Andrew N. Wilner, MD; Mark S. Freedman, MD

Disclosures

April 30, 2012

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Editor's note:

At the 64th Annual Meeting of the American Academy of Neurology in New Orleans, Louisiana, Dr. Andrew Wilner interviewed Dr. Mark Freedman, Professor of Neurology in the Department of Medicine at the University of Ottawa, on promising new therapies for multiple sclerosis (MS). Is MS care in for a sea change?

Andrew N. Wilner, MD: Hello. I am Dr. Andrew Wilner. Welcome to the 64th Annual Meeting of the American Academy of Neurology, here in New Orleans, Louisiana.

I am here today with Dr. Mark Freedman. Mark is Professor of Neurology and Director of the Multiple Sclerosis Clinic at the University of Ottawa in Ontario, Canada.

At this meeting, we are seeing a lot of new data on MS. Mark is going to be kind enough to help us sort that out.

Mark S. Freedman, MD: Thanks, Andy. It is an exciting meeting for us. Many years, we don't have a lot of news, but this year we have been anticipating a lot of the results from the trials that have been ongoing now for almost the last 3-4 years, heralding a new era of treatment with drugs that are now available as oral agents. Up until now, everything has been injected. It has created some problems with patient adherence to medication. It is so much easier to take a tablet. But the big questions are, will these tablets work, will they be safe, will they be equally effective to what we have had for the last 20 years? This is what the big anticipation is all about.

Dr. Wilner: That is very exciting and good news for patients. It is making doctors' lives a little more complicated. We are going to have to learn how to choose and how to make recommendations. Are there new data this week? What do we know this week that we didn't know last week?

Dr. Freedman: These data have been trickling through the various meetings that we have had in the past year or so. We have been anticipating the confirmatory studies. We have heard the first study results with molecules such as BG-12.

Dr. Wilner: That is a pill, right?

Dr. Freedman: That is a pill.

Dr. Wilner: Another oral.

Dr. Freedman: That particular agent has to be taken at least twice a day. The studies were 2 times and 3 times daily for a couple of years. The first study was very successful, very promising, with good treatment effect. But with event rates so low these years in our patients, authorities are almost always asking for a confirmatory study because even the placebo patients are doing phenomenally well. The event rates are extremely low in terms of relapses. The confirmatory studies are hopefully going to show exactly the same effects, if not better.

The additional demand that has been imposed by the European authorities is that in order to get some idea of how the new medicines are going to fare relative to the ones we have had for the last 20 years, add an active comparator, which is a little bit novel for MS studies because usually you want to do a randomization to the various treatments, including the comparator. But that is not what they asked.

The blinded comparison, with patients not knowing whether they are taking placebo or drug, is the old, traditional way. But then there is an open-label comparator in which patients are on one of the approved therapies to get an idea of how the 2 populations, followed prospectively, would do.

Those are the results that we have seen this week with BG-12. They used glatiramer acetate as a comparator. Laquinimod was another pill that came out. They used interferon-beta-1A as a comparator. Then we have the monoclonals, which are very exciting in themselves because alemtuzumab, which is a once-a-year treatment, didn't even use a placebo and used the high-dose interferon-beta-1A as a direct comparator. It was clearly a superiority type of trial.

I can just summarize all the results. They are all positive. The comparator sometimes underwhelmed in a couple of the trials. Then you are really tempted to say that the new medicine is better than the comparator, but, of course, that can only be done if you really randomize the patients in a properly controlled trial. But you can at least see in real time what the differences might be when you use the new product vs the old one.

Then the question is really safety. No really huge safety issues have come out that we haven't heard about already. It's a very exciting time and the tool chest is getting bigger and fuller, which is going to make life more complicated for physicians.

Dr. Wilner: What is the timeline? What is the first new drug that we are likely to see and have to learn about in terms of how to dose it and what to look for? Of course, we don't know. It requires US Food and Drug Administration (FDA) approval, but I believe that BG-12 now has completed 2 phase 3 trials. Are there any other ones that are on the road?

Dr. Freedman: Yes. The other big one is teriflunomide. Teriflunomide has been in study over a decade, actually, much longer than BG-12, although BG-12 is based on a product that has been available in Europe for years, in generic form, for the treatment of psoriasis. There is a big question here as to how different this BG-12 is compared with the generic form in Germany. Is it going to warrant the cost difference? That is another question. Teriflunomide has been around for about a decade in an MS study. They have now done 3 studies. One of them you have only heard about -- it's not being presented here -- is an effectiveness trial. Efficacy and effectiveness: a little different question here.

Dr. Wilner: Tell us the difference.

Dr. Freedman: Efficacy is, the people who take the product -- how did they do vs the people who didn't take it? What if you couldn't handle the product? What if you couldn't stay on the product? Isn't that a worthwhile question? When you throw a drug out into the community, people will only benefit from the drugs they actually take, right? Effectiveness has to measure the ability of an individual to stomach it and stay on it, and then they reap the benefits. This study was actually compared with one of the interferons. It showed that, in fact, the advantage of the pill superseded any potential efficacy of the interferon beta. I think teriflunomide is going to have an interesting play, and it has an incredibly good safety record and is very easily tolerated. You are going to see BG-12 vs teriflunomide.

The player that came in a year ago, fingolimod, is still there but, of course, with some safety issues, and is now probably relegated to the second tier. Then there are 2 or 3 fingolimod look-alike drugs that are all in phase 2 trials that we are hearing about this week, all moving into phase 3 trials in the coming year. It is really getting full.

Dr. Wilner: Why is this happening? How come, for so many years, we just had a few injectable drugs, the interferons, and all of a sudden now there are 5, 10, and maybe more drugs that are approaching FDA approval? How did that happen?

Dr. Freedman: We have had these discussions before. There have been a lot of failures, if you recall. There have been a lot of attempts at trying to develop new therapies that just didn't pan out in phase 2 studies or, in early phase 3, had a problem and had to be pulled. We heard about cladribine a few years ago. Unfortunately, safety issues forced the company to pull that and they are not going to market it. There haven't been as many successful agents. This is very exciting because all of these drugs work differently and they may have certain advantages for particular patients. Just like a good tool chest, you are not going to fix everything with a hammer. You need a few other tools, and this new array of medicines -- we haven't even talked about the monoclonals -- is going to give us that fuller tool chest of things to choose from.

Dr. Wilner: The basic science research that is going on in understanding neuroimmunology is really step 1. That has made a big difference, hasn't it, in the development of these drugs?

Dr. Freedman: Huge. Absolutely. As we become more understanding of the steps that have taken place, technology has allowed us to say that if that stuff is important, here is something that works there. Then you can follow on, develop a therapy. That is exactly what has happened.

Dr. Wilner: Mark, I want to thank you very much for giving us the highlights of the new drugs. It looks like it is a very exciting time for doctors and for patients with MS. They are going to do better.

Dr. Freedman: I agree. It is a great time to be in the field. Thanks, Andy.

Dr. Wilner: Thank you very much for listening to Dr. Freedman inform us of some of the exciting new developments in the field of MS, presented here at the American Academy of Neurology meeting in New Orleans, Louisiana. I am Dr. Andrew Wilner. Thank you for watching Medscape.

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