Antegren: New Treatment for Multiple Sclerosis: Explained

Medicine & Biotech Forum

PROMISING RESULTS ANNOUNCED FROM CLINICAL TRIAL

Summary: Promising results from an early-phase clinical trial in MS of a monoclonal antibody were announced at the 17th Congress of the European Committee on Treatment and Research in MS, in Dublin on September 15, 2001.

The antibody natalizumab (Antegren®; Biogen Inc., Cambridge MA and Elan Corporation, PLC, Dublin), given by monthly intravenous infusions, functions by blocking the adhesion of immune cells to blood vessels and can inhibit movement of immune cells from the blood into the brain.
A six-month, early phase clinical trial involving 213 individuals with relapsing-remitting or secondary-progressive MS was conducted at 26 clinical centers in the United States, United Kingdom and Canada.
Those treated with Antegren had fewer new enhancing lesions detected by MRI than those treated with placebo, and treated patients had fewer relapses during six months of treatment. No benefit on progression of disability was detected in this short study.
The sponsors have stated that larger-scale clinical trials of Antegren, alone and in combination with Avonex® (interferon beta-1a), are planned.


Details: Promising results from an early-phase clinical trial of a monoclonal antibody that blocks movement of immune cells into the brain were announced at the 17th Congress of the European Committee on Treatment and Research in MS, in Dublin on September 15, 2001. David H. Miller, M.D. (Institute of Neurology, Queen Square, London) reported that the antibody natalizumab (Antegren®; Biogen Inc., Cambridge MA and Elan Corporation, PLC, Dublin) caused a reduction in accumulation of new enhancing lesions detected by magnetic resonance imaging (MRI) and a reduction in relapses of MS.



Background: Antegren is a molecule designed to interfere with movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier,” and into the brain and spinal cord. This monoclonal antibody attaches to a protein (called alpha 4-integrin) on the surface of white blood cells, which serves to block such immune cell movement. Antegren was discovered by Elan and is being co-developed by Elan and Biogen.



Study: Two hundred and thirteen individuals with relapsing-remitting or secondary-progressive MS were studied at 26 clinical centers in the United States, United Kingdom and Canada. Individuals were given one of two doses of Antegren (3 or 6 mg per kilogram of body weight) or placebo treatment, delivered by infusion into the vein (intravenous) once every four weeks, for six months. The primary goal of the study was to evaluate safety and to determine the impact of treatment on accumulation of new enhancing lesions detected by MRI; secondary goals included impact on MS relapses and progression of disability. The trial was double-blinded, meaning that neither the physicians nor the study participants knew who was on placebo and who was on experimental treatment.



The six-month study showed a reduction in accumulation of new lesions detected by gadolinium-enhanced MRI. An average of 9.6 new lesions were seen in the placebo group, and 0.6 and 1.2 new lesions seen in the low- and high-dose Antegren groups, respectively. Placebo-treated patients experienced 34 relapses during the six-month treatment period, compared with 19 and 14 relapses in the low- and high-dose Antegren groups. No changes in measures of disability were detected in any of the groups during the study.



Antegren was relatively well tolerated. The most common side effects included headache, weakness, and urinary tract infection. Those treated with Antegren also showed more gastroenteritis, rash, urinary urgency, back pain and fever, and infrequent allergic-type reactions.


Conclusion: This clinical trial showed promising results, but a longer trial involving greater numbers of individuals monitored clinically and with MRI will be required to determine whether Antegren, alone or in combination, might have a role in the treatment of MS. The sponsors have stated that larger trials are in the planning stages. Because Antegren functions by inhibiting movement of immune cells into tissues where they can do damage, it may have potential for use in MS and other inflammatory diseases.

--Research Programs Department

From: National Multiple Sclerosis Society

Considering the severity of MS, these "potential" symptoms could very well be considered the "lesser evil".

well, not to make light of the matter, but that sounds like something someone who's never had a urinary tract infection would say..

To be honest, I really don't know what all's involved with MS and its severity.. so I guess I'll read up a bit here..

Sure.

Knowing somewhat of what MS can do to someone, if you held up and presented to someone urinary tract infection in one hand and MS in the other - (and they had to choose) I'd think more people would take even the prospect of passing a kidney stone over the debilitating state that MS can provide one's existence.

Stephen Hawking has ALS (something something sclerosis). I can't say how much one is related to another - but that might put it in perspective. Of course, if you have no desire to do anything terribly physical for the rest of your life - it may not be so bad. He seems to be doing a pretty good job.

Well I love a debate. I wonder what Meds you guys are on? Ive been on Avonex, Rebif (alergic) and now Betaseron. I've had MS since 1985. I was diagnosed twice. The diagnosis I knew about was in 2001. When I went to visit the neuro I found my military medical records and there were entries about MS from 1985 to 1987. None the less I was selected to participate in the clinical trials for Antegrin but ended up not on Avonex and into a relapse.

Whats my point. Well I am tired of doing the shots. Didnt like Avonex (needle phobia), had a reaction to Rebif, and Betaseron is tolerable... I had cold and flu like symptoms with Avonex, I dont with Betaseron....but I suppose if I want to live a normal life this is the way its to be. If Antegrin once a month gives me a headache for a day or so I will be happy since the results look promissing for this treatment. As with any of the therapies...ABCRs I could without a second thought not do my shot a night or two...which I have done. Doubtful that I would neglect going to get my once a month IV. There are no guarentees BUT I will be switching as soon as this product becomes available. Guarenteed.

I myself am counting the days until this drug is available. I can take and welcome the side effects if there is a chance that my MS progression will be slowed or even stopped. Until you or someone you know has to deal with it you will never understand what it is like to have MS.

Hi! My mom has had MS since 1980. She's 67 now and lives in Romania. Doctors over there told her that Avonex, Copaxone, Betaseron, etc. are useless for her stage of this terrible disease. Therefore, when I heard about Antegren, I started to hope again for her. Does anybody have any idea when this medicine is available and how much il will cost? Thank you in advance!

"Compassionate release" (no idea what that means) is set for late 2004. Full release is set for 2005. No idea on specific dates or prices. This is in the USA based on FDA guidelines for approval. All can be subject to change or revoked if something happens in trials.

Dear Sean Kelly. You have the same name as my son so I'll cut you some slack.

I've been living with MS for about 16 years. I've only known about it for about 4.5 years. Let me tell you, comared to what I deal with, I'll take a urinary tract infection once in awhile. And if you know what the potential side affects are, you can do what is possible to reduce the risk of side affects. Like drink a ton of cranberry juice to help that urinary tract keep infection away!

MS is beyond pain. For example, I deal with fatigue (not just tired, but beyond totally exhausted), insomnia (there's a cruel joke, fatigue and insomnia), cognitive impairment such as recall (the inability to recall something from memory when you want to) and something else coming out of my mouth when I intend to say something (seeing another person in my line of site may cause me to say that name instead of another person I may be introducing). I have balance issues so I fall or walk into things alot (recently sprained my ankle so bad that it would have been a better time healing had I broke it). I have speech trouble at times and sound either drunk or like an idiot (combine with balance issues and try to convince someone that you weren't drinking). And I'm lucky compared to most. When my cousin is affected, he has trouble walking and using his hands. All of my symptoms are invisible so I don't appear to have anything wrong with me. Makes for a very frustrating life when others think of you as "healthy". Combine that with what I beleive in my mind, that I am healthy and I believe I have the ability I did before I had to deal with all of my symptoms. But, no matter what, every day I'm reminded that I don't have the energy my mind believes I do. I've had to alter my career as I was a computer professional. With cognitive impairment it was ludicrous to think that I could keep learning new technology and be able to speak to a client about it. Now I manage consultants, kind of funny when I have to remember all the names of my 120 some employees or what they do. I'm a single mother and it breaks my heart that I can't do some of the things I enjoy with my kids. Like parties. I have noise tolerance issues and a bunch of kids in one place at the same time will cause me major frustration and difficulty as well as provoke the mood swings I have. All of which adds to the depression that so easily affects most of us with MS.

Now, all that being said. I'm a pretty happy person. I try to make the most of what I have and not let all of the above drag me down. I find out what works and I do it. I realize that I can't do it all, so I don't and I'd much rather go outside and rollerblade with my kids or hit some whiffle balls with them than vacuum or do the dishes. They will sit for a little bit longer. You rarely see me without a smile on my face and I have a great sense of humor. And as grand as life is, I'm given so much to make fun of within what I deal with having MS. Most who know me really well can joke with me.

Most of us with MS know all about side affects. Everyone with MS is different and we all take a variety of medications. Sometimes it's hard to know the difference between what is a side affect, what is a symptom and what is just something else. Sometimes we don't care, it is so much easier than without our meds.

This drug - Antegren - is such a tremendous breakthrough for those of us with MS. It is only half the battle though. This will halt the progression but we will probably still face symptoms from the damage that is already done. We all still need to do what we can to promote the research into repairing the damage. Much of this will come from stem cell research. Since government funding is limited here, the funds will come from corporate and private donations. Do what you can, please, everyone...

I happened to stumble across this while searching out information on the initial Antegren study with MS. I am currently participating in the current phase of Antegren/placebo with Avonex.

When I was initially diagnosed with MS there were no treatments readily available. The symptoms were treated without any hope of treating the disease. Since that time there are now a number of MS drugs available, but the efficacy of all of them is marginal.

Many of the potential side effects highlighted in the article are things that many of us with MS deal with on a freqent basis, with or without medications.

The promise of a potential new treatment for MS and one that in the initial clinical trials proved itself through reductions in the EDSS (disability index) of many patients and in the reduction of relapses, etc.

Antegren shows promise and I am thrilled that the drug makers are working on something that will help individuals with MS continue to lead productive lives.

Hello,

We have heard last fryday 12-9-03 that my daughter Martine has MS. She is 21 years old. Now we are looking for information about medicine etc. I have read about Antegren and I hope this medicine will work without to many side effects.
It is a pitty that this medicine is for sale in late 2004 or 2005. I have red your story's and it gives me hope for this new treatment. Thank you

Duub my heart goes out to your daughter and to you. Not only am i anxiously awaiting antegrens approval, my dr. seems excited about it too. Making me even more optimistic about it.

Duub ... As a newly diagnosed "family", I would highly recommend getting in touch with the local MS Chapter. I'm not sure where you are in Indiana, but the state chapter can be found at http://www.msindiana.org/

In addition, I would definitely talk with the doctor about which medication may be suitable for your daughter at this time. There a number of treatments available now which help to slow the progression of the disease - and, until a cure is found, this is one's best recourse in continuing to live a normal life.

My best wishes go out to you, your daughter and the entire family which is affected by the diagnosis. As an individual with MS, I don't want to downplay the consequences, but many of us continue to live pretty normal lives. I hope you will be able to find some answers that will help you to cope.

I will mention to my neurologist about Antegren and see what he says. I've been asked if the Avonex works. How do we know? Do we skip taking the shot for months and then know the answer or do we assume since we are on the shot it is working. I am interested in Antegren since I do have MS and recently diagnosed with Ischemic Colitis. Recent article on Antegren states it is helpful for patients with MS and autoimmune disorders. I personally am ready for one pill that does wonders but ...... we can all dream.

when will this drug be available. I am secondary progressive and slowly going down hill.

The article that was in our Sunday paper mentioned that the Antegren would not be available, if on time, until 2005. Long time to wait but I am sure they want to make sure all the lab rats complete the race......

A wife of a gentleman from work is on chemotherapy because her MS is so progressive. Very severe treatment but whatever works..... as long as it works, right?

In the grand scheme of things, 2005 is not such a long time to wait. As I stated in my earlier post, when I was initially diagnosed with MS there were no drugs available to treat the disease - only symptoms. The "chemo" drug being used is Mitoxantrone (Novantron) which has been approved for secondary progressive MS. Two studies suggested that it may be of some help in reducing progression and relapse rates. Cumulative doses can have toxic effects on the heart, however, and so the drug is only used for a limited period.

A promising breakthrough with Antegren is that it may slow the progession of the disease - dramatically - and perhaps give individuals a chance to eliminate the chronic progressive phase of the illness. Only time will tell, but it could turn out to be a great boost in MS treatments!

I want to send my best wishes to your wife's colleague, primary (or secondary) progressive MS is a tough battle to fight.

I, too, will be glad to see a new treatment for MS. I thank my lucky stars daily that my MS has been mainly just a disease in name only. Yes, I have symptoms but no different than someone at work who has a headache today or a bad back yesterday. Only difference is I will have MS tomorrow and next week. Having MS sucks but having "slow boat to China" MS is nice compared to others who have the aggressive MS. For them I hope there is a cure sooner than later.

Yes I too am thrilled there is hope, my ms has turned progressive and it is tough, i am in a wheel chair most of the time, hard to believe five years ago i was playing tennis and racquet ball and challenging my boys in weigh lifting. Doing the treadmill with my hubby and swimming daily for 35 minutes. Went to bed one night woke up the next with my right side asleep. When i went on Avonex i got part of my life back. But they think I developed antibodies and have changed to secondary progressive. so changed to copaxone, now added IVIG and methotrexate.I am weak. so anything new brings hope. But I still teach high school and keep my eyes on the Lord.

I have had MS for 20 yrs & diagnosed in 1990. I too was diagnosed before the new drugs were released. I have spent this time treating the symptoms & trying just to maintain a healthy lifestyle & attitude. Attitude is so important & hard to maintain when dealing with MS, therefore, I find antidepressants to be very important for this. I work out at the gym 3 times a week with Nautilus equipment & the strong muscles help in so many ways...when I fall I can catch myself. I use a cane & a wheelchair for long distance mobility. I recently had an MRI which gave me a big reality check. Many lesions so my Neurologist strongly recommended Avonex. Even though I was under the assumption that these drugs were not helpful at this stage, she disagreed & felt that the sooner you can get on them the better & to slow progression until Antegren came on board to stop it.

My answer to the question of why anyone would trade MS for Antegren side effects seems so obvious to me. MS is progressive & without stopping that you will eventually be faced with things equal and then worse than the side effects mentioned! Ultimately we do want to reverse it, of course, but I'll take stopping it for now.

While taking a much needed chill this morning, I happened on CNBC and the Biogen/Elan news. quickly called my husband and told him I might have a great investment for us. ... How cool if Antegren could help my MS and portfolio!.
My story runs along the same lines as most who participate in this forum. Tis the $#!% that happens. How great for ours and future generations that autoimmune and neurological disorders are warranting attention/funding.
I'm hopeful.
Bravo to the mom (with a dirty house!), former info techie, teacher. I'm all of the those things too. MS just happens to peek it's ugly head in the door occasionally.

I wonder if there's any research being done on the front of "gene therapy" as pertains to MS. If successful, as promising as Antegren seems today, a gene therapy treatment for MS might make Antegren look like a joke.

My husband has secondary progressive ms and is on betaseron and has been the whole time. He swears that had it not been for beta he would be dead by now. He's had ms since 1994 and is wheelchairbound but optimistic. All we have been praying for is to first stop the progression and then worry about a cure. I am hoping that the antegren will accomplish that.
I just wanted to tell everyone to keep the faith and realize if there was ever a time to have ms now is the time because the last decade has had the most advancements in MS research and medications being offered. Something even better is right around the corner!!!!

Ok, must really go get the children but couldn't miss a chance to chat.
Agree that Antegren (still 2 years away from reality says my sources) might offer hope for somewhat of a stall.
THE REAL EXCITING NEWS IS ON THE NMSS WEBSITE. BIG MONEY (5MIL) Funding OFFERED FOR 'REPAIR' WORK. Imagine some homegrown myelin on the horizon.
Check it out. www.nmss.org

PS. Mr. Kelly. always wondered if that precious water pipe might be what got me into this pickle in the first place. ....naaah.

I just spotted an article: www.elan.com/News/full.asp?ID=578660
that state that an application was recently submitted to the European Medicines Agency for approval of Antegren. This is encouraging. My daughter, age 21, was recently diagnosed with MS. At her neurologist follow up appointment today, her doctor told us that hopefully next year, this drug would be available for her. She's currently on Rebif; the doctor said she'd switch her over to Antegren because she felt she'd be an excellent candidate for it. Looking at the limited information on how this med works, it appears as if it would limit future damage to the nervous system. How encouraging! I am so thankful that there are so many brilliant, talented and dedicated researchers out there investigating new ways to treat MS. If any of you ( or anyone who has participated in the MS trials) are reading this, I THANK YOU. It's because of your dedication that I can have hope for my daughter's future.

I just spotted an article: www.elan.com/News/full.asp?ID=578660
that state that an application was recently submitted to the European Medicines Agency for approval of Antegren. This is encouraging. My daughter, age 21, was recently diagnosed with MS. At her neurologist follow up appointment today, her doctor told us that hopefully next year, this drug would be available for her. She's currently on Rebif; the doctor said she'd switch her over to Antegren because she felt she'd be an excellent candidate for it. Looking at the limited information on how this med works, it appears as if it would limit future damage to the nervous system. How encouraging! I am so thankful that there are so many brilliant, talented and dedicated researchers out there investigating new ways to treat MS. If any of you ( or anyone who has participated in the MS trials) are reading this, I THANK YOU. It's because of your dedication that I can have hope for my daughter's future.

I just spotted an article: www.elan.com/News/full.asp?ID=578660
that state that an application was recently submitted to the European Medicines Agency for approval of Antegren. This is encouraging. My daughter, age 21, was recently diagnosed with MS. At her neurologist follow up appointment today, her doctor told us that hopefully next year, this drug would be available for her. She's currently on Rebif; the doctor said she'd switch her over to Antegren because she felt she'd be an excellent candidate for it. Looking at the limited information on how this med works, it appears as if it would limit future damage to the nervous system. How encouraging! I am so thankful that there are so many brilliant, talented and dedicated researchers out there investigating new ways to treat MS. If any of you ( or anyone who has participated in the MS trials) are reading this, I THANK YOU. It's because of your dedication that I can have hope for my daughter's future.

I just spotted an article: www.elan.com/News/full.asp?ID=578660
that state that an application was recently submitted to the European Medicines Agency for approval of Antegren. This is encouraging. My daughter, age 21, was recently diagnosed with MS. At her neurologist follow up appointment today, her doctor told us that hopefully next year, this drug would be available for her. She's currently on Rebif; the doctor said she'd switch her over to Antegren because she felt she'd be an excellent candidate for it. Looking at the limited information on how this med works, it appears as if it would limit future damage to the nervous system. How encouraging! I am so thankful that there are so many brilliant, talented and dedicated researchers out there investigating new ways to treat MS. If any of you ( or anyone who has participated in the MS trials) are reading this, I THANK YOU. It's because of your dedication that I can have hope for my daughter's future.

I just spotted an article: www.elan.com/News/full.asp?ID=578660
that state that an application was recently submitted to the European Medicines Agency for approval of Antegren. This is encouraging. My daughter, age 21, was recently diagnosed with MS. At her neurologist follow up appointment today, her doctor told us that hopefully next year, this drug would be available for her. She's currently on Rebif; the doctor said she'd switch her over to Antegren because she felt she'd be an excellent candidate for it. Looking at the limited information on how this med works, it appears as if it would limit future damage to the nervous system. How encouraging! I am so thankful that there are so many brilliant, talented and dedicated researchers out there investigating new ways to treat MS. If any of you ( or anyone who has participated in the MS trials) are reading this, I THANK YOU. It's because of your dedication that I can have hope for my daughter's future.

Hello all - I found this site and the thread on Antegren for MS. I am following this closely as I have had MS for almost 10 years now and sure could use some new treatment options.

I saw some postings on the board regarding chemotherapy and Novantrone. I must tell you that I had a very successful outcome with Novantrone. I am relapsing remitting, but in 2000 I was heading downtown with a spiral of repeated flareups and steroid treatments. Novantrone shut down the entire process and is the reason I am still able to walk, work, raise my kids and live a normal life. Although it was chemotherapy, I did not get sick, did not lose hair and did not suffer any fatigue or low blood counts. I have been off the therapy for one year now and my old symptoms and fatigue are returning.

So my suggestion to those out there that have an impression that chemotherapy is very very bad stuff, I would leave you with this thought. If you have MS your immune system is already working at a higher level than it should. Immunosuppression, through steroids or Novantrone, tamps down an overactive immune system. Check it out - talk to oncologists about chemotherapy (not neurologists) because they know these chemo agents well and can tell you that Novantrone is a relatively safe chemo agent to use in the small doses and limited regiment for MS. Check it out, it might work for you.

It is so nice to meet you all and find this discussion.

I am not diagnosed with MS but, it is a possibility that my doctors are looking in to. I had an MRI which showed two legions on my brain. However, because I suffered from head trauma in '94, (and ironically, there's no record of an MRI being done at that time), they are using this MRI as a baseline and will continue to monitor my brain with follow-up MRIs. (They are assuming that the legions are from the trauma.)

The pain, weakness, and fatigue that I have dealt with for about seven years now, has only been worsening. Many tests have been done, many things have been ruled out. Right now, my doctors have me on an antidepressant and Tizanidine. This combo has been very helpful, more-so than anything that's been tried in the past.

But, I would still like to know what is wrong with me...ya know? I'd like to put a name on this...even if it is MS, because then at least we can form a good treatment plan.

The not knowing can be so hard I know and yes there can be comfort in knowing just what you're dealing with. Fortunately, research has come a long way in the last few years so stay tuned, help is on the way.


"Let a smile be your umbrella!"

I'm just finishing a Phase III trial on Antegren, and I feel as though I'm the lucky one. I was diagnosed in 2001, and I've never been on any other medications other than steroids for several exacerbations. I'm about to go into the "open label" period where I will definitely be getting the drug regardless of whether I may have been getting the placebo before. From what I've heard, there really are very few side effects. Certainly I haven't experienced any, but that could mean that I'm on the placebo. I haven't minded the monthly infusions at all, either. I'd much rather face a needle once a month than every day or every other day. I've even become horseback riding buddies with a couple of the infusion center nurses. I hope your daughter gets access to Antegren if she wants it; I really have faith that this is going to be a good medicine.

My mother has been diagnosed with ms since 1994. She has been on most of the medication that there has been available to the communities, and now in December she will be on the Antegren. I think that it will be a lot better for her, because I know that she is getting tired of taking the Copaxone shot everyday... To anyone out there who doesn't even understand, or hasn't seen someone with this very dibilitating disease, please come spend some time in my shoes... Seeing someone that you love and admire losing the ability to walk and knowing that there is nothing that you can do but watch the disease progress is horrible...She didn't like the Avonex because she wasn't able to do anything after taking the shot because it made her feel like she had the flu, and when you have little children, it is no fun having them watching because you can't get out of bed because of the symptoms that it causes.