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      XIAFLEX - Is It The Magic Bullet?








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?
 

End of Xiaflex article.