The most common topic of emails I receive for this site is Xiaflex. Readers of this site have referred to as the The Magic Bullet or The Wonder Drug and The Cure. Unfortunately, none of these superlative descriptions accurately describe the clinical trial outcomes conducted by Auxilium Pharmaceuticals to determine the safety and efficacy in treating Peyronies Disease with Xiaflex.
First let me say,
I have had a very long term interest in investing, particularly in the stock market. The majority of stock market sites I read predicted that Xiaflex would not be approved because of its limited efficacy and potential for serious adverse reactions. I reasoned correctly that men are so desperate for a treatment for Peyronies that the FDA would approve the drug.
I have written a great deal about Xiaflex in prior editions of this site, but it appears many men have not bothered to read my detailed reports on the clinical trials and my personal experience with this drug. Everything you have read on the Internet about Xiaflex is nothing more than public relation releases or information related to much abbreviated clinical trial abstracts. What makes this site unique and in my humble opinion, most valuable, is that I go to the trouble and expense of obtaining the complete reports published in scientific journals.
Xiaflex has objectively demonstrated limited to moderate success in alleviating some of the symptoms of Peyronies Disease for men who participated in the clinical trials. It is not a cure, but it is the only non-surgical agent that has demonstrated efficacy in relatively large, blind, placebo controlled clinical trials. That is the extent of it and each man must make up his own mind as to whether it is worth the risk, time and money to be treated with Xiaflex.
For those of you who have kept current on this topic some of what I will be writing on this page will be familiar. Some material you will have not seen unless you have obtained access to medical journals. If I have any comments, they will be italicised. After this article, I hope not write about Xiaflex for some time because I am simply summarizing most the same findings again and again.
Let's start with a summary of the findings: In an earlier phase of the study it was reported that 61% of men who were injected with Xiaflex met the goal of at least a 25% reduction in curvature. To everyone's surprise 25% of the placebo group who were injected with a saline solution also met this curvature reduction goal. This was a surprise to all researchers and Auxilium hypothesized that is was due to age difference between the placebo and Xiaflex group. I don't buy this explanation and no one really knows how to explain this outcome.
In a more recent report which appeared in the Journal of Urology and which discussed combined study results for both phases of the clinical trials:
Mean curvature of 53 degrees
Xiaflex treated men showed a 34.4% improvement -17 degrees of curvature plus or minus 14.8 degrees
Placebo group had an 18.2% degree improvement - 9.3 degrees, plus or minus 13.6 degrees
Prior treatment history made no difference in outcomes
Baseline curvature made no difference in outcome
Do not forget! The primary results that you may read about in various sites and abstracts is not in absolute degrees of improvement, but percentages of improvement. So, when clinical trial participants have a mean curvature of 53 degrees and demonstrate a 34.4% improvement, the actual improvement in degrees in 17 degrees.
In early December 2013, the FDA completed their review of the above clinical data and approved the use of Xiaflex to treat Peyronies Disease. The drugs use is restricted to the Risk Evaluation and Mitigation Strategy (REMS). Treatment should be limited to those health care professionals who have experience treating male urological conditions. These health care professionals must be certified that they have been trained in use of this drug to treat Peyronies. Men have written me asking when they can start treatment. If you are hoping to have insurance companies pay for this treatment, you must wait for their approval and that depends on the individual insurance company. Guess this will not be completed until around August 2014.
Here is where is gets interesting and we maybe getting some new information or at the very least some new and important questions are raised. Just as a reminder, my comments will be in italics.
The Journal of Urology published a letter on the topic of the Xiaflex clinical trials from the Department of Urology, Chandgarth, India which raises a number of interesting issues.
The ecchymotic lesions (hematoma) when healed may form new plaques.
StudIes showed a significant mean improvement for Xiaflex vs the Placebo of approximately 17 degrees. This improvement would result in a final curvature of 43 to 53 degrees.
This resulting curvature would still preclude normal sexual intercourse.
The authors of the original article that appeared in the Journal of Urology responded with a defense of the use of Xiaflex for Peyronies Disease and the clinical trials conducted by Auxilium Pharmaceuticals. They made the following arguments:
Serious adverse events were limited to 3 penile hematomas and 3 ruptures of the tunica albuginea.
I am glad they considered a hematoma as a serious adverse events. In other reports I have seen only the ruptures were classified as serious. As someone who did experience a penile hematoma as a result of a Xiaflex injection, it is a serious event. More importantly, these authors failed to speculate as to why these serious adverse events occurred. Was it due to the urologist not being careful or following protocol, or are some men just more sensitive to the drug than others or does it have to do with the nature of Peyronies plaque? I wish the authors said something. Then again, physicians usually do not criticize other physicians, particularly via a public medium such as a medical journal.
Subjects who received injections Xiaflex and experienced bruising did not experience development of additional plaques.
Oh really! As one of the men who did develop a hematoma after a Xiaflex injection I can speak from experience. After developing the hematoma I was examined by the clinical trial urologist either one or two times. But I was never examined after the hematoma started to shrink significantly or after it disappeared - about a year later. Consequently how would they know I did not develop any additional plaques?
The standard deviation of penile curvature outcomes was fairly wide and at the end of the study most investigators could identify results from disappointing to amazing. Several factors may contribute to the observed variability in curvature correction. In some subjects severe angulation results from an elongated, but relatively narrow band of scarred tunica, while others may have the same angular deformity, but with thick, wide dense plaque like areas of scarred tunica. It appears that Xiaflex can only dissolve a certain amount of collagen at the injection site. One of the best study results were demonstrated in a man who had a long, linear cord-like plaque. After the Xiaflex injections he went from an almost 80 degree curvature to 14 degrees.
This is extremely interesting and new information which I have not seen published anywhere else. If the structure of the plaque can predict results of the Xiaflex injections, why isn't there more information available. For those men who want to receive the injections, they may wish to discuss this plaque physiology with their physicians. The authors conveniently fail to address the issue of why there was significant curvature improvement in the placebo group. They also did not address the issue of whether any men in the study had an increase in curvature. If you are man with an elongated, relatively narrow band of plaque, maybe saline injections should be tried before Xiaflex? Could it be that the needle itself causes the improvement in men with certain plaque characteristics?
I was correct in my prediction that Xiaflex would be approved for the treatment of Peyronies Disease. Here is another prediction. The roll out of Xiaflex for Peyronies Disease will not go smoothly. Men are so desperate for a non surgical treatment they will not do the proper due diligence about their urologist before obtaining treatment. You want a Tier 1 urologist who specializes in the treatment of Peyronies Disease! Or else you are asking for trouble.
Do yourself a big favor. Carefully read all the article I have written in prior additions of this website. My experience with Xiaflex did not go well and believe me, you want to do everything possible to avoid repeating my experience. For prior articles on Xialfex Click Here And Click Here .
There is one more aspect of all these Xiaflex studies that raises a question in my mind. Another journal article reviewed in much detail the pre-treatment baseline characteristics of men in the Xiaflex studies. The mean age was almost 58 years, they had Peyronies for just over 4 years and a mean penile deformity of 50.5 degrees. They reported having vaginal sexual intercourse slightly more than 2.5 times per week. Is it just me or given these baseline characteristics does 2.5 times per week seem unrealistic?