Every 66 seconds someone in the United States is diagnosed with Alzheimer’s disease (AD) and by 2030, it’s estimated that 75 million people worldwide will be affected. The implications of this devastating disease reach far beyond those afflicted, causing turmoil both socially and economically. This growing health crisis is referred to as the “grey tsunami” and carries an estimated cost of $1 trillion — a financial burden no government can bear.
With the grey tsunami an eminent threat lurking on the horizon, the Obama Administration and several other member nations attending the 2013 G8 Dementia Summit established a goal of developing a meaningful treatment for AD by 2025. Since then, we have been in a race to develop a cure or treatment and the stakes couldn’t be higher.
The clock is ticking. In an effort to better understand where we are at in the AD drug development process, I — along with fellow colleagues at Cleveland Clinic Lou Ruvo Center for Brain Health as well as researchers from Touro University and Global Alzheimer’s Platform — have begun a yearly analysis of the AD drug pipeline.
The results of our second assessment were astonishing and published in the paper titled “Alzheimer’s Disease Drug Development: Pipeline 2017” in the Journal of Alzheimer’s & Dementia: Transitional Research & Clinical Trials Interventions. Our study found that there is an urgent need to enhance the drug development process in order to optimize our chances of success. To progress drug development, immediate action is needed to increase the number of agents entering the pipeline to accelerate the drug testing process.
Using the advanced search mechanisms of ClinicalTrials.gov, a government website that records all ongoing clinical trials by law, we examined all clinical trials from 2016 to 2017 and found that the number of agents in the pipeline is small — 105. In addition, compared to the 2016 pipeline, there are only eight new agents in phase one, illustrating a desperately slow period in AD drug development.
At this rate, to meet our 2025 goal, an agent must currently be in the second of three phases of drug development. The third phase leads to FDA review and possible approval. Given the state of the pipeline, the approval of one or two drugs is plausible, but the goal of developing an effective treatment or prevention for many of the AD population and those at risk is in jeopardy.
In addition to high drug failure rates, we also uncovered several obstacles that inhibit drug development, which include: slow clinical trial recruitment and drug testing as well as a lack of sufficient funding. Currently, the National Institute of Health spends an annual $6 billion on cancer research, more than $4 billion in heart disease research, $3 billion on HIV/AIDS research and less than $2 billion on AD research. Cleveland Clinic believes we must address these inhibiting factors in order to increase the success rate and accelerate the development of new therapies.
So what can be done to improve the drug testing process? The answer: a lot. Our paper serves as a call to action and notes several areas we believe can significantly advance drug development. As one of the leading research institutes, the Lou Ruvo Center for Brain Health is ready to help orchestrate the changes needed and the time do so is now.
Our first recommendation is to increase the testing of repurposed drugs, which involves studying an already FDA-approved drug in a new use or condition. Many repurposed drugs have mechanisms of action that are worthy of exploration in AD. Because we know they have had success in certain areas, we are encouraged to test their abilities in other areas. For example, anti-hypersensitive agents, statins, anti-inflammatory agents and calcium channel blockers have been proposed as drugs that could possibly have effects useful in treating AD. Because all of these agents have already been FDA approved, they can skip phase one of clinical trial testing and are allowed to enter the drug pipeline at phase two or three. This ultimately speeds up the drug development timeline. However, there are only a modest amount of repurposed drugs in the AD drug development pipeline (18 in phase two and six in phase three) and this is partially due to lack of biopharma interest in testing these drugs.
A striking observation we found when conducting our analysis is the anticipated recruitment time for clinical trials. Slow clinical trial recruitment is arguably among the greatest challenges in AD drug development. Often times, the anticipated recruitment time is longer that the treatment period of clinical trials and planned recruitment goals are not met. This is because we experience difficulties in recruiting participants that meet the qualifications needed for specific trials. In fact, 20 percent of people who have been diagnosed with AD do not actually have AD, which is an inhibiting factor in clinical trial recruitment. As of now, a staggering 54,073 participants are needed to complete the current list of AD trials. The recruitment of such a larger number of potential participants will be slow and expensive and is a substantial challenge in the drug development process. Reforms are necessary to accelerate clinical trials and enhance recruitment and one way to do this is to utilize biomarkers.
Biomarkers are disease indicators that help us better understand the makeup and intricacies of the disease. Biomarkers have many roles in clinical trials, including identifying appropriate patients for trials, confirming a diagnosis, serving as outcomes for therapies and assessing side effects. Biomarkers are critical to the process as they illustrate what a drug is doing and serve as an intermediate step that tells us if the drug is doing what we want it to do in humans. At this time, it is unclear how many clinical trials are currently using biomarkers as not all descriptions on ClinicalTrials.gov indicate if a biomarker was used. In addition, we know that many drugs are missing targeted biomarkers. Given the significance of their role in drug development, it is clear that we need to continue to implement the use of biomarkers as they can contribute substantially.
The solution to several of the obstacles faced in the AD pipeline can partially be addressed by an increase in funding. Investment in basic research will assist in identifying more targets and compounds, while investments in translational research can help support clinical trials and improve trial methods. Funds from federal small business loans, venture capital and philanthropy are all used today to support drug testing, but are not sufficient enough to address the urgent need. New investment vehicles are needed and some have been proposed such as private-federal bonds. Insurance companies that stand to benefit from improved health of the elderly should be engaged in funding conversations, while new types of collaborations such as the National Institute of Health and biopharma companies can increase the feasibility of bearing the expenses of AD drug development and enhancing the chance of success.
The need is great, the challenges are many, the rewards are high — this is the status of the AD pipeline. As a scientist I remain hopeful that an effective treatment is insight because there has never been a greater, more coordinated effort to develop a cure. Amazing work takes place daily at the Lou Ruvo Center for Brain Health and we are on the forefront of ground-breaking research that will no doubt, impact the world.