The high-profile failures of various Alzheimer's drug candidates in recent months has dampened some of the buzz around the disease, and particularly the beta-amyloid hypothesis. Nonetheless, the enormous cash prize awaiting the developer of a cure means that many companies continue plugging away in the understandable belief that the gamble is still worth taking.
A safer bet might be the pursuit of diagnostic technologies. One PET imaging agent, Eli Lilly's (NYSE:LLY) Amyvid, has already passed regulatory muster in the US and is set for European approval this year. Now GE Healthcare (NYSE:GE) is muscling in with its tracer [18F] flutemetamol, and has taken the unusual decision to seek approval in the US and the EU simultaneously. With GE already a huge player in the imaging space, this two-handed approach might give the wherewithal to beat the frontrunner.
Whether amyloid plaque buildup is a cause or consequence of Alzheimer's - or neither - continues to be the subject of much discussion. It is, though, a largely accepted biomarker for the disease.
Amyloid plaques are found in almost all Alzheimer's patients, but can also be seen in non-sufferers. Consequently, PET tracers such as flutemetamol and Amyvid are designed to be used to rule Alzheimer's out; if no amyloid is present the patient is given the all-clear. If the test comes up positive patients are sent for further tests.
Arguably this means that sensitivity is more important than specificity. GE's tracer does not have a great record here: the company says that flutemetamol has a specificity of 99-100% but a sensitivity of just 75-100%, meaning that it will fail to detect amyloid in up to 25% of cases. Fortunately for GE, Lilly's rival product is even worse - data from one phase III trial of Amyvid indicated specificity of 90-100% and sensitivity of 69-95%.
The trouble is that imaging agents of this kind are all dressed up with nowhere to go; what is the use of a test when neither Alzheimer's nor the similar cognitive disorders that could also account for a patient's symptoms can be treated?
Reimbursement is also an issue - Amyvid is not covered by Medicare (Without payer support beta-amyloid tracers will languish, April 16, 2012).
Cunningly, GE has found a way to monetise flutemetamol before it has even gained approval. The company has licensed it three times over - to Merck & Co (NYSE:MRK), Johnson & Johnson (NYSE:JNJ) and an unnamed company - to help guide drug development. In Merck's case it will be used to help identify patients who might benefit from its Alzheimer's candidate MK-8931. MK-8931 is in phase II/III trials, and is the most advanced beta-secretase inhibitor in development (Merck & Co puts its faith in amyloid beta hypothesis, December 4, 2012).
Amyvid is likely to have sales of $85m in 2018, according to EvaluatePharma's consensus data. If its gamble comes off, GE Healthcare could be on course to beat that.