Dr. Hellstrom, Professor of Urology and Chief of Andrology at Tulane University School of Medicine in New Orleans, is one of the principal investigators involved in studies of avanafil, an investigational phosphodiesterase-5 (PDE-5) inhibitor that in phase 3 trials has demonstrated efficacy and potential advantages over other PDE-5 inhibitors. In an interview with Renal & Urology News, he discusses avanafil and PDE-5 inhibitors in general.
How does avanafil differ from other PDE-5 inhibitors?
Dr. Hellstrom: It works by the same mechanism, but there are slightly different pharmacodynamic and pharmacokinetic aspects of this compound that may be advantageous to patients who are being treated for erectile dysfunction (ED).
The potential advantages are that it’s more quickly absorbed. That means that a sizeable number of patients who are being treated for ED will be able to attain a satisfactory erection in a shorter period of time. Many patients were successful in the first half hour, more so than the other PDE-5 inhibitors. Sildenafil, vardenafil, and tadalafil have done extremely well and are considered first-line therapy for ED, but there’s room probably for a little differentiation and improvement on the drugs we have right now.
Avanafil is a bit more selective in its action, so there are lower instances of back pain and visual and hearing disturbances. There was a low discontinuation rate in long-term studies.
The faster onset of action and an attenuated adverse event profile, may make this form of a PDE5 inhibitor advantageous to many patients.
Does avanafil show efficacy in some patients who do not respond to other PDE-5 inhibitors?
Dr. Hellstrom: No. What we found is that when patients don’t respond to a PDE5 inhibitor, a lot of times they just need to be educated and to up their dose and not to eat fatty foods with these medications and to be stimulated sexually.
There’s a large psychological component of any kind of sexual dysfunction and it’s surprising that some patients see a certain medication that’s advertised and come in and say I want to try that medication. They just believe that this medication will work better for them.
There are idiosyncratic episodes where one medication works better for a different person. By and large, if you were to take the same person, under the same conditions, and if he had no response to one of the other three, I would not expect a person to respond with the avanafil over the other three. However, there are small issues.
For example, the quicker onset of action may be very important to some people. And the fact that there is an attenuated adverse event profile may be appreciated by more people, and prompt them to select this medication.
What proportion of men is helped by PDE-5 inhibitors?
Dr. Hellstrom: Somewhere between 40% and 70% of men who use PDE-5 inhibitors will benefit, but this still leaves a large group of patients who are not responsive: certain men with severe ED, diabetics, those who had a radical prostatectomy, and patients who have had transplant surgery, where the vasculature has been disrupted will probably not respond well or at a high rate with PDE-5 inhibitors. For men who have mild ED or are taking medications for hypertension or antidepressants, these men do respond quite well, and obviously men who have psychogenic ED respond well.
What new approaches to ED therapy do you foresee?
Dr. Hellstrom: We have found that many men who did not respond to PDE-5 inhibitors did so when they were placed on testosterone replacement therapy if they were hypogonadal. It is important to make sure men are not hypogonadal before starting PDE-5 inhibitor treatment. Combination therapy with a PDE-5 inhibitor will probably be the next great breakthrough as far as capturing some of the patients who don’t respond to monotherapy.
Have PDE-5 inhibitors put a dent in surgical caseloads for ED?
Dr. Hellstrom: A lot of concern in the 1990’s was that if a pill came out, your surgical therapy caseload would disappear. If anything, the opposite has happened. The availability of PDE-5 inhibitors brought many men in for treatment. Some 20% to 30% of those who did not respond to the treatment went on to more advanced treatments, including surgery, direct injections of vasoactive drugs into the penis, and vacuum devices.
What other aspects of PDE-5 inhibitors would you like to emphasize?
Dr. Hellstrom: The introduction of PDE-5 inhibitors may have resulted in increased screening for cardiovascular problems. Many men with ED may have endothelial dysfunction or cardiovascular disease. There are a number of studies showing that a high proportion of men with ED will develop a cardiac or some kind of vascular event within the next few years.
A good physician doesn’t just write a prescription for PDE-5 inhibitor. He will look to see if there are risk factors that can be corrected, which may prevent mortality and morbidities such as stroke or heart attacks at a young age.