Eli Lilly: Disappointing data does not deter focus on beta amyloid.
Alzheimer’s disease is one of the most challenging therapeutic targets to be pursued in pharmaceutical R&D. While research into this disease therapy has been somewhat successful in terms of developing symptomatic therapies, there has been a track record of failures for disease-modifying candidates such as bapineuzumab (Johnson & Johnson/Pfizer). Moreover, there is still plenty of deliberation among the scientific community over the actual pathogenesis of Alzheimer’s disease and the different approaches to targeting its complex underlying mechanisms. However, mindful of the significant revenue potential of Alzheimer’s disease treatment, Eli Lilly is firmly betting on the beta-amyloid approach. This strategy is risky, but Lilly hopes to achieve the high returns that it needs in order to offset one of the largest patent cliffs among big pharma.
On Friday 12 July, Eli Lilly announced details of a planned third Phase III study to further investigate the disease-modifying effects of Alzheimer’s therapy candidate solanezumab. The EXPEDITION3 trial will focus on patients with mild Alzheimer’s that have been pre-screened using Amyvid (florbetapir F 18 injection), a beta-amyloid positron emission tomography (PET) imaging agent used to detect the presence of beta-amyloid plaque in the brain. Eli Lilly gained rights to Amyvid through the acquisition of Avid Radiopharmaceuticals for $300m in 2010.
It is hoped that solanezumab, if approved, would represent the first disease-modifying Alzheimer’s disease drug, providing short-term symptomatic benefits and slowing the progression of the underlying disease, to enter the market. Solanezumab is a humanized version of mouse antibody m266, a monoclonal antibody that recognizes a specific beta amyloid’s epitope. It is hoped that binding and removal of soluble beta amyloid by the drug could lead to the dissolution of beta-amyloid plaques and result in slowing of the disease progression.
Lilly recently linked the somewhat unimpressive clinical results obtained from the two earlier EXPEDITION trials to the hypothesis that about a quarter of enrolled patients might not have had beta-amyloid deposits or Alzheimer’s disease and, therefore, the Phase III monoclonal antibody could not have shown an effect on these patients. Furthermore, the two previous studies also recruited patients with moderate Alzheimer’s disease, in whom it is thought to be much harder to demonstrate clinical efficacy via an amyloid-targeting mechanism. While a pooled analysis of mild patients from EXPEDITION yielded a statistically significant 34% reduction in cognitive decline, it is feared that such modest activity of solanezumab may not be sufficient to secure an approval and subsequent reimbursement. By adopting a more targeted approach, such as eliminating potential non-responders or patients that do not have beta-amyloid plaques and focusing on patients only with mild Alzheimer’s disease, the company hopes to established stronger clinical evidence in order to support a regulatory submission.
Unfortunately for Eli Lilly, Amyvid has recently endured setbacks itself. On Wednesday 3 July, the Centers for Medicare & Medicaid Services (CMS) issued a draft decision against coverage of the diagnostic tool, proposing that further evidence from additional trials would be necessary for a positive recommendation. A final decision is expected in October 2013. Of note, a positive test from the $3,000-per-patient adjunctive diagnostic tool does not establish a diagnosis of Alzheimer’s disease, as stated on the product’s label. Amyvid can be used instead to rule out patients that do not have the disease on the back of a negative test – which explains why Amyvid could prove to be a useful addition to the EXPEDITION trial, but will struggle as a standalone product.
Eli Lilly faces a challenging outlook as upcoming patent expiries are set to erode revenues. Despite efforts to advance its late-stage assets, Datamonitor Healthcare forecasts Eli Lilly’s prescription pharmaceutical sales to drop over 2012–18 at a compound annual growth rate (CAGR) of -3.7%, seeing a net decline in sales of $4.2bn.