A new drug may slow the progression of Alzheimer's disease, but can patients get it?

It’s exciting news for Alzheimer’s patients and their families: A U.S. Food and Drug Administration (FDA) advisory panel has unanimously recommended approval of Eli Lilly & Co.’s drug donanemab. If the drug wins the agency’s approval later this year, it would be the second drug to target the amyloid plaques in the brain that are linked to the memory-devastating disease.

Still, this month has brought to mind the challenges of getting these drugs to those who will benefit most, as well as the many open questions about how best to use them.

In assessing the data on donanemab, FDA advisers didn’t focus much on whether the drug worked—the experts all agreed that the data strongly suggested it could slow the progression of the disease. They spent most of their time discussing who it worked for and how it should be used.

Questions about the use of new drugs

These questions are especially important in a field that is already grappling with new classes of drugs. As I explained last year when Biogen and Eisai’s Leqembi became the first anti-amyloid drug to receive full FDA approval, these therapies require careful, complex coordination among health care providers.

Patients require amyloid PET scans to confirm the disease, genotyping to understand the risk of side effects, regular drug infusions, and frequent MRIs to monitor for swelling or bleeding in the brain.

And while Alzheimer's disease experts are working hard to create the infrastructure to identify and treat suitable patients, the implementation of these drugs is still in the developmental stages.

"We need to find a more scalable way to make treatment available to more people," says Eric Reiman, executive director of the Banner Alzheimer's Institute.

Problems in clinical trials

There are many practical challenges to replicating Lilly's clever approach in their clinical trial.

Drug developers have a long history of improperly selecting patients for Alzheimer's clinical trials — in the early stages, they included people with general dementia but not with the specific disease we call Alzheimer's; more recently, their results were confounded by people whose disease was too advanced for the drugs to have much of an impact, or whose disease was too early and cognitive decline too slow to show clear benefit from treatment.

Lilly was looking for people in between these two groups — patients whose disease was early but advanced enough to experience worsening symptoms. To find this population, the company used specialized brain imaging to look for amyloid and tau, two signature proteins associated with Alzheimer’s that together are associated with the likelihood of cognitive decline.

But what helped prove the drug’s effectiveness also poses a challenge for its use in doctors’ offices. While amyloid imaging is becoming more widely available in the U.S., tau imaging is not. And the study didn’t have much data on people with low or very low tau levels, casting doubt on the use of donanemab in those patients.

FDA Advisory Recommendations

Ultimately, the FDA advisors concluded that all patients, regardless of tau levels, would benefit from donanemab. They also made clear that requiring tau testing to prescribe the drug would further raise already high barriers to access. The FDA should consider both of these recommendations when developing guidelines for the use of donanemab.

Lilly also studied what would happen if people stopped taking the drug after the amyloid was cleared from their brains, opening up the possibility of a limited-time treatment rather than a lifetime. In theory, less use of an expensive drug in an overburdened health care system would be a big win for patients, insurers, and the health care system as a whole.

While their results were encouraging—patients who took a placebo after their amyloid levels dropped continued to see a slowdown in disease progression—the study did not yet clarify how the approach would work in practice. For example, when and how often would special scans be needed to determine that the brain was clear of amyloid? How often would imaging be needed to catch plaques returning? And how many courses of therapy would be needed?

Long-term data and future prospects

These unknowns contrast with how Biogen and Eisai's Leqembi is being used. That treatment is currently being prescribed indefinitely.

Long-term data on both drugs will eventually help determine which of these two approaches makes the most sense. But even without that, having both drugs on the market should expand access for a patient population that has waited too long for better treatments. That’s something to celebrate.