The ALS Association

ALS Ice Bucket Challenge Progress

News from the International Symposium on ALS/MND in Chicago

December 11, 2012

From Dec. 5 - 7, scientists from around the world gathered in Chicago, Ill. to focus on progress in hastening treatments and a cure for Lou Gehrig’s Disease at the 23rd Annual International Symposium on ALS/MND. The ALS Association is pleased to have been an official sponsor of this event. As the meeting concluded, The ALS Association’s Chief Scientist, Lucie Bruijn, Ph.D., provided an update, below on three recent clinical trials involving people with amyotrophic lateral sclerosis (ALS) presented at the symposium:

No Problems Seen for Tirasemtiv Dosed with Riluzole
The experimental symptomatic therapy tirasemtiv (formerly known as CK-2017357) can be given safely in ALS patients taking riluzole, according to a new study presented here by Jeremy Shefner, M.D., of State University of New York Upstate Medical University in Syracuse.

Tirasemtiv increases the release of calcium in the muscle during moderate contraction, augmenting strength and helping ALS patients improve their ability to carry out activities of daily living. The original study showed it to be effective as a single dose, and further studies have confirmed the benefits are maintained with more prolonged dosing, Dr. Shefner said.

Because many ALS patients take riluzole, it is important to determine whether there is any interaction between riluzole and tirasemtiv. His study showed that riluzole did not change the blood levels of tirasemtiv. However, tirasemtiv raised the levels of riluzole. Tirasemtiv inhibits the enzyme that breaks down riluzole, thereby maintaining more riluzole in the bloodstream.

The effect is not likely to be a problem for patients taking riluzole, Dr. Shefner said, as long as the dose of riluzole is adjusted to maintain the desirable blood level.

Dr. Shefner also showed data supporting a concentration-dependent effect of tirasemtiv on multiple measures of strength and ventilatory function.

A new clinical trial of tirasemtiv is currently recruiting patients. More information is available from the U.S. National Institutes of Health.

NP001 Results Hint at Benefit, But More Trials Are Needed
Intravenous infusion of the experimental drug NP001 appears to be safe in ALS patients, and some data suggest it may have an effect on progression. But the results are preliminary and should be taken with a great deal of caution, researchers said.

NP001 is a purified form of sodium chlorite, which has been shown to alter the behavior of immune system cells called macrophages. Macrophages are a normal part of the immune system, but in ALS they may change their behavior and worsen inflammation, a damaging process in ALS. NP001 blocks that change in laboratory models.

To determine its potential to aid in ALS, researchers led by Robert Miller, M.D., of California Pacific Medical Center in San Francisco, conducted a 12-month trial of intravenously delivered NP001, given monthly for the first six months of the trial.

There is no evidence that taking the drug orally can offer any benefit in ALS, Dr. Miller emphasized. Any use of sodium chlorite outside of a clinical trial is unsafe, he stressed.

In the trial, 110 ALS patients were enrolled to receive a placebo, a low-dose, or a high-dose of NP001. Neither patients nor researchers knew which patients received which treatment.

There were no statistically significant differences between the groups in any of the measures the researchers agreed to use to judge success at the start of the trial, including change in decline on the ALS functional rating scale (ALS-FRS) and measures of ventilatory (breathing) function. While there were some differences between groups in these measures, with those receiving higher doses doing slightly better than those receiving placebo, these differences were small enough that they may well have been due to chance, rather than an effect of the drug.

The researchers also made a comparison they had not planned to make at the start of the trial, called a post-hoc analysis. In this analysis, they determined how many patients in each group showed no progression at all on the ALS-FRS during the course of the study. They found that 11 percent of patients receiving placebo, 19 percent of those receiving the low dose, and 27 percent of those receiving the high dose did not progress at all. However, statistical analysis showed that even that difference could have been due to chance. Only when researchers compared the high-dose group to “historical controls,” ALS patients from previous studies, did they see a statistically significant difference in favor of the drug.

More analysis remains to be done on the data from this study. Dr. Miller was also cautiously hopeful that larger studies may show a more robust effect of treatment. However, he reiterated, there is currently no justification for use of the drug outside of clinical trials and that taking the drug orally is ineffective and not safe.

Lessons Learned from Ceftriaxone Phase III Trial, Despite Disappointing Results
Despite the disappointing outcome of the Phase III trial of ceftriaxone, the ALS clinical trials field has learned some important lessons that will aid further trials, according to lead researcher Merit Cudkowicz, M.D., of Massachusetts General Hospital in Boston.

The trial was stopped earlier this year because data analysis indicated it was not effective at changing the rate of progression of ALS, despite earlier results from a smaller Phase II trial that suggested it could.

One important advance made in the trial was that researchers gained confidence that at-home delivery of drugs through intravenous catheter was safe in ALS. Prior to this, such delivery would have been restricted to the hospital, increasing costs for a clinical trial that required this method.

This development should be valuable in future trials that require intravenous delivery, Dr. Cudkowicz said.

Information on clinical trials is made available with help from The ALS Association through the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS), which provides up-to-date information for finding both federally and privately funded clinical studies focusing on ALS and motor neuron diseases.

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