Futura Medical has announced Phase 3 data on its topical erectile dysfunction treatment MED3000, clearing the path for an FDA filing that could make the therapy an over-the-counter treatment option for erectile dysfunction.
Phosphodiesterase type 5 inhibitors (PDE5is) such as Viagra (sildenafil) and Cialis (tadalafil) and generic equivalents currently dominate the erectile dysfunction market.
Sildenafil and tadalafil are among the most widely prescribed drugs on the market.
“Whilst PDE5is are effective treatments, they have certain drawbacks,” said Ken James, executive director and head of R&D of Surrey, UK–based Futura Medical.
For one thing, PDE5i side effects can include headache, flushing, nasal congestion and back pain. In addition, FDA has repeatedly warned about the potential of synergistic hypotensive effects resulting from combining PDE5is with nitrates.
Ken James
In addition, PDE5i are “on demand” products, James said. That is, they generally take 30–60 minutes to act. “The need for pre-planning for sex results in around 25% of uses not leading to intercourse exposing patients to unnecessary drug use and possibly long-lasting side-effects,” James said. “Up to 50% of PDE5i users stop treatment within one year.”
Futura’s topical MED3000 could alter the ED treatment landscape significantly. “The topical gel formula, applied to the glans penis, has been proven to be effective in two Phase 3 studies of 12- and 24-week duration, in mild, moderate and severe ED,” James said.
Futura notes that the fast-acting nature of MED3000 can help men get an erection within 10 minutes. “Therefore, sex can be spontaneous, and the product can be used as part of foreplay,” James said.
A topical gel, MED3000, is technically a medical device rather than a drug. “It has an excellent safety profile,” James said.
Its safety profile was superior to that of tadalafil in a recent Phase 3 study. In addition, a single instance of localized mild penile burning was recorded in 1551 intercourse attempts. “No local side effects were recorded in female partners,” James added.
In the FM71 study, MED3000 had a superior safety profile over 5 mg of tadalafil. In that study, 19% of tadalafil recipients had a headache, while 4% of MED3000 users did. Similarly, 4% of the tadalafil arm reported either backache or chest pain, while 0% of MED3000 users did. MED3000 users, however, were more likely to experience nausea. A total of 4% of the MED3000 group reported that symptom compared to no tadalafil recipients.
“Aside from side-effects, MED3000 has no potential to cause adverse drug interactions, unlike oral ED drugs,” James said.
Futura is also confident that the MED3000 is effective. While a Phase 3 study showed it was slightly less effective than tadalafil, “the efficacy exceeded the minimal clinically important differences at all time points throughout the 24-week study,” James said.
The company believes that MED3000’s proven efficacy, fast action, excellent safety and lack of adverse drug interactions make it suitable for OTC use.
By contrast, PDE5is are available only with a prescription. “Aside from appealing to existing ED sufferers who treat with PDE5i’s, OTC will improve access for the large ED population who for whatever reason are not currently treating their condition,” James said.
Futura designed the FM71 study in full consultation with FDA. “As a medical device, not drug, and given the mode of action, it was determined that a placebo control in the study was unnecessary,” James said.
FDA suggested that the primary endpoint should be exceeding the threshold for a clinically important difference from baseline (pre-treatment). “FDA also asked us to run the study over 24 weeks as they had experience of ‘sham’ effects for medical devices waning after 12 weeks,” James said.
“Therefore FDA ultimately agreed that a change in 4-units from baseline at 24 weeks, using the validated IIEF-EF scale would be the appropriate measure of efficacy,” he added. A 4-unit change is widely accepted as a validated clinically important difference. “In FM71, MED3000 exceeded this threshold at all time points. At 24 weeks it achieved a 5.73 unit change meeting the primary endpoint agreed with FDA,” James said. “ There was no evidence of a drop in efficacy from 12 to 24 weeks and if anything, efficacy slightly increased with time.”