VIVUS, Inc. (Nasdaq: VVUS) today announced positive results from REVIVE (TA-301), a phase 3 pivotal study evaluating the safety and efficacy of avanafil, an investigational drug candidate for the treatment of erectile dysfunction (ED), in 646 patients. The REVIVE study met all primary endpoints across the three doses studied by demonstrating statistically significant improvement in erectile function as measured by the Sexual Encounter Profile (SEP) and improvements in the International Index of Erectile Function (IIEF) score. The pivotal study, conducted under a Special Protocol Assessment with the U.S. Food and Drug Administration (FDA), also demonstrated successful intercourse in 30 minutes or less, and a favorable side-effect and safety profile.
"Erectile dysfunction is a significant problem among more than half of all men over the age of 40. While sales of currently available ED therapies exceed $3.8 billion a year, persistent switching by patients suggests that patients are less than satisfied with current therapies," stated Leland Wilson, chief executive officer of VIVUS. "These phase 3 avanafil data not only confirm the robust efficacy we've seen in earlier trials, but potentially differentiate avanafil from other PDE5 inhibitors when it comes to side effects and time-to-onset of efficacy. We are confident that avanafil can effectively compete in the oral ED therapy market."
Highlights of the study include:
- Nearly 80% of sexual attempts among patients on the 200 mg dose of avanafil had erections sufficient for intercourse (SEP2)
- Full efficacy, as measured by successful intercourse, was reported by avanafil patients in 30 minutes or less
- Full efficacy was maintained for all doses across multiple time points from 30 minutes to beyond six hours
- All FDA-defined primary endpoints were met across all three doses of avanafil
- Avanafil was well tolerated as demonstrated by a high retention rate (85%)
- There were no drug-related serious adverse events in the study
- Avanafil patients had low reports of common PDE5i side effects
"Many patients living with chronic ED become frustrated by the occasional treatment-limiting side effects associated with currently available therapies. Patients often switch therapies in search for an improved experience," stated LeRoy Jones, MD, Clinical Associate Professor, Urology, University of Texas Health Science Center, San Antonio and an avanafil trial investigator. "The efficacy and safety data for avanafil underscore the potential role this next-generation PDE5 inhibitor may play in the lives of the millions of men living with ED, searching for new treatment options."
Dr. Jones added, "Another important consideration of patients is how quickly their ED therapy works; these data suggesting that avanafil achieves a full effect in 30 minutes or less, with a window of opportunity for intercourse extending beyond six hours, would be a welcome option for ED treatment."
The REVIVE study was a randomized, double-blind, placebo-controlled efficacy and safety study that evaluated three doses of avanafil in men with a history of general ED. The results of the phase 3 study showed:
- Patients achieved an overall improvement in erectile function, as measured by improvement in the International Index of Erectile Function (IIEF). IIEF scores range from 0-30 and measure the severity of erectile dysfunction as follows: severe dysfunction is less than or equal to 10; moderate is 11-16; and mild/minimal is 17-25. Results of the study were:
Baseline End of Treatment -------- ---------------- Placebo 12.4 15.3 Avanafil 50 mg 12.7 18.1 Avanafil 100 mg 12.6 20.9 Avanafil 200 mg 12.7 22.2>
Patients on avanafil had erections sufficient for penetration as measured by the Sexual Encounter Profile (SEP) question 2:
Baseline End of Treatment -------- ---------------- Placebo 47% 54% Avanafil 50 mg 45% 64% Avanafil 100 mg 46% 74% Avanafil 200 mg 48% 77% (p<0.001 vs. placebo) - Patients taking avanafil experienced successful intercourse as measured by the SEP question 3:
Baseline End of Treatment -------- ---------------- Placebo 13% 27% Avanafil 50 mg 13% 41% Avanafil 100 mg 14% 57% Avanafil 200 mg 12% 57% (p<0.001 vs. placebo) The most commonly reported side effects in patients taking avanafil (all doses combined) included headache (7.0% vs. 1.2% placebo), flushing (4.6% vs. 0% placebo) and nasal congestion (2.3% vs. 1.2%); there were no reports of visual disturbances such as "blue vision."
VIVUS had previously completed a phase 1 thorough QT prolongation (TQT) study evaluating 100 mg and 800 mg of avanafil. The study was successfully completed with no concern associated with QT prolongation.
"The high selectivity and rapid peak drug concentrations of avanafil make for a very attractive product profile, which is potentially associated with fewer side effects and faster onset of full efficacy - two attributes preferred by men looking for faster and more tolerable options. Full efficacy was seen in 30 minutes or less, and based on patient reported outcomes, the duration of full effect lasted beyond six hours. Based on these results, we believe that avanafil can be positioned as a true on-demand therapy for patients looking for a rapid response," said Wesley Day, PhD, vice president clinical development of VIVUS. "We're pleased with the promising results demonstrated with avanafil, and look forward to further advancing our clinical program toward filing an NDA for avanafil in late 2010 or early 2011."
Mr. Wilson added, "These compelling data for avanafil follow the recent positive phase 3 obesity data for QNEXA, for which we expect to file an NDA before the end of the year, placing VIVUS in the fortunate position of having two late-stage products addressing large markets with significant unmet needs and near-term regulatory and data milestones on the horizon. These assets, combined with our solid cash position, provide VIVUS with significant momentum as we end the year and look ahead towards 2010."
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