Eli Lilly said today its antidepressant drug candidate edivoxetine (LY2216684) failed to meet its primary endpoint in three Phase III trials of superior efficacy after eight weeks of treatment—in yet another late-stage clinical setback for the pharma giant.
Edivoxetine, when added to a selective serotonin reuptake inhibitor (SSRI), did not separate from placebo on the Montgomery-Asberg Depression Rating Scale (MADRS) in three acute randomized Phase III studies—LNBM, LNBQ, and LNBR. The Phase III trials focused on meeting unmet needs of patients with major depressive disorder (MDD) who had achieved only a partial response to treatment with an SSRI. In these trials, patients remained on SSRI treatment and additionally received either edivoxetine or placebo.
Lilly said the disappointing efficacy results, which follow three years of trials, do not support a regulatory submission for adjunctive treatment in MDD patients despite safety and tolerability levels consistent with past clinical studies. The company said it would disclose data from all three studies “in appropriate scientific forums” in 2014, and would continue an ongoing clinical study evaluating the long-term maintenance effect of edivoxetine.
"While disappointing for people suffering from depression, their families, and Lilly, negative studies are unfortunately a reality of biopharmaceutical innovation, and are particularly prevalent in the area of neuroscience given the historically high placebo response rate," Jan Lundberg, Ph.D., evp of science and technology and president of Lilly Research Laboratories, said in a statement.
Lilly will take a fourth-quarter pre-tax charge of about $15 million related to edivoxetine. The company said its financial guidance for 2013 will remain unchanged.
Credit Suisse had predicted edivoxetine would be a near-blockbuster for Lilly, projecting sales of the drug would climb to $918 million by 2020 following a launch it expected would occur in 2015.
Edivoxetine is the latest in a string of Lilly clinical trial failures in 2013—a list that includes LY2886721, a beta secretase (BACE) inhibitor evaluated as a once-daily treatment for Alzheimer’s disease; ramucirumab for breast cancer (though not for gastric cancer, where a Phase III study showed more positive results); enzastaurin (LY317615 HCl), studied as a monotherapy in the prevention of relapse in patients with diffuse large B-cell lymphoma; and tabalumab for moderate-to-severe rheumatoid arthritis in patients who have not responded adequately to methotrexate therapy (though the company said soon after that it was continuing a separate Phase III trial of tabalumab for systemic lupus erythematosus).
However, Dr. Lundberg and Derica Rice, Lilly’s evp of global services and CFO, noted the company this year overall has advanced its pipeline, which it said consisted of nine potential new medicines and diagnostic imaging agents for neuroscience-related diseases and disorders, including Alzheimer's disease, Parkinson's disease, depression, bipolar disorder, migraine prevention, and osteoarthritis pain.