unmet needs in MS treatment ;Rituximab,Fumaric Acid,FTY720,Statins

Medscape discussion with Dr. Waubant


There are, at this time, no predictors of how well a patient is going to do on first-line treatment; therefore, it takes a while before declaring treatment response or failure. Identifying early predictors of the response to available MS therapies would shorten the time of exposure to an unnecessary treatment that is doomed to fail.

Also, as all of the first-line treatments are injectable there is a need to develop medications that are available orally and/or that require less frequent administration, such as intravenous (IV) alemtuzumab (Campath) (once a year or less) and rituximab (once or twice a year). This would clearly enhance treatment compliance.

The long-term safety profile for the first-line therapies, such as beta-interferons and glatiramer acetate (Copaxone), is known and is actually very good. We have approximately 15 years of follow-up for these treatments if you include the clinical trials that were performed.

Finally, the side-effect profile of current first-line therapies, such as interferons, sometimes leads patients to discontinue treatment early. Therefore, there is a need for better tolerability of these long-term therapies.

One course of rituximab decreased by 90% the occurrence of new brain lesions between months 3 and 6 after first administration compared with placebo. Also, there was a reduction in relapse rate by month 6 that was over 50% compared with placebo. Overall, the medication is well tolerated over the short term.

There was another interesting study that investigated the effect of 0.3 mg and 0.6 mg of the oral drug laquinimod on MRI-monitored disease.[5] The study showed that there was a beneficial effect compared with placebo, especially at the high dose. There was a decrease of 51% in gadolinium-enhancing lesions at the 6-month mark and a decreased relapse rate with the high dose compared with placebo. The decrease was not statistically significant, but this may have to do with the relatively small size of the study.

If some of the ongoing phase 3 studies are positive, the drugs won't hit the market probably for 3 years or so. However, we are getting closer and that is very exciting. In addition to the phase 3 trials discussed earlier, there is another oral drug of interest, BG00012 or fumaric acid that is also in phase 3 trials. Results from a phase 2b extension study were presented and the drug was shown to be safe and tolerable.[9]

It is important to remember that all of these drugs have an unknown long-term side-effect profile, especially FTY720 and laquinimod, because they are not already on the market in other indications.

There were also a fair amount of presentations regarding potential mechanisms of action and the immune effects of different drugs in development for MS, such as FTY720 and statins. There has been a fair amount of interest in using statins as immunomodulating treatments for MS, but these trials are still ongoing.

http://www.medscape.com/viewarticle/557519?src=mp