Merck has pulled back the covers on its Phase Ib dose-escalating study for MK-8931, a BACE inhibitor for Alzheimer's which demonstrated a positive effect in reducing the level of toxic proteins flowing through patients.
The data secures Merck's ($MRK) leading position in the BACE-inhibition crowd, which includes AstraZeneca ($AZN), Eli Lilly ($LLY)--which recently had to scrap its top candidate--and others. The pharma giant has already begun a bigger, longer study for MK-8931, recruiting 200 patients for a Phase II leg which is designed to grow into a Phase III study--provided the efficacy and safety profiles stay in line with expectations.
The BACE-inhibition theory is simple. Investigators see this as a route to preventing the production of amyloid beta, a toxic protein found clustered in the brains of patients. The idea here is that if you can reduce the level of amyloid beta going into the brain, you can influence the course of the memory-destroying disease, which now afflicts millions of people around the world.
To determine if it's working, Merck checks on the flow of amyloid beta 40 and 42 in cerebral spinal fluid, key biomarkers for the study. Over the course of 7 days of treatment, investigators say they could see a noted, dose-dependent response in protein levels in the fluid. For the top 60 mg dose, investigators say they found an 84% drop in ab40, according to a spokesperson for Merck. There was an 81% drop for ab42.
Just as importantly, though, there were none of the adverse events that could destroy a drug early on, something that Lilly has just had to deal with. Lilly says that it believes the tox issues that blew up its program were related to the design of the drug, though, rather than a problem with the target itself.
Investigators in the field say that one of the chief concerns with BACE inhibition is that it raises the prospect of interfering with other functions, including myelination. Merck is also including patients with a moderate level of the disease along with patients suffering from mild, early forms of the disease, raising the prospect that they're including patients whose disease has progressed for years, causing significant and irreversible damage.
With a treasure trove waiting for any drug developer capable of developing a new drug worth approving, contenders in this field are pushing ahead as fast as possible.
"The amyloid β reduction observed with MK-8931 may offer an opportunity to further understand the role BACE1 inhibition plays in the underlying pathology of Alzheimer's disease," said Darryle Schoepp, Ph.D., vice president of Neuroscience Early Development and Discovery Sciences, Merck.
Alzheimer's has long reigned as the biggest disease target with the most consistent track record for failure. Dozens of drugs have failed in the clinic, most notably the Phase III trials for solanezumab and bapineuzumab, antibodies designed to remove the plaque from brains. Lilly, though, is going back into a third Phase III study of solanezumab after seeing a hint of efficacy in patients with mild disease.
- here's the press release
Special Reports: The Alzheimer's pipeline: What's next? | The Top Phase III Disasters of 2012
Related Articles:
Luminex to collaborate with Merck on Alzheimer's biomarker diagnostic
In Alzheimer's mystery, key biomarker will determine success of pivotal studies
Merck ignores red flags and throws dice on PhII/III Alzheimer's gamble