Eli Lilly said today it is halting development of enzastaurin (LY317615 HCl) after it failed the Phase III PRELUDE study, which assessed the drug candidate as a monotherapy in the prevention of relapse in patients with diffuse large B-cell lymphoma (DLBCL)—the pharma giant’s fifth Phase III failure in the past year.

Enzastaurin failed to show a statistically significant increase compared to placebo in disease-free survival in patients at high risk of DLBCL relapse following rituximab-based chemotherapy, according to a summary of topline results from PRELUDE disclosed today by Lilly. Safety data was consistent with previously disclosed studies, and no new safety issues were raised during PRELUDE, the company added.

Lilly said in a statement that it plans to present data from the Phase III trial “at an upcoming scientific meeting.”

“We are disappointed in the results that we’re announcing today,” Richard Gaynor, M.D., vp, product development and medical affairs for Lilly Oncology, said in a statement.

In scuttling enzastaurin, Lilly torpedoed plans disclosed just last month in its first-quarter results to pursue FDA marketing approval for the drug—one of five drugs for which the company had been expected to seek approvals this year.

Enzastaurin’s failure follows one Phase III trial flop earlier this year and three last year. In February, Lilly halted development of tabalumab for moderate-to-severe rheumatoid arthritis in patients who have not responded adequately to methotrexate therapy, though the company said it was continuing a separate Phase III trial of the drug candidate for systemic lupus erythematosus.

Last year, Lilly Alzheimer’s disease drug candidate solanezumab failed in two Phase III trials. But the Amyloid beta (Aß) monoclonal antibody remains under Phase III investigation, since the company said it will launch by the third quarter conduct a new Phase III study of the drug in patients with mild Alzheimer’s.

Also failing in Phase III last year was Lilly’s schizophrenia candidate pomaglumetad methionil (mGlu2/3), which also failed to meet its primary endpoint in a Phase II study.

Lilly’s pipeline issues come as the company braces itself to lose most of the nearly $5 billion it racked up last year on sales of Cymbalta due to its U.S. patent expiring in December. Three months later, in March 2014, Lilly’s U.S. patent on Evista will also expire, taking with it much of the drug’s $1.01 billion in 2012 revenue.

“However, our oncology pipeline is still one of the most robust across the industry containing more than 20 molecules, including two Phase III molecules in five different tumor types,” Dr. Gaynor said in the statement.

Those two Phase III molecules are necitumumab, indicated for squamous non-small cell lung cancer; and ramucirumab for breast cancer, colorectal cancer, and gastric cancer. Lilly said in January it lost Bristol-Myers Squibb as a partner in developing necitumumab for North America and Japan.

Enzastaurin is an oral small molecule that works by acting as a serine/threonine kinase inhibitor of the PKC beta and AKT pathways.

Lilly said it will take a charge against its R&D expense of about $30 million in the second quarter, but will not change its investor guidance on 2013 earnings.

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