Ask the Doc: Q & A with Edward Kasarskis, MD, PhD

Edward Kasarskis, M.D., Ph.D. is Director of the multidisciplinary ALS Center at the University of Kentucky Neuroscience Center in Lexington, Kentucky, professor in the Department of Neurology at the University of Kentucky, and Chief of Neurology at the VA Medical Center in Lexington KY. 

	Dr. Kasarskis

Q: I’m taking Rilutek now but am wondering what else might be on the horizon in terms of potential drugs for ALS?

A: That’s a great question. There are several high-potential drugs being tested right now through clinical trials.

By the way, the drug you’re taking, Rilutek (riluzole) has been around for about 20 years now.  You should know that the American Academy of Neurology’s 2009 Practice Parameters say that the drug is effective in slowing the rate of progression of ALS. Some physicians may downplay the benefits and potential impact of Rilutek, but it’s important to know that it does play a role in treating ALS. It is not a perfect drug, and so the quest for additional drug treatment continues.

When thinking about the future of drug therapy for ALS, most experts agree that the most effective treatment will likely be a “drug cocktail,” combining two or more medications, rather than taking just one.  This may ultimately be our best strategy in treating the disease.

There are a large number of clinical trials in progress right now testing drugs, stem cells, and gene therapy that could change the course of the disease and preserve or improve muscle strength. Here’s a quick update:

• Dexpramipexole by Biogen Idec: This drug looks promising. It is believed to work by increasing the efficiency of mitochondria the power houses of cells in motor neurons.
  
  The drug is a three-dimensional mirror image of a current treatment for the symptoms of Parkinson’s disease (Pramipexole). The chemical difference in structure may make "Dex" less likely to have unwanted side effects that some people with Parkinson’s experience with the parent drug.  A small Phase 2 trial of the drug in 102 newly-diagnosed people with ALS showed improvement in functional capability and survival.
  
  A Phase 3 trial with almost 1,000 people enrolled should be completed very soon.
  
  If, and this is always a BIG IF, this drug proves successful and is approved, it’s likely that it would be taken along with Rilutek.
  
  
• Ceftiraxone: We just learned a few of months ago that a clinical trial was halted because the drug proved to be ineffective in a pivotal Phase 3 trial.  This was a complicated and very long study, and was particularly disappointing since there was a lot of good scientific support for this approach.  I know I speak for all the members of the study teams in thanking the patients and their families for their devotion to getting an answer. It was truly an amazing effort lead by Drs. Cudkowicz and Shefner, and supported by the National Institutes of Health.
  
  
• CK2017357 (Tirasemtiv) by Cytokinetics: This drug increases a muscle’s strength when it contracts and might decrease fatigue. It has the greatest impact on what is described as mid-level exertion, such as walking, reaching and talking. CK2017357 appears to reduce fatigue and improve function in people with ALS. This drug, now in a Phase 2 trial, would also be used with other medications. It looks pretty promising.
  
  
• NP001, by Neuraltus Pharmaceuticals: Results from a Phase 2 clinical study of NP001 were released this fall (on the eve of Superstorm Sandy, as it turns out, so you probably didn't read about it) and just reported at the International ALS/MND Symposium in Chicago last week. The study showed that 27% of patients who received this drug had no progression of their disease during the six-month period they were taking the medication. That means that twice as many people experienced no disease progression as compared to those who were taking a placebo (an inactive drug). The trials were conducted at 17 sites across the country, involving a total of 136 patients. People were randomly assigned to get a low dose, a high dose or a placebo. We participated in both the Phase 1 and Phase 2 trials of NP001 at the University of Kentucky.

Dr. Bob Miller, the principal investigator of the study, described the study results as "encouraging" in a Neuraltus press release: “Halting the rate of disease progression, in a subset of patients, as this study suggests, would translate into a clear clinical benefit for these patients,” he said.  I agree completely. Unfortunately, rather than being an oral drug, the medication is given intravenously over several days at a time, for a period of months. The next step: a more definitive Phase 3 trial is likely to be started in 2013.  

If you’re interested in participating in a clinical trial in your area, visit www.clinicaltrials.gov.  There is much work to be done.

UPDATE: Feb. 6, 2013

This update is regarding one of the medications I discussed above, Dexpramipexole, by Biogen Idec. It looked very promising and I mentioned that a Phase 3 trial was expected to be completed very soon. I wanted you to know that, unfortunately, the trial was not successful. There was great hope that the drug would be effective in slowing ALS based on the preliminary studies. But in the end it did not turn out to be the case. This serves to remind us all that a clinical drug trial is, at the end of the day, an experiment. Some drugs succeed and others will fail. But the research effort must continue!

If you would like to submit questions for a future Q & A, please send your questions to theexchange@alsa-national.org. Please understand that we won’t be able to address all questions and we won’t be able to respond to individuals personally.