From intoxication to ADHD

TEL AVIV, Israel—Alcobra Pharmacueticals was originally created to use the compound metadoxine to make drunk people sober, but now the company has announced progress towards its new goal for the drug: treating attention deficit hyperactivity disorder (ADHD). The emerging pharmaceutical company announced data from a recent study of mice supporting a novel mechanism of action for Alcobra’s proprietary version of metadoxine, called metadoxine extended release (MDX). Unlike many common treatments for ADHD, MDX is a non-stimulant.

Alcobra’s new data show that MDX had effects on several key neurotransmitters thought to play a role in learning and memory, but not on those thought to be responsible for the side effects and abuse potential of conventional stimulant medications for ADHD. “These new data support our working hypothesis about the mechanisms underlying the observed effects of MDX on attention, learning and memory, and its attractive safety profile in human trials,” said Jonathan Rubin, chief medical officer at Alcobra.

Alcobra began shifting its focus to ADHD and similar cognitive disorders in 2010 after a pilot study of 40 adults with ADHD showed metadoxine caused significant and immediate improvements in attention tests. “Our company was originally created to develop a pill that would quickly reduce blood alcohol levels so that people could drive safely,” Dr. Yaron Daniely, Alcobra CEO, tells DDNews. “We eventually found that matadoxine was not effective at removing alcohol from the blood, but it did have a significant impact on cognitive ability, causing improvements on memory and attention tests.” Since Daniely became head of Alcobra in 2010, the company has focused on the development and commercialization of MDX to treat ADHD, Fragile X Syndrome and similar cognitive dysfunctions.

Daniely tells DDNews that MDX has the potential to offer the benefits of the existing treatments for ADHD, including stimulants such as Ritalin and Concerta, but without many of the drawbacks. While there are current non-stimulant treatments for ADHD, MDX appears to hold potential to offer higher efficacy, more rapid onset and fewer tolerability issues. “This is a rapidly effective and significantly effective drug,” Daniely says. “Its affect on attention is much more similar to stimulants than non-scheduled drugs such as Strattera.” Daniely says Alcobra expects MDX to be approved as a commercial treatment for adult ADHD in 2015 and for pediatric ADHD and Fragile X Syndrome in 2016.

The chemical metadoxine is not new to the world of medical science. It has been approved for more than 30 years as a treatment for liver disease in third-world countries. Daniely notes that studies of acute and chronic uses of the drug reveal no signs of significant adverse effects on patients. Alcobra developed a timed-release version of the substance to limit the duration of its effect on patients. The company has a patent on the drug as a treatment for neurological conditions.

Alcobra’s newly announced data come from a study of a validated mouse model of Fragile X Syndrome, a genetic condition that causes intellectual disability, behavioral and learning challenges and various physical characteristics. Fragile X Syndrome is the leading known genetic cause of autism and represents an unmet medical need and a rare disease, as defined by the Orphan Drug Act. Researchers conducting Alcobra’s study found that MDX improved measures of cognitive performance in Fmr1 knockout mice, whose behavior and brain biology mimic the phenotype of Fragile X Syndrome. These mice demonstrated improved performance on standardized tasks involving attention, memory, learning, hyperactivity and sociability. Data from the study were presented at the 69^th Annual Scientific Meeting of the Society of Biological Psychiatry. The effect of MDX on Fmr1 mice in Alcobra’s study was consistent with the drug’s effect on human adults with ADHD in previous studies conducted by the company.

The FDA granted Orphan Drug designation to metadoxine for the treatment of Fragile X Syndrome in 2013, which may allow Alcobra opportunities to move MDX through the regulatory process more quickly than usual.