This isn’t a fragile X trial, but the same Neuren compound that is in trials now for fragile X (NNZ-2566) has shown significant positive effects in a Phase 2 trial for Rett syndrome.
The results of the trial are interesting, in that improvement was seen a Rett syndrome-specific rating scale compared to placebo, and there was also improvement noted on the CGI-I (Clinical Global Impression of Improvement) and Caregiver Top 3 Concerns. However, there was no effect seen on ABC scores (Aberrant Behavior Checklist) compared to placebo. Many in the fragile X field have noted the inadequacies of the ABC; indeed, it was never designed or intended to be an outcome measure for clinical trials. In this case, a Rett-specific rating scale called the Motor-Behavior Assessment (MBA) showed a statistically significant and clinically meaningful treatment effect at the highest dose of the Neuren compound compared to placebo.
This is great news for those of us in the fragile X field for several reasons. First of all, it shows that this compound really does something---it seems to have useful properties in actual patients, and that’s not trivial. Second of all, this result demonstrates that disease-specific symptoms can improve significantly on the drug, and that improvement can be measured in a relatively short clinical trial. Additionally, it shows that a drug can have beneficial effects on core features of a genetically based developmental disorder, even if the more general rating scales (like the ABC) show no change. This is strongly reminiscent of the experience of many families and clinicians in recent fragile X clinical trials, where the drugs showed no advantage compared to placebo, but genuine improvement was noted in many subjects, with significant deterioration upon discontinuation of the drugs. Thus the calls for improved rating scales which can “capture” these core, disease-specific therapeutic effects. The Neuren fragile X trial is using some fragile X-specific outcome measures which will hopefully lead to similar positive results. The fact that this result is good news for Neuren also means that the company should remain financially viable for longer, so that they can continue the development of this compound for a number of indications---more “shots on goal”.
Of course, the usual caveats apply: this was a small study, and these results need to be replicated in a larger Phase 3 trial. Still, there’s a realistic possibility that we may see a similar result in fragile X!