After enduring months of criticism about its late-stage effort to determine the efficacy of the last big Phase III hope for Alzheimer's, Eli Lilly ($LLY) this morning announced that solanezumab flunked both primary endpoints. The failure, widely forecast by a long lineup of analysts, will raise more doubts about the theory that cutting levels of toxic amyloid beta in patients with mild to moderate Alzheimer's can help patients with the disease.
Lilly, though, isn't giving up on the drug, its second major try at treating Alzheimer's. CEO John Lechleiter, who has bet his job that the company's R&D division can develop a new generation of therapies, noted that a secondary analysis of pooled data "showed statistically significant slowing of cognitive decline in the overall study population of patients with mild-to-moderate Alzheimer's disease. In addition, pre-specified secondary subgroup analyses of pooled data across both studies showed a statistically significant slowing of cognitive decline in patients with mild Alzheimer's disease, but not in patients with moderate Alzheimer's disease."
"We recognize that the solanezumab studies did not meet their primary endpoints, but we are encouraged by the pooled data that appear to show a slowing of cognitive decline," said Lechleiter in a statement. "We intend to discuss these data with regulatory authorities to gain their insights on potential next steps."
Expectations for this trial were so low that Lechleiter's hopeful note apparently captured the attention of investors, who initially pushed up shares of the company by 5% in early trading. A failure had been expected to trigger a sharp drop in company shares.
Why the rise? Any drug found even marginally useful in slowing cognitive decline would quickly garner megamarket revenue as desperate patients and their families await some kind of new drug. The only other treatment now in late-stage testing is Gammagard. Other therapies are being studied but are at best years away from the market.
Secondary analyses won't be any use in seeking an approval for solanezumab, though. By the time the data were in, most analysts following the company had concluded that the drug had virtually no chance of success. Just weeks ago Pfizer ($PFE) and J&J ($JNJ) wrote off their late-stage work on bapineuzumab, their own expensive effort inspired by the amyloid beta hypothesis. (A spokesperson for the company notes, though, that other Alzheimer's studies are continuing, including Phase II studies with ACC-001/vanutide cridificar (active immunization) as well as the Phase II neuroimaging study with bapineuzumab delivered subcutaneously.) The R&D focus now is likely to center on preventing the disease in high-risk patients or among people who still have a very early stage of the disease, before it damages the brain.
The failure of solanezumab is also likely to inspire a considerable amount of soul-searching about the future of Eli Lilly. Lechleiter has been one of the primary critics of the megamerger approach to restructuring a company facing a huge loss of revenue as drugs lose patent protection. The Phase III debacle will likely spur fresh calls for a fundamental change of approach, which could threaten the tenure of its CEO.
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A glimmer of hope for Alzheimer's?
With input from John Carroll, Scott Hensley and John LaMattina
On the other hand, this was a failure (secondary analyses aside). Does CEO Lechleiter have to go?
With input from John Carroll, Elizabeth Lopatto, Brian Bronk and others