Despite losing its lead Alzheimer’s disease candidate three months ago, Eli Lilly (LLY) has signaled its ongoing interest in the field with the $300m acquisition of diagnostics player Avid Radiopharmaceuticals.
Avid has already filed florbetapir, a molecular imaging agent that can detect amyloid plaque in the brain, with the FDA. If it wins approval, florbetapir would be the first proven diagnostic for Alzheimer’s in living patients. The move also underscores Lilly’s intentions in diagnostics; earlier this year a new division was formed to specifically work in this area and this acquisition could rapidly accelerate its presence.
The company believes it has established a strong correlation between florbetapir-PET scan results and the levels of beta-amyloid pathology in brains at autopsy. Although doctors can be fairly confident in Alzheimer’s diagnosis clinically, currently the only way to definitively confirm the presence of the disease is to look for the classic plaques and tangles in the brain after death.
Having a proven diagnostic test available for living patients will be a big step forward, particularly if it means the disease can be diagnosed earlier. Researchers believe the plaque and tangles can be present for a decade in some patients, before symptoms manifest.
Theoretically, the agent could also be used to monitor disease progression and possibly even drug efficacy. With numerous Alzheimer's agents in the pipeline targeting beta-amyloid, florbetapir holds the potential to become a useful tool in the diagnosis and treatment of Alzheimer’s.
Following the failure of semagacestat, Lilly has two further Alzheimer’s candidates in active development. The most advanced, solanezumab, is an antibody designed to break up the beta amyloid clumps. Two phase III trials started in May 2009 and will report next year.
Still in phase I, the company has a BACE or ß-Secretase inhibitor called LY2811376. The ß-Secretase enzyme is thought to be involved in the formation of amyloid plaques, so its inhibition could theoretically help slow or stop the disease.
The beta-amyloid theory - that these clumps kill brain cells and cause Alzheimer’s – informs the majority of Alzheimer's therapies in the pipeline (Therapeutic focus - What are plan B options if A-beta Alzheimer's hypothesis is void?, August 19, 2010).
However, this theory is far from proven. The failure of semagacestat, a gamma secretase inhibitor, certainly prompted concerns about this approach (Will gamma secretase Alzheimer's class survive the fall of semagacestat?, August 18, 2010).
Whether this theory stands or falls should not impact florbetapir as a diagnostic tool, as detecting the presence of beta-amyloid will remain a marker of Alzheimer's. It is likely to impact the agent's potential, however if evidence grows supporting the beta-amyloid theory.