Alcobra releases new neuroimaging data supporting pro-cognitive effects of MDX

TEL AVIV, Israel—Alcobra Ltd., an emerging pharmaceutical company focused on the development of new medications to help patients with cognitive disorders, including Attention Deficit Hyperactivity Disorder (ADHD) and Fragile X Syndrome, today released topline results from a pharmacological MRI study designed to evaluate the regions of the brain that are modulated by MDX (metadoxine). The study evaluated brain response to a single administration of metadoxine in rats. The experiment included three treatment arms: a placebo group, a low-dose group (corresponding approximately to the 700mg MDX dose in humans), and a high-dose group (corresponding approximately to the 1400mg MDX dose in humans). Neuronal activity was examined by evaluating blood oxygen level dependent (BOLD) MRI imaging, which measures brain oxygen levels that are related to changes in brain nerve cell activity. BOLD phMRI was employed to study 170 different areas of the brain following placebo or drug administration.

The results showed that Metadoxine produced a significant, dose-dependent decrease in BOLD signal in highly selective regions of the brain, including the prefrontal cortex, and showed a statistically significant increase in BOLD response in brain regions, including the central nucleus of the amygdala and the lateral hypothalamus. In addition, none of the mesolimbic dopamine system brain regions (such as the nucleus accumbens), known to be involved in the reinforcing effects of scheduled drugs, were significantly affected by Metadoxine at any dose level, which is consistent with previously presented data.

"Metadoxine produced a specific and extensive effect in brain areas related to executive function, learning and memory, motivation, information integration and processing, attention and cognition," said Dr. Jonathan Rubin, chief medical officer of Alcobra. "A functional decrease in these neuronal circuits mediated by MDX may help ADHD patients filter unnecessary sensory stimuli. These findings also confirm and extend previous data demonstrating a novel monoamine-independent mechanism of action of Metadoxine characterized by GABAergic inhibitory transmission modulation."

According to analyst The Motley Fool (TMF), there are three stocks to watch in the changing landscape of ADHD drugs. A March report from pharmacy benefit manager Express Scripts revealed that U.S. prescriptions for adult attention deficit hyperactive disorder drugs rose from 1.7 million in 2008 to 2.6 million in 2012— a 53 percent increase. That study, which analyzed 15 million privately insured people under the age of 65, also uncovered an 85 percent increase in use of ADHD drugs among women between the ages of 26 and 34.

Some medical experts believe those figures indicate that ADHD drugs are being overprescribed, while others argue that prescriptions have risen due to an increased awareness of the disorder. “Despite the controversy that surrounds these medications, health-care investors should be aware of the key differences between ADHD drugs, and three companies in the field that are providing treatments: Shire, Johnson & Johnson and Alcobra,” TMF stated.

According to TMF, Shire's three main ADHD drugs—Adderall XR, Vyvanse, and Intuniv—generated $519 million in combined sales in the last quarter, accounting for 40 percent of the company's top line.

Johnson & Johnson's Concerta's main patents won't expire until 2017 and 2018, but generic versions have nonetheless been approved. After a court ruled that one of Concerta's patents was invalid in 2009, J&J reached agreements with Watson (now known as Actavis), Impax Laboratories, and other drugmakers to manufacture generic versions of the drug. Those generic versions have taken a bite out of J&J's pharmaceutical revenues.

According to TMF, last quarter, Concerta sales fell 41 percent year-over-year to $150 million, due to competition from generic drugs. In 2013, sales fell 27 percent to $782 million -- a steep drop from the $1.3 billion in sales that it generated back in 2010.

Johnson & Johnson's involvement in the ADHD market doesn't end with Concerta, however. Its antipsychotic drug Risperdal has also been prescribed to children with ADHD in the past. That practice, along with several other controversial uses, led to a $2.2 billion fine for J&J last November for the improper off-label promotion of the drug to children and adults.

Alcobra's experimental drug Metadoxine Extended Release, or MDX, is a nonstimulant treatment being tested for predominantly inattentive ADHD, which accounts for 40 percent of all ADHD cases, and Fragile X syndrome, a genetic syndrome that causes autism in boys. MDX was shown to be effective and well tolerated in two Phase 2 studies of adults with ADHD. It has begun enrolling patients in a Phase 3 trial, with completion expected in the second half of this year.

“The market for ADHD treatments might initially appear saturated with generic drugs, such as cheaper versions of Shire's Adderall and J&J's Concerta. However, Shire and Alcobra show us that there's still room for improvement in the market. Shire's Vyvanse shows that new formulations of stimulants can be less habit-forming than older ones, while demand for non-stimulants like Intuniv and Strattera remains high. That means there's still room for newcomers like Alcobra to find space in this market with newer nonstimulant treatments,” the analyst firm concludes.

Alcobra Ltd. is an emerging pharmaceutical company primarily focused on the development and commercialization of a proprietary drug candidate, MDX (MG01CI), to treat cognitive disorders including Attention Deficit Hyperactivity Disorder (ADHD) and Fragile X Syndrome. MDX has completed multiple Phase 2 studies in adults with ADHD and has completed enrollment in a Phase 3 study in adults with ADHD. The company has also begun separate Phase 2b trials in pediatric ADHD and in adolescents and adults with Fragile X Syndrome.