Developmental drugs & treatments - Still in trial or not approved for Peyronies

[ohjb1]

RBWoodward - In answer to your question about receiving the placebo, cute and paste htttp://www.curepeyronies.net/index05Xiaflexupdatel.html

[Hawk]

Ohjb1,

If you have a response from the xiaflex trial you want to cut and past on this site then feel free to do so.  

This is the 3rd link of your website you have posted on this forum.  As I recall you came here asking for money 30 minutes after you registered on this site.  This link may refresh your memory. https://www.peyroniesforum.net/index.php/topic,639.msg12192/topicseen.html#msg12192  
I suggest you read the entire topic if you have not done so!

You are getting very close to the point of looking like you are making unethical use of this site to promote your own activities.  If you have any legitimate intentions you would not be spamming other sites and proceeding as you have done up until now.  As a website owner you surely know proper internet etiquette for posting your links on other sites especially repeatedly posting them.

In case I have been too vague up until this point, your conduct is now resulting in an official public warning.

Hawk

Administrator  

[ComeBacKid]

Ohbj1,

It is suspicious activity like this that leads one to say hmmm " Does this guy even have peyronies?"  "Is he really in the xiaflex treatment study?" This is why we will have to wait for the final report on the clinical trials and trying to get answers off here may not be the best idea.  

[McNally]

First, yes, I'm in the study. Because of postings I've read here, I made a point of confirming during my last visit (3rd round injections) to Dr Levine's office that placebo recipients will be offerred the opportunity to recieve the drug in the future. Further there is language in the consent form I signed that people that receive the placebo may be asked to be in another study where I would assume they would get the drug. I hope this information helps any participants that were feeling anxious about this aspect of the study. We are doing a good thing by being in this study, and as many have posted it hasn't been easy.

[McNally]

I have just finished reading the last month's worth of postings & I guess I could share my Xiaflex study experiences. I am 57 years old & I guess this all started a few years ago. To tell you the truth, I no longer remember if my onset was gradual or sudden, it just seems like it's been forever. I have around a 70-degree curvature with the "hour-glass" deformity. The plaque runs almost the entire length of the top of my penis, with a major nodule or two at the base. No erectile pain or pain during intercourse, though some sensation of "blocked" ejaculation. I feel I've had a major decrease in penile sensitivity, though I understand this could be a psychological side effect. I feel I need to use Viagra to maintain my erection during attempted intercourse and avoid "hinging". All this, along with my wife's normal age related sexual issues (decreased lubrication, dropped uterus floor), results in major impediments to penetration and sexual enjoyment. Masturbation is difficult because of the bend, but possible (especially with assistance of a soft flexible masturbator). I became a patient of Dr. Levine's because of his reputation with this disease and to get into this study.

Let me preface my description of my experience with the qualification that not everyone is going to have the same reactions, so don't read too much into this. I had my 3rd round of injections around the holidays. I don't know if this idea of reactions getting worse with each round is valid, but I can say I had my worst reaction after the 3rd round. Lots of bruising that then "dropped" into my scrotum   and pain (this was the only round I ended up using an ice pack!). But I can also say I was distracted by a conversation during this round and was not paying full attention to applying pressure to the injection sight (wish I had read that tip earlier   ). I am part of the modeling group. The modeling done in the doctor's office was painful, though I haven't needed to request a pain blocker. The modeling I do at home is not bad at all, bending while erect & pulling/stretching (though my wife says I've had my hand in my pants way too much   hey I'm just trying to follow instructions). I read with interest the comment about the severe bending that was/is part of the Dupuytrens Contractures treatment. That sort of coincided with another comment I read a while ago someplace that stated that men who re-injure their penis have a better chance to recover from Peyronies Disease. (Also thanks to "Old Man" for Lederhose reference - hadn't heard of that & think I have that - I'll have to mention at next visit.)

Before I mention any results, let me remind everyone that 1) I have no idea which group (drug/placebo) I'm in & 2) anyone who has seen significant improvement is probably not posting on this board, they're probably off enjoying a return to normalcy   That said, I think you can guess I've seen no improvement. However I think we need to remember that this study is not only about the drug, but the effectiveness of this course of treatment. It may turn out that the drug works, but needs to be administered differently in certain cases. I am still hopeful and positive about the drug. Hey, if this works, it's probably the best alternative available, but no one's going to know anything until they publish the results & that's a ways off. Unfortunately there is not going to be a definite answer tomorrow or next month or probably even this year. We need to be patient.

Finally, a comment on the comments about the surveys we're filling out. This is a necessary step in validating these questionnaires for future use in evaluating Peyronies Disease cases and helping doctors establish appropriate courses of treatment. They are not a waste of our time in any way, even though it may seem that way. It is a separate study from the drug study in my understanding.

[bones54]

Update.

Now 4 days after 2nd injection of 1st series.  Swelling is better but still localized around base of penis and pubic area where marcaine was injected.  Still quite sore to touch.  Hard to tell what has happened to bend with erection as swelling is masking true shape.  It seems as though I'm...shorter.  I'm totally in denial though...willing to pass judgement when swelling is all gone.

Not sure if 6 weeks between injections will be enough to forget the pain.  Local didnt work on second shot and even though volume of injection is tiny..and needle is tiny...it killed.  What we dont do for science.

[bones54]

has anyone else reached the last stage of injections?

[MUSICMAN]

If you go to the Auxilium website they report that Trial llb sign up is complete and all have had their first series of shots. They expect the results of the study my the 4th Quarter of 2009. Phase lll will not be expected to start until the middle of 2010  -   Yes mid 2010.  As I read the news report it looks as if Phase lll will use the Drug / Placebo in the study. My question is how are the one in the llb study group that received the Placebo be first in line to get the real drug and not the placebo again in phase lll

I don't think the drug will be used except in the Study Trials.

[Iceman]

forget xiaflex - its too far down the track - it will never happen - stick with the ved and pentox - thats the reality and thats all there is to it!!!!!

[Tim468]

Musicman - when a trial closes, it means that recruitment is over, not that data collection is over. The people just enrolled will get their injections over time, and be followed up, such that all should be done by the fall. Then getting that data collated and presented such that approval is forthcoming from the FDA for the next step takes time!

It is moving forward, at least.

Tim

[Hawk]

forget xiaflex - its too far down the track - it will never happen ... thats the reality and thats all there is to it!!!!!

Iceman,

That is one absolute statement to be throwing out.  Are you sure you would not like to qualify that statement.  If you are willing to wager big bucks on that, then provide your case.

[Iceman]

its just a gut feeling hawk - no cure for the past 250 yrs why would there be one now - plus im just venting frustration at the whole bloody thing!

[Believer]

Sometimes reading posts like the one below makes me want to pinch myself to see if I might be having a nightmare...

Iceman, for the next 2 years, we must be overly-optimistic. Let the trial run.

Why can we expect a cure? Well, for one thing - technology today never existed not just 250 years ago, but try 15! And if you recall, in 1992 or so, Verapamil was discovered. Yes it barely works - but still! Before Verapamil - people were limited to Vit. E!

Also - another reason for hope is globalization. Peyronie's is not just 1% of men now. It's more like 10% as more and more people speak up on forums like this one. 10% of the world's population of men is a lot!

Globalization allows doctors all over the world to exchange ideas easily. Levine, Lue and others are flying to Europe for lunch-and-learns and vice versa.

Human effort is the cure for Peyronies. Collagenase makes sense. I think we should remain optimistic. If nothing makes you feel better, consider this: if you it hits the fan - at least you have some hope. In less than 2 years you will know whether Xiaflex works. Only 5 years ago, people didn't even have that option.

Let's stay optimistic and focus on outreach. This forum needs to grow.

[jackp]

Iceman
I feel your frustration. But, we have to believe in progress. Myself at 66 people asked my why I opted for an implant, in just a few years there will most likely be a cure for ED. My responce was I don't have 10 years to wait.
If I was a younger man I would be right in the middle of any trial for this dread problem. For those in the trial I offer my support and well wishes.
Jackp

[j]

Looks like Intermune will be seriously marketing Pirfenidone.  Their original competing drug - Actimmune - bombed in trials.  

http://www.nytimes.com/2009/02/04/business/04lung.html?ref=business

[roadblock]

Two comments regarding the article posted by j on Pirfenidone:

1)  I couldn't help but notice that Viagra is being studied for the treatment of IPF. This leads me to believe that the value in a daily dose of Viagra or Cialis lies not only in the improvement of the ED but in the anti-inflammatory properties of the drug! This may also lead to strengthening of the association of Peyronies Disease and IPF as people from both sides explore possible treatment ideas.

2)  Notice that Actimmune was largely prescribed off-label, and that this was a fairly accepted situation since there were no other treatment options. As the years go by, and pirfenidone (hopefully) builds momentum as well as a favorable side-effect profile, we may see doctors more willing to prescribe pirfenidone off-label for Peyronies Disease. The difference being that Peyronies Disease is not a life or death situation, no matter how distressing it is psychologically.

I'd also like to echo the sentiment towards the study participants that others have posted. I look forward to your accounts of what you are experiencing and what you are hearing from the urologists. Even though we have not seen much in the way progress YET, I'm still very hopeful and thankful for those of you sticking it out. Keep the info coming!

roadblock

[Hawk]

Roadblock, you make some good points on the Viagra connection.

Was this an intentional pun?

I'm still very hopeful and thankful for those of you sticking it out.

[alcohen]

Iceman
If I was a younger man I would be right in the middle of any trial for this dread problem. For those in the trial I offer my support and well wishes.
Jackp

After visiting 1 hateful GP, 2 hateful Uro's, and 1 uro who refused to give me anything besides "good luck" to help me I am disgusted with the whole thing.  Are there any trials for venous leakage treatment?  It appears not.  Obviously I do not have simply venous leakage though and those of you who have followed my posts know that to be the case as well.  Sometimes it feels like the pain will never be gone and I wonder about my future.  I can't get involved in any study or anything that even has a chance of helping me because my doctors refuse to diagnose.  Has anyone here been to Dr. Culley Carson and been given any other treatment or recommendations other than Trental and to wait?  As my erectile dyfunction continues to worsen I am left with a sick and bitter taste in my mouth towards all the doctors I have seen over the last 8 months.  

[Vernon21]

I've finishied all three series and wanted to report back to the group once things settled down and I had an idea of where I stood.  Long story short I reduced the bend (more like angle for me) about 10% 10 degrees (corrected per writers later correction - hawk).  I would be real surprised if I didn't get the real stuff.   I had hoped the plaque would just melt like a pat of butter but it didn't (totally anyway). Still I think the glass is half full and Xiaflex is a good thing. I'm guessing I could probably benefit further with a few more series and I will definitely persue it when the approval comes for Dupuytrens.  There will also be much learned how to optimise the treatments once all the data is in. I also think the drug company is mainly trying to show improvement without side effects and get the drug approved.  Based on my experience, if I could pass on one thing it would to be optimistic but realistic. The success with Dupuytrens may not bring the same results with our disease. With Dupuytrens all they are doing is breaking a cord and stopping it from growing back.  Peyronies involves more vital tissue and may be more like getting glue out of a sponge than just cutting a cord.  I'm hearing others in the trials are making progress on reducing their bend but no miracle cures.  I've also heard Xiaflex will do more to help a bend then a dent condition.  It is not expected to help calcification.  The injections also caused more of mental roller coaster than I expected. I'm pretty level headed but with all the bruising and swelling it was a little taxing wondering how things were going to turn out. I also had some swelling that caused me to think I made more progress than I did.  You really need to wait at least 2 weeks before you have an idea if you made some progress.  Keep in mind this is just my experience (everyone is different) and some unofficial feedback I've heard.  I would encourage others to post but we should not draw any final conclusions until all the data is in.  Hope this helps.

[shrout]

Peyronies involves more vital tissue and may be more like getting glue out of a sponge than just cutting a cord.  

I like this description of Peyronies... glue in a sponge... although I wonder whether it's totally accurate. In Peyronies doesn't the glue replace the sponge rather than just get inside it. So once the glue is removed there's nothing left?  Hopefully I'm wrong, but maybe someone more qualified can clarify this.

Anyway, good to hear of your progress Vernon, and thanks very much for reporting back so eloquently.

[Hawk]

I think Vernon made several good points and I agree with his point that Peyronies Disease may be a more complex issue to resolve than DC.  I do think that typically the sponge analogy is a bit off.

Generally, Peyronies Disease is not scar tissue through the corpus Cavernosum or spongy tissue that engorges with blood. It is scar tissue on the sheath (tunica).  Because the sheath scaring cannot expand the sponge inside cannot expand, not vice versa.

[George999]

Actually, I think Vernon is on the mark with his glue in a sponge analogy as long as one understands that the tunica, not the corpus, is the sponge, a sort of condum shaped sponge.  Glycation works just that way.  It causes tight disorganized crosslinks to form in the tissue making it stiff and inflexible.  These crosslinks are formed out of protein and this is the structure that Xiaflex must dissolve.  I also agree with Vernon that Xiaflex will not be a turnkey solution.  It will be just another tool, a good tool, but not a complete solution.  As for calcification, we already know that there have been multiple successes with Trental.  So that base is already covered.  The bottom line is that even with the strong headwind that is blowing in our direction in terms of Peyronie's research, progress IS being made and there are DEDICATED professionals out there giving it all on our behalf.  Personally, I believe that at some point alagebrium is going to get approved and also be picked up eventually by some Peyronie's doc for off label evaluation.  Alagebrium is an oral treatment that performs something of the same task as Xiaflex, although not as dramatically.  But it IS systemic in nature which will offer yet another approach to a sticky problem.  - George

[j]

I think Vernon21 is also right about Auxilium setting the bar low. They need to show only enough improvement to get approval, without unexpected side effects that become deal-breakers.  So the treatment might be conservative. There are also limitations on time and money, so they probably can't run a long series of small injections, for example.  

My Peyronie's is 'manageable' and actually I have a more urgent need for Dupuytren's treatment at this point, so I'll be seeking out a hand surgeon to hit me with Xiaflex as soon as it's available.

With DC, you can get rough.  People in the Xiaflex trials for DC talked about the audible "pop" when the MD snapped the cord - and in some cases the very audible yell of pain that followed.   Peyronie's will require a more sophisticated technique but we now have an agent which breaks up this collagen, surely there will be a way to use it more effectively than what is being done in these early trials.

[shrout]

Hawk, I understand what you are saying, but what's not clear in my mind is whether the scar tissue in Peyronies is additional tissue which has attached itself to the tunica, or is tunica tissue itself which has, by whatever process, turned into scar tissue.

If it's the former, once the scarring is removed the penis should, in theory, return to normal function. If the latter, once it's removed, by surgery, or Xiaflex, or whatever, surely there would be areas where there is no tunica, which I presume could  lead to further problems i.e. leakage from the corpus Cavernosum, leading to ED, for example.

I may be way off the mark with my suppositions here, of course.

Apologies if this question has been answered elsewhere on the forum. I've had a look around and can't see anything.  

EDIT: I guess George has partially answered my question. It's still not clear though how viable the remaining organ would be once the scar tissue has gone, if there is no tunica either.  

[George999]

Shrout,  Xiaflex is actually just a trade name for collagenase.  You can look that up in Wikipedia.  Collagenase is the same substance the body produces to prevent the uncontrolled proliferation of collagen.  It doesn't "dissolve" the scar tissue, it "corrects" it and once its "corrected" by having the abnormal tight crosslinks removed, it normalizes itself and, to the degree it normalizes, resumes its usual thickness and suppleness.  People get confused by the fact that in the case of Dupuytren's, the "cords" need to be "snapped".  This is only because Xiaflex only partially does the job.  If Xiaflex were to do the job completely, there would be no need to "snap" the "cords" because there would be no remaining "cords" to "snap".  So we are talking about normalizing tissue by supplying collagen externally that the body is failing to provide on its own.  There is no danger of melting away the tunica, but there might be untoward side effects from injecting too much collagenase although I don't know what they would be or even if the researchers know what they might be at this point.  I too agree with Vernon.  These docs are starting out VERY conservatively, because they would much prefer partial success to show stopper side effects.  Once its approved, they are likely to get more aggressive and persistant.  - George

[ComeBacKid]

Hawk is dead on and its good the scar tissue is on the tunica and not the corpus. If the tunica eventually totally becomes scar tissue the full penis size can not be realized in erection, but if this tissue is eventually disolved or reversed you can get your length back in theory.  If the corpus turned into all scar tissue, it wouldn't expand at all and there'd be nothing to expand....  

[McNally]

Have any of the study participants thought about what they're going to do next? As I've said elsewhere, I fairly sure (or at least very hopeful) that I got the placebo. BTW, Vernon21 congrats on seeing some improvement. If I read you correctly, I strongly agree that future treatment protocols with Xiaflex are a long way from being established. I think we'll see a much more aggressive treatment plan once the drug is approved.

Anyway, I was thinking I'll probably wait for the next study phase where I assume I'd be offered the drug, but that might not be for a year or more, right? I'm also afraid that if I tried any other treatment options, I would disqualify myself from future Xiaflex testing.

McNally

[Vernon21]

For me, I hope to hear more from others.  While I think myself and others may benefit from some more Xiaflex injections, it still seems best to wait until all the data is in.  I may not qualify for the open label trails but it is also quite possible that Xiaflex will be approved for Dupuytrens first. When that happens I will seriously discuss further treatments with my doctor (who is very experienced) on an off label basis.  I am getting conflicting information if the first approval for Xiaflex is expected to be in Europe/UK or US. Has anyone heard anything more definite on this?

Also, in my earlier post perhaps I should have said "glue around a sponge" (maybe a bad analogy altogether).  No need to belabor it, the point being I think there are more complexities to treating Peyronies tissue with Xiaflex than Dupuytrens tissue.

[Believer]

Vernon,

Was that a 10 percent or 10 degree improvement? Also, who was your doctor?

Thanks

[Vernon21]

It was 10 degrees, sorry for the error if I mistated it.  I don't mean to sound cagey but until I am totally finished with all the required follow up, I would perfer not mention my doctor just yet.  He is well known as an expert in this field.

[Believer]

Vernon,

No worries about the doc.

10 degrees is much better than 10 percent. I really hope that this thing hits the markets soon.

[Vernon21]

Thanks for asking so I could clear that up for everyone. I had an approximate 10 degree improvement not 10%.  Must have been too focused on typing the message and had the wrong calibration stuck in my head. Sorry for any confusion.

[UK]

Vernon - out of interest what was your starting point in degrees and I take it you were in a non-modelling group? Thanks

[Vernon21]

I was in the modeling group.  I was closer to the lower threshold, 30 degree bend, required to qualify for the trails than the higher threshold which I think was 90 degrees.

[ocelot556]

Just thought I'd chime in to mention... it seems as of January 12th, Synvista has completed enrollement in it's Phase II trials for Alagebrium. This is great news. We can all keep our fingers crossed this works - although they're measuring for heart-related diseases, this will surely open the doors for ED testing, a field which Synvista has already held trials for with this same product! Xiaflex isn't the only treatment coming down the pike...

[Tim468]

Just a random note on doing a trial...

Thinking about it (always a dangerous thing for me...), it seems that a variable in this study (Auxilium) is that A) the skill with which the plaque is injected may vary, B) the technique with which the modeling session is done by the Uro may vary and C) the techniques for modeling/stretching done by the patients may vary.

I suppose that if enough patients participate, that this should come out in the wash - should even out across centers. But a sub-analysis worth doing would be to see if there were any trends towards improvement by doctor, instead of by treatment. I hope they do that sub-analysis.

Tim

[Tim468]

I have mentioned more than once how much I wish that we had a form of advocacy as potent and lively as the Cystic Fibrosis Foundation. This was started by the families and patients with CF, not by doctors (this is vital to remember) and they have help advance the cause of CF research greatly. How much I wish Peyronie's Disease had such a focus of funding, energy and institutional cooperation!

The messages we use to help remind patients as to why it is important to participate in clinical trials are pertinent to those of us here who have the opportunity to participate in such trials. I kow how frustrating it is to worry that one might be getting a placebo, but there are other compelling reasons for participation.

This is a good friend of mine talking about the research doctor's perspective, and why it is so important to those of us who do research that patients participate in trials.

http://www.youtube.com/watch?v=eMgaCbAN0K4&feature=channel

This is Boomer Esiason talking about the same thing, from the perspective of a father of an affected child

http://www.youtube.com/watch?v=do2KyqU6J4Y

Finally, here is a clip of a young girl herself. I hope that these clips serve to remind us why doing science is important, and why we must try to work together to lick this disease, er, beat this disease, er, dang!... well, you know what I mean!

http://www.youtube.com/watch?v=FxyxWJcw4rA&feature=channel

Tim

[George999]

I certainly agree with what has been already said on the drug trial issue.  In the case of both Xiaflex and Alagebrium, I believe the best shot here is just getting these drugs out the door in the first place.  At that point, the owners of these drugs will be able to get them on the market and start to recoup their initial investment.  Then there will likely be further trials and studies to refine treatment approaches AND explore new applications.  Remember, once a drug is approved by the FDA, it really doesn't require a full blown trial to extend its applications and refine treatment approaches.  Its safety has already been subject to scrutiny and the door is opened to judicious off label use.  That is a major reason that companies are so conservative and risk averse in their initial trials.  They just want to get their product on the market in the first place.  AFTER THAT, their product can bloom and take root.  Anything WE can do to get those innovative products over that initial hurdle will likely pay us all significant dividends in the future.  Of course it would be nice to have a foundation at our disposal as well, but I think that many of us underestimate the value of this community and also of the professional community of which Drs Lue and Levine are a part.  I think this actually gives us a leg up on some other very worthy patient groups that unfortunately are suffering irrelevance even worse than what we have to put up with.  In the economy of this world, having any kind of "rare" disease is often a death sentence.  Even though the cure my be relatively simple, no one is willing to put forward the capital to make it happen.  Sad ...   - George

[bones54]

quick update..going to have second round of xiaflex injections in 2 weeks...do not see any improvement...if you had me make a bet, I got the real thing...but maybe i should be hoping I got the placebo.

[j]

With regard to getting public support for research - CF affects the lungs of young children.  Peyronies Disease affects the penises of older men. End of discussion.

I agree with George999, and hope he's right.  Just injecting some Xiaflex into the plaque, somewhere, doesn't seem to be very effective.  In my imagination I see some sort of time-release capsules embedded under the skin, releasing collagenase steadily over time.

[ComeBacKid]

"Just injecting some Xiaflex into the plaque, somewhere, doesn't seem to be very effective"

J,

Don't you think that statement is a bit premature?  We are going based off of what people on this forum are telling us, and they don't even know if they have placebo or not?  I to share your skepticism, on the other hand we didn't go through the full trials with a report yet.

Comebackid

[j]

You're right, it's too soon to say anything,  especially if the injection causes temporary bruising and swelling.  I still think this stuff will work for Peyronies Disease because it's already working for Dupuytren's.   What I should have said was that a simple injection may not turn out to be the most effective way to use it.

[George999]

Sometimes one just has to dream.  According to this paper,

Previous reports have indicated that inflammatory mechanisms may be involved in the pathogenesis of Dupuytren's disease and it has even been suggested that this condition is a T-cell-mediated auto-immune phenomenon.  Gudmundsson et al investigated subsets of peripheral blood lymphocytes from 21 patients and compared them with those of ten healthy blood donors and found that the Dupuytren patients had an increase in DR+ T-cells when compared with the control group.  They considered that these findings support previous suggestions that immunological mechanisms, involving activated T-cells and probably also B-cells, are involved in the pathogenesis of Dupuytren's disease.

What a fascinating little piece of information.  The probability that B-cells are involved in Dupuytrens's and, thus, probably in Peyronie's as well.  IF that be the case, one has to wonder what might happen if a Peyronie's patient were treated with a drug that knocks out B-cells.  A drug such as the mono-clonal antibody Rituximab.  I wonder!  - George

[jon]

Sometimes one just has to dream.  According to this paper,

Previous reports have indicated that inflammatory mechanisms may be involved in the pathogenesis of Dupuytren's disease and it has even been suggested that this condition is a T-cell-mediated auto-immune phenomenon.  Gudmundsson et al investigated subsets of peripheral blood lymphocytes from 21 patients and compared them with those of ten healthy blood donors and found that the Dupuytren patients had an increase in DR+ T-cells when compared with the control group.  They considered that these findings support previous suggestions that immunological mechanisms, involving activated T-cells and probably also B-cells, are involved in the pathogenesis of Dupuytren's disease.

What a fascinating little piece of information.  The probability that B-cells are involved in Dupuytrens's and, thus, probably in Peyronie's as well.  IF that be the case, one has to wonder what might happen if a Peyronie's patient were treated with a drug that knocks out B-cells.  A drug such as the mono-clonal antibody Rituximab.  I wonder!  - George

so who wants to give that a shot?

[jon]

Along those same lines, what about something like Orencia as well?

T-cell Costimulatory blockade
Abatacept (Orencia®)
Abatacept is the first of a class of agents known as T-cell costimulatory blockers.  These agent interfere with the interactions between antigen-presenting cells  and T lymphocytes and affect early stages in the pathogenic cascade of events in rheumatoid arthritis.  T lymphocytes become activated due to an unknown stimulus but likely involving the interaction between antigen presented in the context of the Class II Major Histocompatability Complex molecule on the surface of antigen presenting cells. T cells recognize antigens as foreign and if they receive a second stimulus, will become active, proliferate, traffic to inflamed sites, and secrete proinflammatory cytokines including TNF. One of the important second signals for T cell activation is mediated by the molecules CD80 and CD86 found on antigen presenting cells and the CD28 molecule on the T cell surface.

Mechanism of action:

Abatacept is a fusion protein that combines the extracellular domain of the  molecule CTLA4 (CD154) with the Fc portion of a human immunoglobulin molecule. CTLA4 has very high affinity for CD28. When abatacept binds to CD28 on the T cell surface, it prevents the second signal from being delivered, thus turning down the T cell response. Additional effects are decreasing the production of T cell derived cytokines including TNF.

Dosing:

Abatacept is administered via intravenous infusion once per month after initial doses at baseline, 2 weeks, and 4 weeks. The dose is based on body weight, with patients <60 kg receiving 500 mg, 60-100 kg receiving 750 mg, and >100 kg receiving 1000 mg.  The medication is administered over a period of approximately 30 minutes to one hour.

Time to Effect:

Responses are typically seen within 3 months.   In clinical trials, patients with initial responses continued to show improvements through the first year.

Adverse effects:

As with other biological DMARDS infections are increased in patients receiving abatacept. These have ranged from mild to severe.  Respiratory infections including pneumonia were more common in clinical trials in patients with underlying COPD, thus extreme caution is suggested in this population. Malignancies have been seen in clinical trials but it is unclear if the rates are more that expected in patients with rheumatoid arthritis.

Opportunistic infections have been seen, though only a few cases of TB have been seen to date.  Infusion reactions have been seen in clinical trials that are typically mild.

[ocelot556]

Maybe I'm misreading the wiki on this drug you posted, George, but among other nastiness it can cause a side effect of "Progressive multifocal leukoencephalopathy" that turns the white matter in your brain into swiss cheese?


I'll take a bent penis over not being able to talk or cognitively reason, if that's the case.

[Tim468]

When we give Rituximab to our transplant patients, we keep our fingers crossed it will make them better and not worse.

Count me out!

Tim

[George999]

When we give Rituximab to our transplant patients, we keep our fingers crossed it will make them better and not worse.

Count me out!

Tim

Good point!  

[Gregory]

Correct me if I am wrong.  Xiaflex is in Phase III trials for the treatment of Duyputren's Contracture in the US.  But it has completed the European equivalent of Phase III trials and is expected to be approved in Europe later this year and on the market there in 2010.  

Does anyone know at what point are the trials for Peyonie's in Europe and the timeframe for it's debut on the market?  It appears to me that the US is slower in its approval process and it will be several years before we can expect Xiaflex to be approved for Peyronies Disease here.  

Also, I understand that the cost of treatment with Xiaflex is more than surgical options.  As such, insurance compaines may not approve treatment with Xiaflex and certainly won't approve an off label use of it to treat Peyronies Disease.

I feel like I've just been punched in the stomach.  I had gotten my hopes up that Xiaflex would be on the  market by the end of this year.

[Hawk]

I feel like I've just been punched in the stomach.  I had gotten my hopes up that Xiaflex would be on the  market by the end of this year.

Greg,

They are having trials to see IF it passes.  While hope is good, we have to be realistic.  Data must be analyzed, and FDA decision made, marketing will begin and that is assuming the trial comes out the way we hope.

I think it is premature to think this is going to happen in the next few months,