This Is MS Multiple Sclerosis Community: Knowledge & Support

Hi Peter,

That's quite the claim that neuro made... we couldn't find anything in the NEJM on it (maybe he knows of an article coming out in the future?). That's also major news, so if you can provide anymore information on it, we'd all be much obliged.

Thanks for sharing!
-arron

Arron, One reason I posted this was hoping that someone would have a link to the article he spoke of. He said it came out a couple months ago.

I was so surprised by his statement that I interrupted his presentation ( something a shy guy like me never does) to get a clarification. "Was he talking about the patients in the phase II study?" and "are these patients now showing rapid progression?" "Yes" he said to both.

He went on to wonder aloud about how the FDA would handle the news in their licensing of the drug. This Dr. is connected with the ms center in Burlington Vt. and involved in several trials. I'm not sure where he got this news or if he just made it up.

I had planned on questioning him further after his presentation ( he was seated at our table) but the drug rep's had him cornered so we headed home.

Peter

FYI, one concern I heard from a MS specialist last week regarding Antegren is that it might be too good at sealing up the blood-brain barrier, thus preventing the immune system from getting into the brain when you'd actually want it to (e.g., to fight meningitis).

carolsue

That was a rumour started by competitors and there is nothing in the NEJM. As I remember it, a very large pharma co and its Swiss-based partner floated that balloon for seemingly obvious reasons.

The mechanism of action is unique for Antegren. The theory is that Antegren, a humanized monoclonal antibody, binds to rogue T-cells and keeps them from crossing the endothelial barrier between the brain and blood. There is nothing you can do to prevent those long-lived T-cells that are already causing damage, but those cells will eventually die. In theory, the longer a person is on the Antegren treatment, the better the results will be.

If a patient stops taking Antegren, then there is no rebound effect, but the disease will eventually resume its course.

The PII results were compelling as cited above in the thread. And the interim (12 month out of 24) PIII results were compelling enough to the FDA that they asked the developers of the drug to file for approval - something the FDA has never asked of other MS therapy providers.

As far as I know, it is not true that trials have been halted due to efficacy. As I understand it, there has been a significant effort to keep results under wraps as revealing them would jeapardize the 2 year results that should just now be completed.

Hi Meadowstream, and welcome to the site. You seem like you've done your homework on Antegren--Do you have any thoughts on carolsue's post?

Arron,

I have never heard of what CarolSue refers to before seeing it here. Could just be more fear, uncertainty and doubt that surrounds any new treatment, but I don't know. So far, Antegren has proved safer than placebo with fewer side effects (first time I have seen this.)

Take care,

MeadowStream (who is off on a business trip but will check back in a couple of days!)

I'd characterize it as uncertainty and doubt that surrounds any new treatment. The doc I was talking to didn't discount the efficacy of antegren at all, and did say it sounds like antegren is well tolerated. but he was expressing caution about possible unintended consequences, given that there are times when you'd want your immune cells to get across the barrier.

It was something I hadn't considered, nor heard about yet, so thought I'd bring it up.
carolsue

You have to look closely at the NEJM results to see the rebound effect after patients stopped taking Antegren. Its a real concern to many Neurologists, especially since Biogen is not sharing any further efficacy data. Another concern is that Antegren only works in one way. On the other hand, interferons work in many different ways. So, it will most likely be used in combination. This market is so confusing, you will hear something different depending on who you talk to. I say look at the data from the trials, not what reps tell you. Another statement in this thread was that it will be the same cost as the CRAB drugs...not true. It will be between 30-35,000 a year. Is it worth it, when it only shows a 50% reduction in relapse rate. This reduction has been seen in the high-dose inteferon trials too. I dont know, we'll see.

I think it was Pfizer/Serono that made the "rebound effect" comment - that comment can be found online in a September wire services report. Biogen and Elan responded the next day that there is no observed rebound effect (and I don't see anything in NEJM either.) Sounds like marketing palaver to scare patients into sticking with ABCR treatments.

And, as I understand it, Biogen is not refusing to release more efficacy data but must wait for PIII trials to run their full 2 year course and then they need to analyze the data before they release results. Supposedly the FDA is asking the company to keep data underwraps so that the 2 year trials will not be compromised.

As far as pricing goes the number I have heard is ~$20K annually. And is it worth it for twice the efficacy and no side effects? I say yes.

The FDA is supposed to rule on Antegren by 25 November according to PDUFA and Priority review rules (BLA was submitted on May 25 and granted Priority review by FDA.) Since the FDA asked Biogen and Elan to submit the BLA based on 1 year data, we can only assume that the PIII data is excellent.

As far as high dose beta interferon trials go, efficacy has come nowhere near that seen in the Antegren PII trails. This is not said triumphantly, but it is just a matter of fact. And the side effects of high INFb dosing are not pleasant for many (and neutralizing antibodies develop at a higher rate, too.)

Much more will be known in 5 weeks time.

Meadow,

That's interesting about what they are finding with the high dose interferon b trials. (That's the trial I was almost in. At one point, I got frustrated and actually said to my neuro that he needed to apply the "toxicology" part of his PhD to figuring out how the DOUBLE dose of the interferon b would affect people. Yes, I apologized later. LOL)

Guess I might have not been so dumb about that fact after all (i.e. that just because a "little" works pretty good, that "more" might work better! I said "WHAT???!!!") Well, now I don't feel so bad in saying that, I guess. I feel bad about hurting my neuro's feelings, but............well, you know. I figured it was common sense, ya know? Trying DOUBLE the dose of interferon when so many people have so much trouble with HALF that amount? Didn't make sense to ME, but what do I know?

It'll be interesting to see what actually becomes of THAT clinical trial study! And the results of the Antegren trials.

Deb

As an investor in Elan (the company which discovered Antegren and is partnering with Biogen on development), I am biased. However, it is scary to read about the mis-information being spouted on this board from people like "Harry Z" and "Guest". The current market for MS drugs is about $5 billion per annum and the existing players are going to do their best to spread dis-information so that you stay with your existing drug. Of course, one should not take my word for it either. My suggestion to you is not to believe anything you read about Antegren unless there is a web link to a legitimate site.

Following is a summary of Phase II Antegren results as printed in the New England Journal of Medicine showing 90% reduction in lesions and 50% reduction in relapses, with side effects that WERE NO DIFFERENT THAN PLACEBO:

http://content.nejm.org/cgi/content/abstract/348/1/15

Expected cost of Antegren is likely to be higher than Rebif ($14k per year) and most analysts are guessing between $16 thousand to $20 thousand per year. Jim Mullen, the CEO of Biogen said the following: "The highest price is currently the high-dose Rebif, which is now selling at a 25 percent to 30 percent premium for a very small increase in effect," he said. "I think the market will pay for much better efficacy. No decision on pricing has been made yet, he said."

FYI, I would not worry about cost in the sense that Biogen and Elan will not put a price on the drug which the insurance companies will refuse to pay. They are talking with the insurance companies currently and will price the drug when Antegren receives FDA approval.

http://boston.bizjournals.com/boston/st ... ily19.html

Between now and the expected approval date (given 6 month Fast Track, the FDA is supposed to respond by Nov 25th), there is going to be a lot of outsiders (of which I am one) that are willing to spend time on MS boards to provide the "truth" about Antegren. Please remember that no one in the public domain knows the Phase III results for Antegren. The end of the two-year Phase III will occur in the next few weeks. Elan and Biogen filed with the FDA for approval based on the interim one year data at the request of the FDA. However, also at the request of the FDA, the companies declined to release the one-year interim data in order to ensure that the results from the two year study are not tainted.

Biogen and Elan have said that they will release the one-year interim data for the Phase III Antegren study upon approval by the FDA. It is likely to take another six months for the company to collate, analyze, and release the two-year data.

With regards to whether Antegren will be used alone, or in combination, that is still a question. The CEO of Elan has said that it is likely to be a monotherapy but that opinion is not universally shared.

Obviously, I have a monetary interest in this, but I hope that Antegren is successful in providing an effective therapy for MS. Good luck to you all.

ElanMike,
thanks for the info and optimism. Keep in mind, however, that there is not yet any confirmation that a reduction in lesion laod and relapse rates is correlated to a reduction in progression to permanent disability. Ultimately, a therapy which slows or halts the progression of the disease (in humans) is what we need!

Good point, and since he is an investor in Elan....he has a vested interest in putting out "the good word". You sound like a rep for the company...Ive read this same info on the drug rep sites. It all sounds great, but let's face it, Biogen is great at spin- doctors know it, we know it! For example, they always talk about NAbs with Rebif/Betaseron, just deflecting the discussion away from efficacy. There is so much data to show better efficacy than Avonex, yet all they come back to is NAbs. Do they think we are stupid? I know NAbs can matter, but not for the majority of people. It will be very interesting to see how they change their tune given the high NAbs with Antegren. I just think this market is so ridiculous, and as I have said before, everyone needs to take the time to read and understand the data from a non-biased source...and sometimes, unfortunately, that's not even your physician.
On another note, I have heard that Antegren wears off after 18months (this is from a former Elan rep). In that case, I think I'll wait to see the 2 year data before trying it.

As I pointed out above, Avonex and Rebif are the same molecule - neither has the edge on the other in terms of efficacy. But, the higher dosing and more frequent dosing of Rebif is probably the cause of the NABs.

Antegren does not "wear off". The mechanism of action is as I described higher up in the thread: the MAB clings to the T cells that cause the demylinization associated with MS and keeps them from crossing the blood/brain barrier. If you stop taking Antegren, then eventually new, long-lived T cells will be generated and will cross over the BBB and the disease will begin progressing again.

Rebif and Avonex, however, have both been shown to be effective for an average of 5 years (and even then they are not tremendously effective, they only slow the disease somewhat.)

This coming month should be very exciting: Antegren should be approved and the 1 year data released (I think the 2 year trials have just finished dosing and all trial participants will now be on Antegren.)

Bebe is proving my point about people getting on these boards to spread disinformation.

Bebe pretends to have MS. But if you do a search on the ID, you will see that she has posted two other times besides yesterday’s attack on me, both times on Oct 27th. The posts demonstrate an abiding love of all things Rebif and hate of all things Avonex. That is fine -- I actually agree with her espousal of the strengths of Rebif over Avonex – but I am not an expert on the subject.

There is one thing I am sure of. And that is every MS sufferer is going to want to learn the facts about new therapies and not dismiss them out of hand like Bebe (“On another note, I have heard that Antegren wears off after 18months (this is from a former Elan rep)”).

Hence:

1) Bebe is not an MS sufferer
2) Bebe is throwing out disinformation about Antegren wearing off after 18 months. No one in the public domain knows the one year results from the Phase III Antegren trial. The two year results will not be known until middle of next year (I believe the end of the two years is sometime in November). The only thing we know is that the 1 year results were good enough that the FDA asked Elan and Biogen to file early.

Be careful. If there is no link, don’t believe it. And as far as links go, follow this one to see Bebe’s previous posts.

http://www.thisisms.com/modules.php?nam ... uthor=bebe


PS I heartily agree with billf. Slowing lesion development and reducing the number of relapses are secondary endpoints. EDSS is the important measure. We only have strong hints that Antegren is effective, no proof until the results are released. And even if effective, it is not a cure for MS. But progress is a good thing, and when the results on the 1 year are released, we will know if the fight against MS has progressed or not.