Alcobra's drug misses the mark in Fragile X trial after flunking in ADHD

Alcobra's ($ADHD) lead drug failed to help patients with the rare Fragile X disorder focus their attention in a Phase II study, a clinical setback that comes on the heels of a Phase III failure in attention deficit hyperactivity disorder.

The treatment, MDX, didn't meet its primary endpoint in a 62-patient Phase II trial on Fragile X, a genetic disorder that often leads to autism and ADHD. In the 6-week study, Alcobra's drug fared worse than placebo in improving patients' scores on the Attention Deficit Hyperactivity Disorder Rating Scale, a composite of cognitive symptoms, the company said.

The problem, according to Alcobra, may have stemmed from the fact that many patients took other ADHD drugs during the study and were randomized without balance, inflating the efficacy of placebo. And the company turned its back on its primary endpoint, saying after the fact that ADHD-RS has serious limitations when applied to patients with widely varying intellectual capacities.

But the secondary endpoints, against which MDX succeeded, are better indicators of efficacy, according to Alcobra. The drug significantly improved patients' results on 5 other measures of cognitive ability, including the Vineland Adaptive Behavior Scale, and the biotech is now blueprinting a Phase III trial with that as the primary endpoint. The plan is to meet with the FDA in the coming months before embarking on a new MDX study, the company said.

The Phase II failure sent Alcobra's shares down as much as 20% on Wednesday morning, coming just months after the company's top prospect missed the mark in a mid-stage ADHD study. In March, Alcobra disclosed that MDX failed to beat placebo in improving attentiveness among pediatric ADHD patients in a Phase II trial. Last year, the same drug failed in a Phase III study on adults with ADHD.

In each case, Alcobra has touted secondary endpoints, modified analyses and vague signals in its defense of MDX's promise. And the latest failure hasn't dissuade management from pressing forward with the drug, a nonstimulant GABA modulator the company bills as free of the abuse potential that plagues other treatments for ADHD.

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