This Is MS Multiple Sclerosis Community: Knowledge & Support

Got this in an MS e-mail this morning.......More good news about Antegren.....Kim


Antegren Could Be Available in US as Early as 2005

Thought there were no new MS drugs on the horizon? Think again. In February, drug manufacturers Biogen and Elan jointly announced that they will file for FDA approval of Antegren (natalizumab) in mid-2004, a year earlier than scheduled. That means that the novel drug, if approved, could become available in the US as early as 2005.

Antegren is a humanized monoclonal antibody that is the first in a new class of drugs called selective adhesion molecule inhibitors, or SAMs. The mechanism of action is different from current ABCR drugs in that Antegren is designed to selectively inhibit immune cells from leaving the bloodstream and migrating into tissue. In MS, it is thought that the drug prevents white blood cells from entering and attacking the brain, causing lesions. Antegren is also being tested in other autoimmune disorders, including Crohn’s disease and rheumatoid arthritis.

Biogen and Elan garnered an accelerated FDA approval timeline for Antegren in MS based on the preliminary data from two Phase III clinical trials scheduled to conclude at the end of the 2004. Although the data from the first year results has not been released, industry analysts suggest that it must be strong to warrant the expedited schedule. Both trials are two-year, randomized, multi-center, placebo-controlled, double blind studies with the drug being administered by intravenous infusion once a month.

The AFFIRM (Antegren Safety and Efficacy in Relapsing-Remitting MS) trial is designed to determine whether Antegren slows the rate of relapses, while the SENTINEL trial (Safety and Efficacy of Antegren in Combination with Avonex) is investigating whether the combination of the two drugs is more effective than Avonex alone. Approximately 900 patients with relapsing-remitting multiple sclerosis (RRMS) are enrolled in the AFFIRM trial and approximately 1,200 in the SENTINEL trial.

Biogen and Elan’s announcement isn’t the only good news either. Excitement about Antegren’s potential efficacy in MS has been building since January, when a favorable six-month study from the UK was published in the New England Journal of Medicine. See our subsequent article, UK Study Finds Antegren Markedly Reduces Lesions in MS, for more details.




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UK Study Finds Antegren Markedly Reduces Lesions in MS

As previously described, the MS community is eagerly awaiting the results of the Phase III clinical trials of Antegren (natalizumab) in order to fully gauge the drug’s effectiveness. But in the interim, a small study published in the January 2nd issue of the New England Journal of Medicine has offered a vote of confidence for the drug, particularly its ability to reduce the development of new brain lesions. (1)

Researchers from the Institute of Neurology in London observed 213 patients with RRMS for six months in a randomized, double-blind trial. Patients were randomly assigned to receive an inactive placebo, 3 mg/kg of intravenous Antegren, or 6 mg/kg of intravenous Antegren every 28 days. The study’s primary endpoint was the number of new brain lesions as detected by monthly gadolinium-enhanced MRIs, although researchers also recorded the number of relapses during the study period and surveyed the patients as to their sense of well-being.

At the end of the six months, the investigators found a dramatic and statistically significant reduction in the mean number of new lesions in the two groups given Antegren (0.7 relapses per patient for 3 mg/kg, 1.1 relapses per patient for 6 mg/kg) as compared to the placebo group (9.6 relapses per patient). That means that for the groups given the active drug, approximately 65-75% of patients (depending on the dosage administered) had no new lesions develop during the study period.

The other study measurements reflected positively on Antegren as well. Patients receiving Antegren reported an improvement in well-being at the completion of the study, while those in the placebo group reported a slight worsening. The Antegren-treated patients also experienced fewer relapses than did the placebo group: 13 relapses and 14 relapses, respectively, among the two Antegren dosage groups, compared to 27 relapses in the placebo group.

Further research is needed to confirm the results of this trial as well as demonstrate continued benefit and safety during long-term use of the drug. But should the Phase III clinical trials return similar results in a larger number of patients over a longer period of time, Antegren could potentially prove more effective than any immunomodulator drug currently on the market.

(1) Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003 Jan 2; 348(1); 15-23.

Hi all

I went to an MS Active Support (Biogen) sponsored event today. Presenting neurologist stated he thought Antigen would be available by January 2005, maybe later, but the practice he is with is already remodeling their offices to be able to give the IVs there rather than cancer treatment IV suites.

Once monthly IV treatment to take 2-3 hours was his "take" on it.

Sharon

OK. Was just trying to see if I could post. I am an academic clinical research physician. I think I have MS, although all my tests were negative and the expert I saw didn't think so. But he didn't know what I have. It's a long story, but I presented with numb hands (not carpal or ulnar tunnel syndromes) that anatomically had to originate in the cervical spine, got worse with heat, and got better with steroids. I have other funny "little" symptoms too, but writing about them will only increase my anxiety.


Anyway, I am very familiar with clinical trials, since I run them. But not in neurology. The good news is that the fact that the company is filing for approval for Antegren after one year, rather than the planned two years, is good. However, the bad news is that these trials have ethical review boards and if Antregen was really, really great, they would have had to close the control arm of the study at one year, since it would be unethical to continue it. Also, the fact that they need about 1000 patients to see a difference is not so great. With really great drugs, you can see differences in smaller groups of patients.

So, I'm guessing, but it seems that Antegren is a good drug, but not a miracle cure.

worried: interesting point, but remember that in one of the trials, Antegren is being compared against Avonex, so the placebo group is still getting a widely-accepted therapy for MS (they're not just being left to decline unabated while the active group gets treated). I think that does something to address the ethical issue, but certainly your point is well taken.

As for your point about the size of the trial, I'm left very confused. When small trials are conducted, everyone complains that it can't be considered statistically significant (a common phrase we see in the research studies we post is, "the results need to be repeated in a larger trial setting to verify validity"). More people exposed to the drug surfaces more side effects and levels the playing field in terms of extreme individual responses (>=2 standard deviations from the mean) swaying the conclusion. With your experience in the field, it would be very beneficial to the rest of us if you could address my thoughts and show me the flaw in my thinking.

Finally, I think everyone's expectations for Antegren should be that it is
a) more convenient
b) less minor side effects (since the # of injections goes down)
c) possibly greater serious side effects (method of action is new)
d) better control of inflammations (which is not the whole story in MS)

Basically, we would cautiously view it as a positive step in the evolution in MS drugs, but definitely not a cure.

Thanks again for posting, please set up an account and join us regularly-- we could definitely use your expertise in evaluating many of the things discussed on this site!

I'm a first time poster to this or any other MS related forum.

I'm writting on behalf of my younger 26 year old sister, diagnosted with having MS.


Here's her experience with Antegren.

Being a seemingly healthy person, with no prior medical conditions, she was diagnosed with MS in 2001. She was approached by her neurologist to participate in a Natalizumab study, (Biogen Protocol Number C-1801) at St. Micheal's Hospital, in Toronto, Ontario. She was on the drug for over one year. One night, several months ago, she experienced what she thought was a relapse of MS. She called the doctor & hospital with hours of experience MS-like symptoms. They told her not to worry for at least 24 hours. That night she suffered a debilitating stroke.

After seeing the neuroligist, they opened her study files and confirmed that she was in fact part of the study group being receiving Natalizumab.

She was assured by the neurologist (who is the primary investigator for study) that this was not a result of the drug. However, she was immediately removed from the study. None of the doctors, specialists that were called in to investigate her case could provide an explaination as to why a 26 woman, with no blood, heart problems suffered this stroke.

Still want to try Antegren?

ELMO- Im so sorry to hear about your sister. This is the first real case I have heard about....as I have heard rumors of stroke occurring in more than one patient in this trial (3 patients).

Your stories need to be confirmed. Elmo, please provide your contact information to Arron. If either Arron or myself can confirm the particulars with your sister's neuro, I would be more than happy to broadcast your story to the wider investment community.

If you are not willing to confirm your story, then we have to go back to my theory that there are people willing to spread dis-information on Antegren in order to protect their economic interest.

If you don't trust me, trust Arron. Ball is in your court.

Bingo. We are all about disseminating information, but have to be vigilant for the risk of inadvertently legitimizing disinformation.

That being said, it is quite possible that the stroke was indeed spurred by the therapy, given that all therapies can be poisonous to any given individual with a particular genetic makeup, drug sensitivities, etc. Even "safe" things like Aspirin can cause serious damage in some small percentage of people(for a ridiculous example, if one happened to eat a million pickles, I guarantee they will die). What's critical to know is if the therapy raises the general risk for the average person-- e.g., does Antegren raise the risk for a debilitating stroke in EVERY individual who takes it (or even a large subset), or is it a very isolated condition which could have as much to do with the IV administration as the drug itself.

Very important questions, with critical implications. Elmo, please accept our thanks for your sharing, and understand our desire for more information.

Thanks everybody,

I understand and appreciate your responsibility in validating my sisters story. Please understand I am not trying to spread any disinformation, I am simply telling you what happened to her, and trying to get answers for ourselves.

We are trying to find out if this has happened before and if this information has been documented in the study results.

Thanks for your help and understanding. Any information is much appreciated.

As "Guest" implied, has anyone else heard of other study patients experiencing strokes?

ELMO

Elmo,

I take your note as confirmation that you are unwilling to have anyone confirm the facts behind your story.

What is interesting is that you posted your story on this thread as “Elmo” on Tuesday, Nov 2 at 10:24 a.m. An entry characterized as “Guest” replied to your story two hours later and spread a rumor that three more people had strokes while taking Antegren. Elmo referenced the reply of “Guest” in his subsequent message, indicating that Elmo and Guest are not the same individual.

The exact same story told by Elmo (sister suffered stroke taking Antegren) was posted on another thread on this website on Tuesday, Nov 2 at 10:18 a.m. However, it was not posted under the Elmo name, but instead was posted under “Guest”. Follow this link to confirm:

http://www.thisisms.com/modules.php?nam ... =3847#3847

So Elmo, please explain the same posting under two different screen names which were six minutes apart. Alternatively, allow Arron or myself to confirm the facts of your story by providing contact information for your sister’s neurologist.

[edited by moderator]

PS As highlighted in the New England Journal of Medicine, the Phase II results for antegren did not show any side-effects that were different from placebo. Results for the Phase III study have not been released. It is my theory that message boards will be vulnerable to malicious rumors from antegren competitors until the Phase III results are released

PPS As I noted earlier, I am an investor in Elan, the drug company that developed antegren with Biogen, so I have a natural bias.

ElanMike, the posting by Elmo with his name as guest in one post and as Elmo in another is just a simple login in situation, It happens every now and then and is not a mystery or uncommon, Arron or myself can verify every ip from those who post here ..


And if you read the posting , he is asking for help and validation, he simply stated what happened to his sister and is asking for help in trying to understand what happened, perhaps he will be able to provide more info and then the situation can be researched..

Multiple variations can cause a stroke to happen, It could be many different reasons, his logic in his sadness over his sisters unfortunate situation is simply something new came into play, she was fine before this was interjected into the situation and his only logical thought is to first look at what has been interjected, but the fact is her stroke could have been caused by many different reasons..

As for the post by someone else under the name "guest" stating the heard a "rumor" that more strokes were caused by this treatment, the mere term "rumor" is self explanatory, It does no imply validity, It merely gives some un-verified information that should be researched for validity.

Perhaps you could spend some time providing your research into every aspect of this, please provide links to all your research references showing all misinformation concerning stated problems with Antegren, and the facts showing that the misinformation is such, as an investor you must have done extensive research into all aspects of your investment, and any smart investor not only looks for the parts that show positive specifics as per making an investment in anything, they are just as diligent in verifying every fact for validity ..

That is how the reality of the substance in discussion and investment are verified..

We look forward to your research and verification and links.

Thank you, Philip

<Arron or myself can verify every ip from those who post here .. >

I would appreciate if you would compare the ip for Elmo with "Guest" who replied to Elmo's email at Tue Nov 02, 2004 12:49 pm. This would at least settle the question that I have raised.

Although I have doubts about the veracity of Elmo and Guest's statements, there seems to be little point in pursuing further beyond my request above. As you suggest, I will look to provide a summary of known facts on Antegren based on links to reliable sources.

Clearly, until approval is granted by the FDA and the Phase III data is released, the MS boards are going to be vulnerable to rumors and innuendo.

Different people, in different places...

I must say am very taken aback at the responses I have received.

Yes, I did post multiple messages on different threads. As I stated, I am first timer to this/any forum, and posted in several places as I was not sure where I should direct my question.

I initially posted message as a guest, and then got a personal login, as instructed by Aaron.

I am totally willing to share the results, I have scanned and am ready to send doctors notes, test results and all other data I have in my possession. I was instructed to pm Aaron, with the notion that he would be the most appropriate person to send the info to. I never received a pm back.

If you want to do a ip check to verify, the other story about "rumors of three other people having a stroke" please do. I assure you it was not me. However, I am very much interested in talking to the person who did post it.

I see this is a very closed-minded discussion group, who does not want to hear anything bad about this drug.

ELMO

Elmo,

I apologize. Please follow-up with Aaron.

The release of the one-year data on Antegren makes no mention of stroke as an adverse event. Therefore, assuming your story is true, senior management of Elan and Biogen have made false statements to the marketplace about the safety of Antegren in my view.

Besides contacting Aaron, I would also call any newspaper reporter that you know. This is as big a story as Vioxx.

As you might guess, until your story is confirmed, most people are going to believe the companies did not violate federal securities laws. But that should just provide you with impetus to get your story confirmed and circulated to the MS community.

Again, apologies for the tone of my previous responses.