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 Amyvid, has already passed regulatory muster in the US and is set for European approval this year. Now GE Healthcare 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, Johnson & Johnson 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).
The deal was signed in mid-December; no terms were disclosed. But if MK-8931 reaches market, flutemetamol transforms into a companion diagnostic.
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.