Advances in Alzheimer's drug development offer hope for patients

Dr. Jeffrey L. Cummings, UNLV research professor and a leading expert on Alzheimer's disease clinical trials, led a five-year review of all Alzheimer's drugs in the development pipeline. He says today there is more hope than ever that we'll one day solve Alzheimer's.

The paper, "Alzheimer's disease drug development pipeline: 2020," was published this week in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.

The first time his team published an analysis of experimental drugs in 2014, they quantified a 99 percent failure rate of all therapies in the pipeline. It was the first analysis of its kind and has proven enormously popular with roughly 67,000 downloads and 260 citations.

Currently, there are 121 unique therapies in 136 clinical trials in the pipeline. We recently met with Cummings from the UNLV School of Integrated Health Sciences to understand what has changed in the world of Alzheimer's drug development over the last five years.

Tell us about this five-year review. What is its primary purpose?

We want to continue to analyze how the ecosystem and process of drug development is working over time to accelerate getting treatments to patients. I have been involved with clinical trials for the past 20 years and there have been very few studies showing how the process of drug development works. To get a treatment for patients, it's a complicated process involving many entities along the way including labs, biotech firms, pharmaceutical companies, the federal government, and the marketplace. Scientists, funders and, ultimately, patients want to understand what potential therapies are being developed.

What are the key takeaways over the past five years of the drug development pipeline?

We have yet to have a successful drug move across the finish line since our original publication in 2014. It is striking that there has been an increase in the number of repurposed agents compared to five years ago. Several drugs approved to treat other conditions are now being tested to see if they work for Alzheimer's disease. There are several benefits because the drug's properties and safety issues are already known.

Another thing we learned is that patient participation is critical and recruitment is too slow, challenging, and expensive. A typical drug trial lasts 18 months and the patient recruitment period may be two years longer than it takes to show efficacy. The company funding the trial has to pay expenses the entire duration, which can mean $30 million to $50 million or more per trial.

Does this mean there aren't any new drugs in the pipeline?

There are new drugs but not as many as we need to advance toward our goal of meaningful therapy for patients. The expense of developing new drugs is exorbitant. It can be $400 million for an entire development program. Currently, there are an estimated 100 million Americans suffering from at least one brain disorder, including Alzheimer's, costing the health care system nearly $790 billion annually. Investment in new and innovative approaches is needed from public and private funders to help us solve these problems for millions of people.

Thankfully, the Alzheimer's Association has stepped in to fill part of the gap. Many funding initiatives -; specifically their International Research Grants Program and Part the Cloud -; were created to fund much needed novel therapies.

How has the recent discovery of new biomarkers impacted the pipeline?

This is an exciting development that offers hope for successful Alzheimer's treatments. In the past two years, several new biomarkers [a measurement, like a blood test, that reveals what's happening in the body] for Alzheimer's have been developed and some have been approved for use by the FDA, which means we can offer a more precise clinical trial process. We can now use biomarkers to better define our patient populations. It is something new, precise and powerful.

Recently, you proposed a new scoring method for the pipeline to determine readiness to move from one phase to the next. What inspired you to do so and what are you hoping to achieve?

We know there is a 99 percent failure rate of drugs in the pipeline. Translational scoring addresses issues in the testing process with rigorous criteria that can consistently be applied to all the therapies in development. The result is a semi-quantitative rating that shows the flaws in a drug development program early on. This is especially critical information for a funding agency to compare treatments to each other and to understand which drug is least risky.

What is your team at UNLV focusing on?

The recently established Chambers-Grundy Center for Transformative Neuroscience in the department of brain health is focusing on analyzing clinical trial methods to see which strategies, what targets, and what biomarkers are succeeding and how we can use these lessons to get better drugs to our patients faster. For me, this is enormously exciting.

How optimistic does this make you about conquering Alzheimer's?

We've never seen more promise in the pipeline than there is today. The very recent discovery of relevant biomarkers allows us to develop drugs with a precision we've never had before. We are going to solve this problem.

What can real people do to help advance the science of Alzheimer's treatments?

We are working with our patients and families to solve the brain disease they have. We can have success only if they participate in the clinical trials. There is a critical alliance between the scientists, a patient, and their family to accelerate drug development. We need our "citizen scientists" because they are contributing in such an important way to a future without Alzheimer's disease.

As a researcher yourself, where do you learn about other's work?

The upcoming Alzheimer's Association International Conference is the major information sharing opportunity among Alzheimer's disease researchers across the world each year. It's an enormously important conference where we share and learn about each other's work. I am presenting at four sessions -; virtually this year given the pandemic -; and am looking forward to hearing ideas from new researchers to senior ones like myself. Since it is virtual, it is offered at no cost and open to everyone.