December 20, 2012 | By Márcio Barra
After Pfizer Inc. and Johnson & Johnson Bapineuzumab failure and Eli Lilly Solaneuzumab not so great results in meeting the clinical endpoints in a phase III trial back in August, it would be expected that pharma companies would steer clear from the amyloid hypothesis which has dominated alzheimer research these last two decades. However, while other theories have re-emerged – the Tau theory, a hypothesis which states if the Tau proteins are hyperphosphorylated they can lead to the creation of tangles in brain cells –, the amyloid theory is still backed up by a number of stakeholders. Eli Lilly’s Solaneuzumab, while ineffective in lower stages of the disease, has “showed a 34% reduction in cognitive decline”, in patients with mild disease, and so many companies are focusing to create therapies that intervene before the damage is done and identify affected people much earlier, based on amyloid aggregation levels.
The question then is which theory is right? Tau, amyloid, both, none? Alzheimer’s disease is still a mystery to modern science, but these multi millions trials that are conducted, even when falling, help shed some light in the disease mechanism and pathology and help move investigation towards new developments. Phase III trials are currently underway for Rember, a drug from TauRX pharmaceuticals and the first Tau Aggregation Inhibitor. If successful in meeting the primary clinical endpoints, it’s sure to be a blockbuster. If not, investigation can move towards another hypothesis.
Another recent development, this last Tuesday, 18 December, General Electric Healthcare and Merck announced that GE healthcare will supply Flutemetamol, an imaging agent, to Merck for use in investigation regarding their Alzheimer’s disease drug MK-8931, another amyloid targeting drug that recently started a phase II/III clinical trial in patients. A global phase III trial will follow, titled EPOCH. Merck hopes to use Flumetamol, a positron emission tomography (PET) imaging agent that can detect beta amyloid in the brain, to help select patients for the trials and evaluate it as a companion diagnostic tool. This is another effort in solving the puzzle that is Alzheimer’s disease, and, like cancer, multiple pathways are sure to be involved in the disease’s pathogenesis. All theories are worth a shot.