Is Xiaflex The Magic Drug
Many Hope It Will Be?
Many Peyronie's patients and health professionals have high hopes for using Xiaflex for Peyronie's disease. The initial studies have shown some promising results… but the question remains, is it enough?
Do the benefits of Xiaflex Peyronie's treatment outweigh the potential risk? Will Xiaflex injections make big difference for men with Peyronie's disease?
What Is Xiaflex?
Xiaflex is the US brand name but the generic name is collagenase clostridium histolyticum. It has been known as Xiapex in Europe. For simplification, I use Xiaflex as the common term.
Xiaflex is an enzyme produced by the bacterium Clostridium histolyticum, which dismantles collagen. FDA approved Xiaflex in 2010 for treating Dupuytren's contracture, a disorder where abnormal build up of collagen in the fingers causes permanently clenched fingers.
As you may recall, in the case of Peyronie's disease, abnormal build up of collagen in the penis forms the penis plaque. The collagenase breaks down the collagen that makes up the Peyronie’s plaque.
Will Sargent, Auxilium (manufacturer of Xiaflex) vice president of corporate communications, illustration of how Xiaflex for Peyronie's works is simple but explanatory:
“Picture, he said, the kind of long balloon that a clown blows up. Now imagine that you put inflexible tape on one side of the balloon before you blow it up. When inflated, the balloon will deviate in one direction. That's Peyronie's Disease.
With Xiaflex, he said, you inject the drug — which is an enzyme that breaks down collagen — just under the skin into the plaque at the maximal point of curvature. The drug acts like an enzymatic scalpel, he said, and the goal is to just eat away enough of that tape so that the tape breaks in two pieces and the balloon becomes straighter” (Common Health, June 2012 )
Auxilium applied for FDA approval in November 2012. FDA decision was expected on September 6, 2013 but has been postponed until December 6, 2013.
This delay is because FDA needed more time to examine the revisions Auxilium has submitted related to its risk evaluation and mitigation strategy program and the proposed product label.
If Xiaflex is approved, then it will be the first FDA approved biological therapy indicated for the treatment of Peyronie's disease.
Xiaflex for Peyronie's is injected directly into the penis and if approved, it will be available by prescription only.
The Results Of Using Xiaflex To Treat Peyronie's
BioSpecifics in collaboration with Auxilium Pharmaceuticals conducted the clinical trials. Two clinical trials (IMPRESS I and IMPRESS II) have already been concluded (June 2012) and their result is promising.
The two randomized, double blind, placebo-controlled Phase 3 studies enrolled over 800 patients at 64 sites in the US and Australia with a 2:1 ratio of Xiaflex to placebo.
The Xiaflex was injected twice a week every sixth week for up to four treatment cycles and each treatment cycle was followed by penile modeling procedure.
The average deformity of the penis at the beginning of IMPRESS I was 48.8 degrees but 31.0 degrees at the end of the 52 weeks, or 37.6% mean reduction in penile curvature. The mean reduction in the placebo group was 21.3% (from 49.0 degrees to 39.0 degrees).
The average deformity of the penis at the beginning of IMPRESS II was 51.3 degrees but 35.1 degrees at the end of the 52 weeks, or 30.5% mean reduction in penile curvature. The mean reduction in the placebo group was 15.2% (from 49.6 degrees to 41.1 degrees).
At first between 30.5% – 37.6% mean reduction in penis curvature looks quite impressive. However if compared to the reduction in the placebo group, it's less so.
Note, it is important to distinguish between the percentage improvement and the actual improvement in the penis curvature (measured in curvature degrees).
The difference in the actual penis curvature is less than 8 degrees when you compare the degrees improvement between using Xiaflex versus using placebo (substance or procedure that has no therapeutic effect, used as a control in testing new drugs).
|Impress I||Placebo||Impress II||Placebo|
So can you only expect 8 degrees better result from using Xiaflex than doing nothing? Is it enough to justify the effort, risk, time, and cost involved?
First, the good improvement in the placebo group seems to have come somewhat as a surprise. It is normally estimated that only 5 - 15% of Peyronie's cases resolve without any treatment (during the acute stage) but the result from the placebo injections were better than that.
It raises the interesting question if just injecting needle in the penis may have any positive effect on the Peyronie's plaque?
Still, most men would be pleased with 16.2 – 17.8 degrees improvement in their penis curvature, right?
Auxilium used Peyronie's Disease Questionnaire (PDQ) to evaluate the overall impact on the Peyronie's patient quality of life.
The results are somewhat surprising. The improvement in the PDQ Bother Score between the two groups (Xiaflex vs. placebo) was just about statistically significant.
Sure men felt better after having the Xiaflex treatment but not as much as you might have expected, especially if compared with the placebo group that also felt better after their pretense treatment.
Xiaflex injections are generally well tolerated but the most common side effects were hematoma, pain and swelling at the treatment site. Most resolved within 14 days.
However, if things go wrong, it can have serious consequences for the men in question. Three men (of 551, or 0.54%) experienced penile fracture or rupture that had to be surgically repaired.
There were also cases of serious hematoma cases… more about that later.
For more information about IMPRESS I and II see Auxilium Pharmaceutical Press Release .
The Bottom Line
The results of using Xiaflex for Peyronie's patients “are not overwhelming and dramatic” as Dr. Cully Carson, urologist at the University of North Carolina who was one of the trial investigators, told New York Times (June 3, 2012).
Still the main results are of statistical significance and suggest that Xiaflex may be a safe and effective non-surgical alternative for men with Peyronie's disease.
It is however important to bear in mind that Xiaflex does not cure Peyronie's disease. It is just another treatment option.
If approved by FDA then Xiaflex may replace Verapamil injections so how is...
The Results Of Using Xiaflex Compared With Using Verapamil
This is not easy to compare. There are so many different variables that can influence the outcome of Scientific Studies, as the number, age, and condition of the participants, the studies protocols, the techniques used, etc.
Various studies confirm that Verapamil can benefit some men. This study considers the ideal candidates for intralesional Verapamil treatment to:
"include those who present with pain, decline surgery, have curvature less than 90 degrees, and have a non-calcified plaque" (International Journal Of Impotence Research, 2002 )
This review of Peyronie's Injections Studies from 2007 points out that all the four Verapamil studies they found showed positive results.
When evaluated using the Oxford Centre for Evidence-Based Medicine criteria, one study was level 2, the remaining three were level 4 (level 1 strongest strength of evidence, level 5 the weakest).
The bottom line is that Verapamil may benefit some men, as will Xiaflex. Both drugs are generally well tolerated but there is always some level of risk and side effects involved when injecting any drug into the body.
Neither are miracle drug but being able to choose between more treatment options is highly valuable for men with Peyronie's disease.
More information about Verapamil to treat men with Peyronie's.
Is Xiaflex Treatment Right For You?
You should always have the same criteria in mind when deciding what is the best treatment for you and your condition.
You need to evaluate and compare the pros and cons of each treatment option available to you and especially consider the risk reward ratio.
Your conditions will also influence which options are available to you. For example, if you have severe curvature then surgery may be your only option (plus / minus 35% improvement in curvature would not be enough, i.e. going from 90 degrees curvature to 59 degrees).
Then it is the question about the cost...
Will The Price Be Right?
One of the concerns men have about Xiaflex is the price. Auxilium has invested lot of money in Xiaflex and needs to get it back.
How much Xiaflex treatment will cost is not known at this stage, but figures like $3,300 per injection have been mentioned (Xiaflex Peyronie's treatment would include 8-10 injections).
This would mean that Xiaflex treatment is not an option for the masses unless national health care providers or insurance companies will cover the cost (fully, or at least partly).
The Risk Reward Ratio Of Xiaflex
Xiaflex injections are said to be generally well tolerated but the most common side effects were hematoma, pain and swelling at the treatment site.
This is in line with what may be expected with penile injections and may be considered acceptable risk as long as not serious adverse events. In the IMPRESS I and II trials most side effects resolved within 14 days.
However when weighed against the moderate results, is it enough to convince men to go for Xiaflex injections? Is it worth the risk, effort, time, and money?
Many men will without a doubt think so. Let's face it, the options are limited and most include some level of risk, effort, time and money.
It is however important that any decision about Peyronie's treatment is an educated decision, i.e. that you research all your options carefully prior to starting your treatment.
There is no magic drug for Peyronie's now and Xiaflex will not change that. That does not alter that Xiaflex may become valuable alternative for many Peyronie's patients if approved by FDA.
Personal Experience Of Using Xiaflex For Peyronie's
As Xiaflex injections are not (yet) available to Peyronie's patients, it is not easy to find someone that has tried them.
The founder of the website curepeyronies.net participated in the phase IIb study but he received placebo treatment. However, after the trial finished he participated in the open source clinical trial that ran concurrently with the last phase III Xiaflex trial.
He has kindly agreed to share his Experience Of Xiaflex with My Peyronie's readers. It is a must read for anyone interested in using Xiaflex for Peyronie's disease.
Unfortunately, he was one of the few that experienced serious side effects, i.e. severe case of hematoma. Reading about his ordeal will make your friend cringe but it clearly emphasizes the importance of qualified health professionals and using the correct injection technique.
We owe the founder of curepeyronies.net thanks for his honest and open account of his experience and for all the valuable information on his website.
Will Xiaflex Be Approved By FDA Or Not?
We will find out soon. Many specialists seem to think it will. That Auxilium would not have put the application in without being very confident of getting it approved.
Not everyone agrees though. Adam Feuerstein, senior columnist at The Street, has thoroughly examined the available data and the way the Xiaflex studies were conducted and analyzed.
His conclusion is "no. Close, but no".
He goes thoroughly through the arguments for his conclusion but this summarizes it all in my opinion:
"Weighed against the modest efficacy, the risk profile of Xiaflex is troublesome. Even if approved, it's hard to envision scenarios under which the drug is widely used in men with Peyronie's" (The Street 08/26/13 )
This was written couple of days before FDA announced three months delay in their decision. It will be interesting to see if this will affect Adam Feuerstein conclusion. I strongly recommend reading the whole article, very informative read.
Not getting FDA approval would be serious blow for Auxilium and those that have pinned their hopes on Xiaflex for Peyronie's disease.
But time will tell, we will hopefully find out before the end of this year and I will keep you posted.