The goal of finding an effective disease-modifying therapy for Alzheimer’s disease by 2025 will not be reached without a shake-up of the drug development process, says a new report.
The stark conclusion is that the target will be missed without improvements in clinical trial design and biomarkers, the creation of patient registries to improve trial recruitment, more sensitive clinical assessment tools and faster regulatory review.
The report – authored by a working group of prominent experts in Alzheimer’s research – notes that for approval by 2025, potential disease-modifying therapies need to be in late phase I now, and most compounds with a chance of success by that date will likely be in phase II or III testing.
Given that there are only around 25 compounds in phase I at the moment, and the high rate of pipeline attrition, “it is likely that only a few compounds could possibly reach this milestone” with current development and regulatory pathways, they write.
With exploding rates of the disease around the world, a lack of effective drugs will create a massive problem for already-stretched healthcare systems. By 2030 it is estimated that there will be almost 75 million people with dementia, and the cost of caring for these individuals could rise to some $2trn.
There are no therapies currently available to slow the inexorable decline in memory and cognition caused by the disease, though treatment with neurotransmitter-modulating drugs can temporarily improve symptoms. In the absence of disease-modifying therapies, the estimated number of people with dementia will reach more than 131m by 2050.
“If we do not take immediate action to address the way we approach Alzheimer’s disease, we will be doing a disservice not only to the many people around the world who are or will be impacted by this devastating disease, but also to our health care systems,” says lead author Jeffrey Cummings of the Cleveland Clinic Lou Ruvo Center for Brain Health in the US.
Among the suggestions put forward by the working group are that the phases of clinical trials should be merged to shorten study timelines, and that healthcare professionals should be mobilised to prepare databases of healthy aged and symptomatic individuals who can take part in trials.
There should also be a comprehensive effort to see if existing drugs – such as statins, antihypertensives, cancer treatments and anticonvulsants – can be repurposed to treat Alzheimer’s.
Encouraging earlier diagnosis will be crucial, they suggest, as current clinical assessment tools are not good enough to detect early signs of the disease. More sensitive measures that can help pick up subtle clinical declines among people with minimal symptoms are needed.
Changes to the regulatory environment are also warranted. Accelerated regulatory review processes, alignment of clinical trial endpoints with disease stage, and pivotal studies that test multiple patient populations could all expedite drug approval.
In particular, the researchers suggest it may be advisable to consider drug approval based on a cognitive outcome only rather than cognition and function in these earlier stages of disease as is the norm at present.
That recommendation in particular will be welcomed by Eli Lilly, which is awaiting the first results from its EXPEDITION-3 trial of amyloid-inhibiting drug solanezumab before the end of the year.
The company tweaked the design of the study midway to focus on cognitive rather than functional outcomes, which at the time led to speculation that it was concerned it would not meet the more stringent objectives.