Efficiency of Antegren

[OddDuck]

Yea, and still no mention of contraindications (i.e. blocking VLA-4).

Deb

EDIT: The article says:

Natalizumab, a humanized monoclonal antibody, is the first alpha-4 integrin antagonist in the new selective adhesion molecule (SAM) inhibitor class.

It may be the first alpha-4 integrin, but it's not the first "integrin antagonist" or selective adhesion molecule inhibitor ever put on the market. Thalidomide was (and is now back on the market again with the following contraindications that come with it: http://www.fda.gov/cder/foi/label/1998/20785lbl.pdf )

I rest my case.

[MeadowStream]

Well, the 1 year PIII data is out and it is pretty amazing. 66% reduction in relapses v 50% in shorter, smaller PII trial - in line with theory that longer use leads to increasingly better results. EDSS results will hopefully be forthcoming after approval.

There was no concern over safety voiced today by the companies either in its press releases or in their conference call. There was no mention of stroke-related adverse events. Only 5% had any side effects and most of those were only experienced during first injections.

This should be great news for MS sufferers everywhere. Congratulations.

MeadowStream

[billf]

MeadowStream/OddDuck,
to say that Antegren is an anti-inflammatory because it prevents inflammatory molecules from crossing the BBB is a stretch - true anti-inflammatory agents work in a very different way, but I'll grant that we are just arguing semantics.
However, to say that Antegren works by preventing inflammatory molecules from crossing the BBB is worth contesting as I believe that this is only speculation. As you know there is some recent research showing that the inflammatory response may NOT be something we want to suppress - that it may in fact be beneficial. Definitely, Antegren works by filtering the BBB traffic, but do we really know that it is the blocking of inflammatory molecules that gives the beneficial effect? Until that is proven, I think it is misleading to call Antegren an anti-inflammatory agent. This all may seem too nit-picky, but I think we should all be very careful in discussing the science of MS.

[OddDuck]

Bill,

I totally agree. It appears, though, that the pharma itself sort of tends to refer to Antegren as an "anti-inflammatory". And sometimes trying to explain it in layman's terms can be a little difficult. I tried by saying previously:

Will it stop inflammation DIRECTLY? No. It stops the migration of the cells through the BBB to the CNS and brain where the inflammation would (or might) cause damage.

Notice where I said "might". And that it does not stop inflammation directly (i.e. thereby not making it an anti-inflammatory). Sometimes I think I talk backwards. I probably should have said "...where it is THOUGHT by some researchers that inflammation would (or might) cause damage".

And I also totally agree with your other statements you've just made. And as I posted before, if that IS the case, i.e. that you might not necessarily want to prohibit ALL of the inflammatory response, etc., then you might be doing more harm than good. I mentioned somewhere the high risk of infection running rampant should you contract something while on Antegren.

And besides, Antegren doesn't even block the APC cells from infiltrating the BBB, anyway. What happens then?

You know what I'm "thinking". If I were someone considering taking Antegren, I'd make darn SURE that test results showed that part of my physical condition degeneration was due to inflammation....pure and simple. And that's just the first factor in the whole risk assessment equation. As you said, then I'd have to consider how I felt about the theories surrounding how much of the T cells I want to mess with, etc. etc. If test results showed I was not experiencing that much "inflammation" in the first place, I'm sorry, I'd speculate that Antegren would not be the best thing to take in any event!

I still say there's just not enough overall research on this. And shoot, like I said, when I started looking into it, I didn't expect to find anything that would cause me this much "hesitation", shall we say!

Deb

[MeadowStream]

OD,

You said "If I were someone considering taking Antegren, I'd make darn SURE that test results showed that part of my physical condition degeneration was due to inflammation....pure and simple."

I am not sure I understand what you are saying because the data released so far shows twice the efficacy with respect to relapses of any other treatment (and we are still waiting on MRI and EDSS data.) How could you ever know that your degeneration was due to any one factor exactly? Why wouldn't you choose the best and safest therapy available? Why are you more skeptical of Antegren than alternative therapies (Antegren has 5 years of safety data without - as I understand it - serious adverse events.)

MS[/i]

[OddDuck]

Meadow,

Well...........I've posted in several different lengthy threads everything that I've found that personally makes me hesitate about Antegren. (Enough for me to express my concerns in writing to the FDA). I won't bore you with it all again right here. You'll find the one thread here entitled "Biogen Idec" and the other one under General Discussions entitled "VLA-4 Antagonists (i.e. Antegren)".

Five years of data? And published by whom? Biogen? You will see in my other threads some of Biogen's own research published about VLA-4 antagonists (with it not being so "flattering").

Hey, remember, though. This is just what I surmised from all the data I located. I'm sorry.......I just don't completely trust clinical trial data done and submitted by interested pharmas. And as I mentioned before, even the FDA has found that they can't trust it completely either, so I guess I'm not alone.

Test results can show what is happening and/or may be causing damage in MS. At least it can indicate whether it's inflammation or not.

Antegren doesn't even do a THING for anything else. It ONLY has ONE mechanism of action. It ONLY blocks VLA-4 (well, correction, alpha 4 beta 1, which is VLA-4, and alpha 4 beta 7), which in turn disallows T cells to cross the BBB. It doesn't stop anything else from crossing. JUST T cells. And the only thing T cells are mainly associated with in MS is inflammation. That's it. Antegren only does one thing. So, if you don't have inflammation in your body and you STILL have damage that is being caused by MS, then you know that blocking the T cells from crossing the BBB won't help at all, and might even hurt. Not to mention what will totally blocking VLA-4 do (i.e. side effects as I am questioning in my other threads).

See....that's another thing I get frustrated about. How many doctors must NOT be utilizing the adequate tests and/or don't know how to interpret the tests accurately enough, or the question that you just asked wouldn't be asked. Frustrates the heck out of me about some physicians. (Note I say "some", not "all".)



Deb

EDIT: Sorry, I keep finding typos that I'm correcting.

[bebe]

Antegren doesn't even do a THING for anything else. It ONLY has ONE mechanism of action. It ONLY blocks VLA-4 (well, correction, alpha 4 beta 1, which is VLA-4, and alpha 4 beta 7), which in turn disallows T cells to cross the BBB. It doesn't stop anything else from crossing. JUST T cells. And the only thing T cells are mainly associated with in MS is inflammation. That's it. Antegren only does one thing. [quote]


Very good point. Its interesting b/c there are so many biological pathways at work in MS, would acting at one site (ie. the BBB) solve the problem? It makes sense that Natalizumab would be most beneficial as a combination therapy, with an interferon. Interferons work in the periphery, at the BBB, and possibly in the CNS...in other words at multiple sites.

[OddDuck]

Bebe,

Thanks (for telling me I make sense, at least....sometimes I wonder. )

That's my thought. Antegren might likely be more beneficial as a combination drug and/or used as an "acute" treatment, similar to how the steroids are used.

Deb

[MeadowStream]

OD,

I guess what you are saying is that you are just very, very cynical. And maybe with good reason - only 50 years of time will tell. But, again, the data is objective and relapse rates and MRI scores and EDSS scores tell the story. You are right that trials are sponsored by Biogen, but the trials are run according to FDA-approved protocols, data is available to investigators, and the discerning eye can see when something is being brushed under the rug (we have all seen Rebif and Copaxone data spun in interesting ways, and Biogen surely would like to see Avonex continue as a first line therapy.)

Antegren is the best treatment on the market for MS. As to whether a combo treatment is advisable or superior to monotherapy, the results of the SENTINEL trial will be available in a few months. I suspect that monotherapy will be the therapy of choice, however.

I can't imagine an MS patient with active MS not choosing Antegren as his/her treatment, not only because of the vastly superior efficacy relative to ABCR, but also the incredible safety profile to date (PIII showed only 2% more adverse events in drug arm as in placebo arm.)

You can always wait for more data, but I hope that, if EDSS and MRI data confirm the relapse data, patients take advantage of Antegren.

MS

[OddDuck]

I'm only "cynical" about Antegren. And that's based on extensive research that I did. And I didn't start OUT being cynical of anything. (And might I also respectfully add that "name calling" or a feeble attempt at a personal attack doesn't appear to me to improve or flatter your position any.)

Remember, I work in law, the political world, and have worked on the "inside" of the medical industry. I've seen it all. The dirty underside, if you will.

So.....if I'm considered cynical (I call it duly and reasonably cautious, especially once I've done extensive research and read information from more avenues than just one), then so be it.

As I've said before. People can make their own choices and believe and read only ONE side of things if they wish. I won't even call them any names nor attempt to attack them personally for it.

I'll just leave you with one word, though............Vioxx. Ok....let's make it two words..........Vioxx and Thalidomide. (I'm certain there are many others, but I believe the FDA can fill you in on what those other ones are.)

All the best to you!

Deb

[MeadowStream]

Deb,

I was not name-calling or being disrespectful in any way. I do not consider cynicism to be a bad thing in many areas.

But, comparing Antegren to the most recent big drug with issues does move my own cynicism meter needle a bit. How much research could you have done about Antegren?: there just isn't much public data other than the PIII top line data and more comprehensive PII data - and it was all great data. Why pan something by giving non-related personal background information instead of specific Antegren-related information?

Again, we now have a fair amount of data that supports the claim that Antegren is not only far and away the best treatment for MS yet developed, but also data that supports the notion that the longer a patient is infused the better the results.

I respect your choice to avoid the best treatment based on your own skepticism of drug companies and the process as you have experienced it. But, then perhaps you should view all treatments through the same lens.

MS

[OddDuck]

????

Did you see all the research I have done regarding VLA-4 antagonists? And posted? Well, ok....I didn't post it "all", because it would be mounds of it. I researched in depth both the company AND the chemical.

Antegren is simply a VLA-4 antagonist. Do some research on VLA-4 antagonists yourself (or read the thread where I did a lot of it). Also, do some additional research from there on about what happens to fertility, miscarriage and birth defects when VLA-4 is blocked. Do some in depth research into integrins and their complex physiological functions in the body. THEN talk to me.



All I'm posing are some valid "questions". It seems pretty "odd" that nobody can present alternative evidence that my "caution" is misplaced.

Note........I say "caution". I'm a researcher by trade. Believe me, my research has to be pretty sound or I'd have my butt in a sling many times over the years. My research, data, and hypotheses are depended upon in courts of law.

Besides, I never said Antegren wouldn't be helpful, I am just asking if the side-effects have been FULLY investigated, and if so............show me.

And as I said....I haven't come to any conclusions, just posed some questions that nobody seems to be able to answer, can they?

Deb

EDIT: Also, a very prominent neurologist even requested that I do some pharmacological research for him on a couple of different things. Do you really believe that if he didn't think he could rely on my correlations, etc. that he would ever have asked me to do it for him in the first place? Sorry........sounds like I'm bragging, but that's not it. I'm just explaining that my credibility is pretty high and trusted. There is no way I'd ever jeopardize my hard earned reputation in research by being "sloppy".

SECOND EDIT: Meadow, the more I think of it, the more it sounds like you haven't read most of my posts over the last few months to get a "feel" for who I am, what I do, etc. The chemical/scientific research I did is under "General Discussion", not this category.

THIRD EDIT: Oh..... ....and believe me, I DO put EVERYTHING through the same "lens" before I make comments. I rarely leave too many stones unturned.

[MeadowStream]

I did read some but maybe not all of your posts. I understand your concerns, but so far, at least with respect ot Antegren, they have not manifested themselves. I think where MS is such a debilitating and ultimately life-threatening disease, your concerns are less important that for a less severe indication.

I think that if Antegren prescriptions were being written for headaches, then I would be more concerned about it than say, Tylenol. So far, Antegren is shown to be very safe relative to other treatments and far more effective.

How do Biogen and Elan respond to your concerns?

MS

[OddDuck]

I'm letting the FDA ask them.

Deb

[OddDuck]

But then again, there are so many people posting to this Board who don't/won't identify themselves, so who is to know really WHAT their response is/might be.

Also, based on past performances of pharmas in general, I would surmise that it would be very similar to Merck's response over the last few years (at least until disaster struck)...........which is.......... "no comment".

Deb