Pierre Fabre Medicament and partner Forest Laboratories reported positive topline data from a Phase III study evaluating levomilnacipran (F2695) in the treatment of adults with major depressive disorder (MDD). The study results showed that in comparison with placebo, levomilnacipran therapy led to statistically significant improvements at eight weeks in the primary efficacy endpoint of a change from baseline in the Montgomer-Asberg Depression Rating Scale–Clinician Rated (MADRS-CR) total score.
The Phase III trial involved 724 patients who met DSM-IV-TR criteria for MDD and had a minimum MADRS-CR score of 30. Participants were randomized to receive either placebo or one of three different doses of levomilnacipran for eight weeks.
The newly reported study is the second of four Phase III trials to generate results. In January Forest and Pierre Fabre announced topline data from a 362-patient eight week trial, which found that although the overall difference observed between the drug-treated and placebo-treated patients was not statistically significant, levomilnacipran therapy consistently led to improvements relative to placebo over the course of the trial.
At the time this study was reported, the partners noted that the nonsignificant results were in contrast to findings from a previous 563-patient Phase II study that demonstrated statistically significant levomilnacipran improvements compared with placebo. Two additional Phase III studies are under way. One is due to report at the end of 2011, the other before mid-2012.
Levomilnacipran is an isomer of milnacipran that acts as a selective norepinephrine and serotonin uptake inhibitor. Forest inked its deal with Pierre Fabre to develop and commercialize levomilnacipran in the U.S. and Canada, back in December 2008. Under terms of the deal Forest paid Pierre Fabre $75 million, and agreed to make future milestone payments plus royalties on sales. Forest is responsible for clinical development and commercialization of levomilnacipran in its territories, while Pierre Fabre will fund all preclinical development and drug substance manufacturing activities worldwide. If the Phase III program is successful, Forest projects filing an NDA in the U.S. during calendar 2012.
Milnaciprin has separately been developed as a treatment for fibromyalgia by Cypress Biosciences and Forest. The drug, tradenamed Savella™, was approved by FDA in January 2009. Pierre Fabre, which originally developed and markets milnacipran outside the U.S., licensed North America rights to the drug to Cypress Bioscience.