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In another stinging setback, Eli Lilly's ramucirumab fails PhIII breast cancer study

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Eli Lilly announced this morning that its Phase III study for ramucirumab failed to hit its primary endpoint on progression-free survival among women with metastatic breast cancer, another stinging setback for a pharma giant that has been gambling heavily on a slate of late-stage studies to salvage its bottom line from the punishing onslaught of generic competition. A separate Phase III study for ramucirumab in gastric cancer hit its primary and secondary endpoints, but analysts were primarily focused on the outcome for the breast cancer indication.

The crucial late-stage failure--ramucirumab has been considered one of the pharma giant's top Phase III prospects--scuttles one of Eli Lilly's chief near-term hopes for a major new drug approval application. The failure also follows several years of poor trial outcomes for Lilly, which has a reputation for taking expensive and very risky chances when it comes to late-stage development. Its shares ($LLY) immediately dropped more than 5% on the news.

ISI's Mark Schoenebaum led the parade of analysts' comments this morning, noting that the Street had baked in expectations for $500 million to $600 million in annual revenue from the breast cancer indication. A number of analysts had expected the drug to clear the progression-free survival hurdle and face greater uncertainty on overall survival. Failing at PFS left several analysts shaking their heads. 

"The longer term stock impact could be greater if the Street begins to lose confidence more generally in LLY's pipeline--the Street currently carries $9 billion in probability adjusted sales for the pipeline at the end of the decade, which is 40% of sales. This is significant," added Schoenebaum. The analyst also said he was more optimistic about the outcome for lung cancer, which is expected in 2014.

Lilly's has frequently reported setbacks for its pipeline. Just a few months ago Lilly was forced to scrap a mid-stage study on a BACE inhibitor for Alzheimer's after safety fears forced investigators to shut it down. That came on top of a particularly embarrassing failure for Lilly's late-stage program for solanezumab last year and an earlier defeat for semagacestat. Outside of Alzheimer's, Lilly has had a profoundly difficult time developing new therapies. In the summer of 2012 Lilly wrote off pomaglumetad for schizophrenia after the Phase III flunked out. Its setbacks also include the failure of the Phase III tabalumab program for rheumatoid arthritis. Last fall, when a combination of Lilly's Alimta and Avastin failed for lung cancer, the company had racked up 5 straight clinical setbacks.

On a brighter note, Lilly has had a largely successful partnership with Boehringer Ingelheim, so far, on promising diabetes drugs and recently scored an unexpected success with positive results for the cancer drug necitumumab--though there are serious questions about the safety of this therapy.

Success often comes with an asterisk at Lilly these days. The giant trumpeted late-stage results for ramucirumab in stomach cancer, even though it provided only a weak 1.4 months of added survival in the study, falling shy of analysts' expectations.

"Cancer is complex and patients with different tumor types may have varied responses due to distinct tumor biologies and individual patient characteristics. Unfortunately, anti-angiogenic agents have not yet been able to demonstrate an overall survival benefit for patients with metastatic breast cancer," said Dr. John Mackey, principal investigator of the ROSE/TRIO-012 study and professor of oncology, University of Alberta.

Lilly posted its second set of positive results for ramucirumab on gastric cancer, noting successes in hitting both overall survival and progression-free survival goals.

"We are disappointed that this breast cancer trial did not meet its primary endpoint. However, now with two positive gastric cancer trials, Lilly remains confident in the overall ramucirumab development program. We are looking forward to additional Phase III results for ramucirumab in colorectal, hepatocellular and lung cancer, expected in 2014," said Dr. Richard Gaynor, vice president, product development and medical affairs for Lilly Oncology.

- here's the press release

Special Report: Eli Lilly - Biopharma's Top R&D Spenders - 2012

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