Forest Laboratories, Inc. and Pierre Fabre Medicament,  the second largest independent pharmaceutical group in France, have announced the additional positive results from a phase III clinical trial of levomilnacipran, an investigational agent for the treatment of adults with major depressive disorder (MDD).

Treatment with levomilnacipran significantly reduced depression symptoms in patients with MDD compared to placebo, as measured by the Montgomery-Asberg Depression Rating Scale - Clinician Rated (MADRS-CR). This is the third, positive phase III study of levomilnacipran in adults with MDD. Further analyses of the data are ongoing. The companies anticipate filing a new drug application with the FDA in the third quarter of the calendar year 2012.

“Despite available treatment options, many suffering from major depressive disorder continue to struggle to find a treatment that works for them. This third phase III study further reinforces the potential of levomilnacipran as an effective treatment option for adults with MDD,” said Dr Marco Taglietti, senior vice president, Research & Development and President, Forest Research Institute.

“We are confident that the efficacy and safety data in these three positive phase III studies will support a successful NDA submission for levomilnacipran in MDD in adult patients. We are looking forward to working with our partner, Forest Laboratories, to file the NDA. These results confirm the relevance of our strategic choice to make neuropsychiatry a major focus of Pierre Fabre R&D,” said Frédéric Duchesne, president Pharmaceutical Division, Pierre Fabre Group.

This was a randomized, double-blind, placebo-controlled, fixed-dose study evaluating the efficacy, safety and tolerability of levomilnacipran compared with placebo in adult patients with MDD. Following a 1-week single-blind placebo run-in period, 568 men and women, 18-75 years of age, were randomized to receive either levomilnacipran 40 mg or 80 mg once daily or placebo for eight weeks. This was followed by an additional 1-week double-blind down-taper period. All patients participating in the study met the criteria for recurrent MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), and had a minimum score of 26 on the MADRS-CR. The average baseline score among participating patients was 31 on the MADRS-CR.

The placebo-corrected mean change from baseline to end of week 8 in total MADRS-CR score (primary efficacy parameter) was: -3.3 (p=0.0027) and -3.14 (p=0.0043) in the 40 and 80 mg groups, respectively. The primary efficacy analysis was performed using a pre-specified mixed-effects model for repeated measures (MMRM). Statistically significant improvement was also seen in the Sheehan Disability Scale (SDS), the pre-specified key secondary efficacy parameter (placebo corrected difference: -1.83 (p=0.0459) and -2.72 (p=0.0028) in the 40 and 80 mg groups, respectively).

Levomilnacipran was generally well-tolerated in this study. Overall, 78.5 per cent of patients completed the study. The premature discontinuation rates (all causes, including adverse-event related) were 17.2 per cent, 22.9 per cent, and 24.5 per cent for placebo, levomilnacipran 40 mg and 80 mg groups, respectively. The most common adverse events (=10 per cent and twice the rate of placebo) observed in the levomilnacipran groups were nausea and dry mouth.

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. It is an SNRI and 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 is given as a sustained-release formulation, dosed once-daily.

These study results are part of an ongoing development programme for levomilnacipran, which also includes two additional phase III studies that demonstrated statistically significant improvement over placebo. In another phase III study, levomilnacipran consistently demonstrated improvement relative to placebo over the course of the trial, however the overall difference observed between the drug-treated and placebo-treated patients was not statistically significant. Based on the overall success of the development program, the companies are preparing to file a new drug application for levomilnacipran with the US Food and Drug Administration (FDA) in the third quarter of 2012.

MDD is a serious medical condition requiring treatment, affecting more than 15 million adults in the United States yearly or approximately 7.3 per cent of the adult US population. People diagnosed with MDD may have a combination of symptoms that can interfere with their ability to work, sleep, study, eat, or enjoy once-pleasurable activities. Among all medical illnesses, MDD is a leading cause of disability in the US. The World Health Organization predicts depression will become the second leading cause of disability by the year 2020.

The Pierre Fabre Laboratories, the second largest independent pharmaceutical group in France, covers all aspects of healthcare, from ethical medicines and over-the-counter drugs (OTC) to dermo-cosmetics.

Forest Laboratories' longstanding global partnerships and track record developing and marketing pharmaceutical products in the United States have yielded its well-established central nervous system and cardiovascular franchises and innovations in anti-infective and respiratory medicine.