FDA full clinical hold throws another wrench into Alcobra’s stuttering R&D machine

FDA sign

The FDA has delivered a blow to Alcobra’s ($ADHD) faltering attempts to bring MDX to market. The latest setback sees the regulator put a full clinical hold on a Phase III trial of MDX in adult patients with ADHD, putting another barrier between Alcobra and its long-sought approval of the drug.

Officials at the FDA’s psychiatry division placed the clinical hold on MDX after getting a look at preclinical data that show “adverse neurological findings.” In a release to disclose the news, Alcobra said the FDA action wasn’t based on data from the ongoing Phase III study of MDX, a drug that has been through multiple clinical trials without raising any red flags from a neurological safety perspective.

An earlier Phase III trial of MDX in 300 adults with ADHD reported no drug-related serious adverse events. The most common adverse events were headaches, nausea and fatigue, and the figures for the placebo and treatment arms were similar. The treatment arm of Alcobra’s 62-person Fragile X syndrome clinical trial was free from serious adverse events, too.

Throughout those earlier studies, the main problem encountered by Alcobra was a lack of efficacy, rather than a nasty side effect profile. MDX has already missed the primary efficacy endpoint in a Phase II Fragile X study and Phase III adult ADHD trial, failures that have ratcheted up the importance of the program now facing a clinical hold at Alcobra.

Prior to the FDA action, Alcobra had expected to complete enrollment in the trial by the end of the year, setting it up to deliver data in the first quarter of 2017. With Alcobra sitting on cash reserves it thinks will see it through to 2018, that make-or-break readout was scheduled for well before the firm will need to raise more money.

Alcobra is now working with the FDA to get the clinical hold lifted. In Alcobra’s favor, MDX has been tested extensively in humans without alarming the regulator. And the active ingredient in Alcobra’s extended-release formulation, metadoxine, has been used safely for decades as a treatment for alcohol intoxication.