Hitting a Nerve

No improvement in sight for Alzheimer’s drug development


Another one bites the dust.

Yet another investigational agent joins intepirdine, verubecestat, solanezumab, bapineuzumab, latrepirdine, and many others on the scrap pile of research: The complete release of trial data on idalopirdine found the drug wasn’t of clinically significant benefit in Alzheimer’s disease (JAMA. 2018;319[2]:130-42).

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If Afghanistan is the graveyard of empires, then Alzheimer’s disease is the graveyard of research dollars. From 2002 to 2012, the failure rate of Alzheimer’s trials was 99.6% (Alzheimers Res Ther. 2014 Jul 3;6(4):37), compared with 87% for cancer treatment (Clin Pharmacol Ther. 2013 Sep;94[3]:329-35). It hasn’t improved since then.

The numbers are bad enough that a handful of companies, including the giant Pfizer, have decided to leave Alzheimer’s drug development entirely to focus on more promising fields. And I get that. All of us – on any exhausting, fruitless, task – will reach the point where it’s time to cut our losses and move on. I don’t blame these companies for mostly leaving the field. (Pfizer is planning to form a neuroscience venture fund to support further research.)

Optimists will argue that you still learn things from a negative trial, which is true, but nothing to date is on the immediate horizon to help. The five agents we’ve had available for the past 15-20 years are all old enough to have lost their patents, and their benefits are modest, at best.

And all this going on as the overall human population, including myself, gradually ages and dementia becomes a medical-cost time bomb on the horizon. This isn’t an American problem. Every country in the world is facing it.

Politicians love to promise hope for these things: creating fast-track programs to get drugs to market faster, finding ways to bring down costs so more people can afford them, and improving methods to treat those in need. But none of those things matter if the medications don’t work.

Many of these trials test similar molecules because the evidence to date suggests they’re targeting the cause of Alzheimer’s. But so far they aren’t working. What if, as the Firesign Theatre and others have said, everything you know is wrong?

Dr. Allan M. Block, a neurologist is Scottsdale, Ariz.

Dr. Allan M. Block

I’m not a researcher. I don’t pretend to understand why certain approaches are chosen or why they don’t work. But from my frontline office of general neurology, every failed trial makes things seem bleaker. Some families don’t even ask anymore because they see the bad news on caregiver message boards. Some, understandably frustrated, will desperately pay for worthless supplements they see advertised on TV and the Internet.

Perhaps our greatest quality as a species is resilience. We go on because we have to. The planet keeps moving around the sun as it has for almost 5 billion years, and we face tomorrow. Caregivers wake up for another day of doing their best for a faltering parent. I wake up for another day of doing my best to help them. And the researchers go back for another day hoping to find the real answer and treatment. Without trying, no treatment for anything will ever be found. We owe our patients, and ourselves, a better future than that.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

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