On 17 January, Alcobra announced that its extended release formulation of the drug metadoxine failed to meet the primary end point in its pivotal Phase III trial MEASURE, where it was administered to children, adolescents, and adults with ADHD.
The results of this study showed that metadoxine was no better at controlling the symptoms of ADHD then a placebo, according to the Conners Adult ADHD Rating Scale (CAARS).
This has not been the only setback in the development of metadoxine. The MEASURE clinical trial was put on hold in September 2016 due to concerns over damaging effects on peripheral nerves in animal studies. The significance of this was played down at the time, as metadoxine was administered at much higher doses in this study. In December 2016, the hold was lifted.
This recent failure has rocked the small Israeli-based company, as its extended release formulation of metadoxine would have helped Alcobra to establish itself in the neurology drug market. The drug is a monoamine independent gamma-aminobutyric (GABA) modulator with a unique mechanism of action (MOA), targeting GABA transporters and inhibiting the activity of degradation enzymes. This is said to lead to cognitive regulation.
This unique MOA and the wide patient population would have meant metadoxine would have carved out a valuable niche for itself in a market dominated by reformulations of already existing drugs with identical MOAs.
Alcobra CEO Yaron Daniely addressed shareholders after the failed trial and stated that the results are seen as conclusive and metadoxine will not be marketed as a drug for controlling ADHD symptoms. This leaves the company at a crossroads on what to do next.
The immediate-release formulation of metadoxine has been on the market for more than 30 years for alcohol intoxication and alcoholic liver disease. It has an excellent safety and tolerability profile. As such, Alcobra is likely to focus its research and development (R&D) efforts on developing metadoxine extended release for the rare disease Fragile X Syndrome, given it has completed Phase II trials in this indication. However, the drug already faced a mid-stage study failure for Fragile X Syndrome in 2015.
GlobalData believes that for the drug’s launch to be a commercial success, Alcobra will need to partner with a large, well-established pharmaceutical company to ensure a global reach.