Eli Lilly has taken another big reverse step in its retreat from solanezumab, the Alzheimer’s drug once considered the company’s lottery ticket in R&D.
Following the failure of Expedition 3, Lilly’s massively expensive third attempt to come up with solid data of its efficacy, investigators have now washed their hands of Expedition Pro, another Phase III study mounted for patients with prodomal disease, when their memory begins to fade but they can still function well on a daily basis.
In a call with analysts on Tuesday, CEO David Ricks says that in light of the overlap in Expedition 3 and the Expedition Pro study, there was no scientific basis to believe they would find a “meaningful benefit to patients with prodomal Alzheimer’s disease.”
Lilly had set out to recruit 2,450 patents for Expedition Pro, which was due to wrap in 2021.
In another note, Lilly’s Q4 update included the end of a Phase I study for “A ß Antibody Fab PEG,” a new biologic entity that had been studied for Alzheimer’s disease.
Ricks took over as CEO at the start of his year, and gets to start his tenure by largely burying what remains of one of the biggest late-stage efforts in the industry, long pursued by John Lechleiter. Analysts have long been reluctant to give Lilly good odds on the drug, but in the off chance they were successful, many believed it could have racked up $10 billion in annual sales.
Instead, the drug has become the latest victim in a near complete clinical rout on the Alzheimer’s front, where researchers have been shut out of any important advances for the past decade.
Lilly is not quite finished with sola, though. The preclinical study in Alzheimer’s disease (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s “A4”), and Dominantly Inherited Alzheimer’s Disease, known as ”DIAN,” continue).
Lilly’s most advanced Alzheimer’s effort now centers on a BACE drug it in-licensed from AstraZeneca (AZD3293), to replace its own program that was scuttled by toxicity.
During Tuesday’s Q&A with analysts, Lilly chief scientist Jan Lundberg was given the task of explaining the company’s attitudes about the A beta hypothesis, which it’s been exploring for years. Sola was designed to get rid of toxic concentrations of amyloid beta, which many believe is a cause of the disease. It’s worth quoting him at length.
The amyloid-beta hypothesis and the connection to Alzheimer’s disease has strong evidence from genetics, where if you have too much amyloid in your brain, you get early Alzheimer’s disease. And also the opposite, if you have less amyloid-beta production then by mutations in the APP in the BACE1 cleavage side, you also seem to be protected from dementia.
The key question is so how do you translate then these genetics into realities of pharmacological treatment in an aged patient? And here there are a variety of approaches that have been used. And it’s also a key one here to think about if you have an antibody with access to brain, 0.1% through the blood/brain barrier, how can you compare that result then to, for instance, an oral BACE inhibitor, which some of them go 100% into the brain and are I think more likely to have a marked effect than on the free amyloid beta?
And the second question is clearly then how early do you have to treat? And I think we should recognize that even if you have mild Alzheimer’s disease, your brain has been accumulating amyloids for decades, and you almost have maximum amyloid in your brain already. So I think there could be two components here, like I say. If solanezumab really entered the brain enough to affect amyloid beta, I think our biomarkers like amyloid PET didn’t really change very much by solanezumab, nor did the actually tau then changes, which are more related to neurodegeneration change. So from that standpoint, we didn’t see any objective measures I think that we changed the amyloid content in the brain, nor then neurodegeneration.
Is this against or does this prove that the amyloid hypothesis is wrong? My view is it’s too early to say. We need to wait for even more powerful agents. And the next in turn are the oral-based inhibitors, which are more likely I think to have an even stronger effect on the amyloid beta in the brain. And in addition then, we need to look at earlier stages of Alzheimer’s.
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