Forest Laboratories, Inc. (NYSE: FRX) and Pierre Fabre Laboratories today
announced that Forest has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for levomilnacipran, a serotonin norepinephrine reuptake inhibitor (SNRI) for the treatment of Major Depressive Disorder (MDD) in adults. Levomilnacipran was discovered by Pierre Fabre and jointly developed by Forest Laboratories and Pierre Fabre, under a licensing agreement in the U.S. and Canada. Pierre Fabre will be the active pharmaceutical ingredient (API) supplier.
The application includes results from three positive Phase III studies comprising two double-blind, fixed-dose studies and one flexible-dose study evaluating the efficacy of levomilnacipran compared with placebo in adults with MDD. A total of more than 1,600 adult patients received a once-daily dose of either levomilnacipran (40, 80, 120mg) or placebo in the three studies. In each of the three studies, statistically significant improvement was seen for the levomilnacipran group compared with placebo in the primary and secondary endpoints (change from baseline to endpoint in the Montgomery-Åsberg Depression Rating Scale total score and Sheehan Disability Scale total score, respectively) using the mixed-effects model for repeated measures and last-observation-carried-forward analyses.
Additionally, safety data collected from the Phase III program demonstrated that levomilnacipran 40, 80, 120mg once daily was generally well tolerated, with an incidence of adverse reactions that was consistent across the study treatment arms. The most commonly reported adverse reaction (≥10% and twice the rate of placebo) observed in the levomilnacipran group was nausea.
Levomilnacipran (1S, 2R-milnacipran), an enantiomer of racemic milnacipran, is protected by a method of use patent that extends through June 2023, without patent term extension. An SNRI, levomilnacipran has greater potency for norepinephrine reuptake inhibition than for serotonin reuptake inhibition in vitro without directly affecting the uptake of dopamine or other neurotransmitters. Levomilnacipran has been developed as a sustained-release formulation, dosed once daily.