Arimocolomal did better than a placebo at slowing the decline in patients with a rapidly worsening disease, although the differences were not statistically significant, researchers said. It was also safe, and patients tolerated it well, CytRx reported.
The study, “Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS,” was published in the journal Neurology.
Arimoclomol promotes the correct folding of proteins. This means it could be used to treat patients with SOD1 gene mutations, the second most common cause of ALS.
The mutations lead to a version of the SOD1 protein that is prone to misfolding and clumping. The faulty protein then accumulates in nerve cells.
Researchers recruited patients with rapidly worsening ALS stemming from SOD1 mutations for the Phase 2/3 trial (NCT00706147). The Phase 2 portion focused on arimoclomol’s safety and patients’ ability to tolerate it. The Phase 3 portion addressed its effectiveness.
A key effectiveness yardstick was whether arimoclomol could increase patients’ survival. Another was whether it could slow patients’ rate of functional decline.
Researchers used two functional decline measurements. One was patients’ scores on the Revised ALS Functional Rating Scale. Another was a barometer of lung function decline known as FEV6, which looks at how much air patients can expel in six seconds after a deep breath.
A combo measure that researchers used was the Combined Assessment of Function and Survival.
The team randomized the 36 participants so that 17 received arimoclomol and 19 a placebo three times a day for up to 12 months.
Safety was assessed with three yardsticks — number of adverse events, abnormal lab test results, and abnormal vital signs.
The arimoclomol and placebo groups had roughly the same number of adverse events, and most were unrelated to treatment. Most were also mild.
Abnormal lab test and vital sign results were rare and occurred at comparable rates in the two groups.
Arimclomol performed better than the placebo in effectiveness measures, although the differences were not statistically significant.
The functional decline in the arimoclomol-treated patients was 2 1/2 points per month on the Revised ALS Functional Rating Scale, versus 3 points per month for the placebo group. The difference in decline was more pronounced in patients with the A4V form of ALS, which progresses particularly rapidly. The drop was 2.6 points a month in the arimoclomol group, versus 3.6 points in the placebo group.
Researchers saw the same kind of differences in the lung function parameter FEV6.
While the effectiveness results were not statistically significant, “the consistency of results across all pre-specified efficacy measures suggests a possible therapeutic benefit of arimoclomol in the overall study population, and especially in the A4V subgroup,” the researchers wrote.