem is New York-based Ion Channel Innovations, which has completed a phase 1 study of a gene-based ED therapy dubbed hMaxi-K. The company is banking on the therapy being approved as a locally injected ED treatment administered roughly every six months, said ICI directing member Arnold Melman, who spoke at the ED treatments briefing.
One of the 11 patients enrolled in the hMaxi-K study "felt like a kid again," said Melman, who is also a professor with the New York-based Albert Einstein College of Medicine, which owns a 12-percent interest in the gene therapy.
"With PD-5 inhibitors, you have to plan to take the drug before you want to have sex," he said, "but with hMaxi-K, you don't have to plan to take it. I think this lets you be normal."
Melman added that the treatment appears to have a "synergistic effect" when taken with PD-5 inhibitors like Cialis, suggesting that the gene-based ED therapy, if approved, shouldn't be limited to use in patients who have failed PD-5 inhibitor therapy.
For example, men might get a biannual injection of hMaxi-K, then augment the gene therapy with a low-dose PD-5 inhibitor and potentially have fewer of the side effects associated with the PD-5s, including nasal congestion and gastrointestinal problems, he said.
Melman also told reporters that ICI's phase 1 study showed that the treatment -- which works via a process called ion channel gene transfer -- is safer than the more widely publicized gene-based methods that use viral vectors, or viruses stripped of their RNA and implanted with a therapeutic gene.
Viral vectors have the inherent risk that they could regain their ability to replicate once inside the cell. "Gene transfer has gotten bad publicity and deservedly so," Melman said. On the other hand, ion channel gene transfer -- which mimics the action of calcium channel blocker drugs taken to control blood pressure -- is different because it uses "naked DNA" that, unlike viral vectors "just sits in the (cell's) nucleus," he explained.
Melman added that hMaxi-K performs its calcium channel-blocking function "only on demand."
Although researchers conducting the phase 1 study of hMaxi-K saw some expected adverse events, "most importantly, there were no gene transfer-related adverse events" among the 11 study patients with a median age of 59 years, he noted.
ICI's trial proved that hMaxi-K can be directly instilled into a local target organ of a human to create a tissue-specific, physiological, long-lasting effect, Melman said.
"We showed the technology works," Melman told the briefing. "This justifies going on to a phase 2 trial."
He said ICI hopes to launch that study this year, conditioned on sufficient funding.
Also speaking at the conference, Ajay Nehra of the Mayo Clinic in Rochester, Minn., released the preliminary results of a phase 2 study of avanafil -- dubbed TA-1790 -- which he billed as an "on-demand medication for sexual dysfunction."
Nehra said the drug's chief advantage is its shorter half-life. "Some patients might not want drug effects for a long time," he said.
He said early data from the 101-patient study is designed to compare avanafil with sildenafil (Viagra) and placebo, and is aimed at assessing the safety of avanafil following treatment with nitrates, a heart medicine taken by many older men who also want therapy for ED.
Nehra said that the study researchers saw some drop in blood pressure among treated patients but that this hemodynamic action was strongest when avanafil was dosed before nitrate therapy, but was undetectable if the time between avanafil and nitrate administration was 12 hours.
"This (nitrate) contraindication will continue to exist, but with a shorter (half-life) window, on-demand ED medication might be able to be used with (nitrates)," Nehra said. "Stay tuned for more studies."
He also noted that the adverse-event rate for all three treatments used in the study was 5 percent.
