Why So Many Alzheimer’s Trials Fail—And What Can Actually Move the Needle

Pintail Solutions President Jason Bork was recently published in an issue of Indiana Business journal’s special BIOFUTURES magazine. This interview series adds some additional insight beyond the article. 

In the race to treat Alzheimer’s disease, clinical trials are a necessary—but often flawed—part of the journey. Despite billions invested, many trials end in disappointment. In this conversation, Jason C. Bork, President of Pintail Solutions, breaks down the reasons for those failures, the promise of emerging technologies, and the critical need for inclusive recruitment and strategic site selection.

Interviewer:
Nice to see you as always, Jason.

Jason C. Bork:
You as well. Thank you.

Interviewer:
I want to talk a little bit about your feature in bio futures, if you don't mind. Why do so many Alzheimer's trials fail? And what strategic changes can improve success rates?

Jason C. Bork:
Yeah, that may not be the right question—but there are lots of reasons for drug failures, and lots of reasons for Alzheimer’s trial failures. For one, especially with the brain, we don’t understand the pathology as well as we’d like. We know that amyloid plays a role. We know tau does too. But there are different subsets and aspects of both amyloid and tau. There’s just a lot we still don’t know.

Everyone wants to launch a drug. Everyone wants to improve or prevent the disease. But the truth is, most of the benefit and contribution people are going to make is through what we learn in drug failures. Better understanding the science. Better understanding the biology, the pathology.

I really suspect we’ll get to a place where treating Alzheimer’s becomes personalized. We’ll see drug cocktails—some targeting amyloid, some targeting tau, and maybe others focused on neuroinflammation or mitochondrial function. But there’s still a lot we are left to understand in that world.

Interviewer:
So, Jason, how can new tools, innovation, and technology accelerate or de-risk the clinical development process?

Jason C. Bork:
There are a lot of ways to answer that question—and I imagine we’ll touch on more of them later. But identifying the right trial sites is absolutely critical.

We’re seeing exciting developments in emerging technologies like digital biomarkers, blood-based biomarkers, and ocular scans. A lot of this tech isn’t brand-new anymore, but it’s also not fully regulatory-approved yet. Still, it’s good enough to help prescreen participants and improve screen fail rates.

As you may know, many Alzheimer’s trials have screen failure rates of 85 to 95%. And the failures often occur at the most expensive stage—like PET scans, which can cost up to $10,000 per participant. You don’t want to pay $10,000 per person for 100 people just to find 5 who qualify for your drug.

These new technologies might introduce some data bias, but if they’re truly predictive—and many are—they can have a big impact on improving trial efficiency.

Interviewer:
Can we talk a bit more about the challenges of recruiting for clinical trials?

Jason C. Bork:
Absolutely. As I mentioned earlier, it starts with identifying the right sites. You need to understand your patient population, understand how trial sites have performed in that population in the past, and understand what’s changed at those sites.

Beyond that, you need to go beyond your current database. You’ve got to be creative and novel in how you engage with communities. We call it going “out in the wild.” It’s about finding new ways to reach people and invite them into potential studies.

A lot of sites we work with are open to collaboration. They believe that if you can make the pie bigger, everyone wins. It’s not just about fighting over slices of a small pie. Unfortunately, Alzheimer’s is extremely common in America and globally—so the need is there.

That’s a critical issue. In Alzheimer’s disease, Black, African-American, and Hispanic populations have nearly twice the risk of developing the disease. Yet in most trials, they’re significantly underrepresented. The numbers are so low, it’s almost embarrassing to quote them.

There are a few key problems. Pharma and biotech companies often build everything around their trial. But for many underrepresented communities, showing up for 15 minutes, saying hello, and running a study for three months—or even two years—isn’t enough.

If you want participation from underrepresented groups—and you should, because the FDA expects it more and more—you need long-standing relationships in those communities. Or you need to partner with people who already have them. That’s absolutely vital moving forward.