nearly 30 years Earlier, there was an air of optimism when the first effective Alzheimer’s drug was approved. Sure, the drugs didn’t slow the progression of the underlying disease, but they did make a meaningful change in symptoms. It seemed as if someday there would be a drug that would cure the disease. “The talk was that within a few years there should be a drug that would actually interfere with the disease process,” said Rob Howard, professor of geriatric psychiatry at University College London. “I didn’t expect to have to wait more than 20 hours.”
These treatments eventually emerged in the form of anti-amyloid therapy. Anti-amyloid therapy is an antibody designed to target a protein called amyloid beta that accumulates in plaques in the brains of people with Alzheimer’s disease. In June 2021, the U.S. Food and Drug Administration (FDA) granted the antibody aducanumab preliminary approval, called early approval, but the decision has been controversial and many experts believe the drug will help patients. I believed there was no reason to think.
But with the next anti-amyloid drug, lecanemab, the situation became clearer. After a phase III trial showed that the drug moderately slowed cognitive decline as measured by the Clinical Dementia Rating (CDR) scale, a tool that assesses a person’s ability to perform tasks of daily living. , was approved in January of this year. All patients in the study experienced worsening scores over time, but those who took the drug lost 0.5 points less than those who received a placebo. And in May of this year, Eli Lilly announced that its drug donanemab appeared to slow the decline a bit longer, about 0.7 percentage points.
As expected, there is a lot of excitement about the potential to change the course of Alzheimer’s disease. However, the deployment of these drugs requires careful consideration. Since the difference between 0.5 and 0.7 points on the CDR is an average, the actual impact may vary significantly from patient to patient, and a 0.5 point difference may be too small to be meaningful. At the same time, the risks are high, and some patients may have died as a result of taking these drugs. Whether a drug with such modest benefits and significant risks is “worth it” depends in part on how much you value life with Alzheimer’s disease.
On the CDR, 0.5 points is the difference between ‘mild’ and ‘moderate’ impairment in a single domain, such as memory or community relationships. These changes may be barely observable to an outsider. In one study of patients with Alzheimer’s disease, doctors only reliably saw a patient’s difference if her CDR score changed by more than one point. However, the patient may notice things that have distracted the doctor’s attention. Julio Rojas, an associate professor of neurology at the University of California, San Francisco, said a half-percentage-point reduction in speed could allow solo driving for several more months. “It makes sense,” he says.
However, pharmaceutical companies seem to realize how unimpressive CDR numbers can be. Eli Lilly’s press release does not explicitly mention the 0.7 point benefit. Instead, the company reports that donamab slows cognitive decline by about 35 percent compared to placebo. The value of 35% can have meaning out of context. If the placebo-treated patients got worse rapidly during the study period (which they didn’t), the 35% drop could have a big impact. Leaving no doubt, the numbers could suggest a bigger impact than what actually happened.
