HEALTH: Second Alzheimer’s Drug To Slow Disease’s Progression May Be Approved In The US This Year

By Meg Tirrell, CNN/StyleMagazine.com Newswire

Thefull approval this month of the Alzheimer’s drug Leqembi marked a historic shift in the treatment of the disease: For the first time, doctors have a medicine to prescribe that has been proven to slow the loss of memory and ability to do daily tasks that Alzheimer’s brings.

A second drug may join Leqembi — known as lecanemab before it got its brand name — on the market by the end of the year: Eli Lilly’s donanemab.

It was shown in May and in fuller Phase 3 clinical trial results released at the Alzheimer’s Association International Conference on Monday to delay the disease’s progression. Lilly said in a news release that it had completed its US Food and Drug Administration submission for the drug, and expects regulatory action by year’s end.

More than 6 million Americans are estimated to have Alzheimer’s disease, with about 1 million estimated to be in the early symptomatic stages where these drugs have shown benefit. But even though the medicines are the first to put a brake on the seemingly inexorable progression of Alzheimer’s, experts questioned the degree of their benefit in a series of editorials published Monday in the Journal of the American Medical Association, alongside the donanemab data.

Both Leqembi and donanemab work by clearing buildups of a protein in the brain called amyloid, a hallmark of Alzheimer’s.

“Donanemab was very effective at eliminating its target, cerebral amyloid, but the clinical effect was comparatively weak,” Jennifer Manly, of Columbia University Irving Medical Center, and Kacie Deters, of the University of California, Los Angeles, wrote in one editorial.

Patients taking the medicine in the more than 1,700-person trial had 35% slower progression of disease than those on placebo over a year and a half on a measure called the integrated Alzheimer’s Disease Rating Scale, or iADRS, the results showed. That equated to a loss of six points on a 144-point scale for those on the drug, compared with a loss of nine points for those on placebo.

In another editorial in JAMA, researchers sought to put that result and others from the trial into real-life terms: For patients taking donanemab, there’s a lower risk of progressing from having mild cognitive impairment, or being fully independent in daily activities, to mild dementia, requiring assistance with some daily activities; or of progressing from mild to moderate dementia, requiring some assistance with basic self-care.

Lilly assessed patients in groups based on their levels of another Alzhei- mer’s-associated protein, called tau, and the 35% slowing of disease progression was seen in those with low to medium levels, thought to be in less advanced stages of the disease than those with higher levels. When those with higher levels were included, the benefit was 22% versus placebo.

Unlike Black adults, the study found that White adults living in communities with a high proportion of redlining did not have a higher risk of heart failure.

“These findings show us the harm that discriminatory and racist housing policies have had on generations of Black adults and suggest the long-term impact of such policies on cardiovascular health disparities,” said Dr. Ambarish Pandey, another co-author and an assistant professor in the Department of Internal Medicine at UT Southwestern Medical Center.

For patients in the low/medium tau category, the researchers pointed out the drug slowed decline by 4.4 months over the 18-month trial on the iADRS scale. On another scale, known as Clinical Dementia Rating-Sum of Boxes, or CDR-SB, it slowed decline by 7.5 months.

“While the slowing of clinical decline seen in this trial represents an important start, and may be deemed clinically meaningful for some patients, development of more impactful and safer treatments is still needed,” wrote the authors, the University of California, San Francisco’s Dr. Gil Rabinovici and Renaud La Joie.

Experts’ hesitation on the degree of benefit isn’t limited to donanemab; it also applies to Leqembi. On the CDR-SB measure of disease progression, donanemab showed a 36% slowing compared with placebo in the low/medium tau group, and a 29% slowing overall, while Leqembi, sold by the drugmakers Eisai and Biogen, showed a 27% benefit over placebo.

To Lilly’s chief of research, Dr. Daniel Skovronsky, the donanemab trial results answer some key questions, and hint toward ways to reach greater benefits for patients with Alzheimer’s.

“One of the questions we had was: Does the effect grow over time?” he said in an interview with CNN. “That’s important because Alzheimer’s disease is a chronic disease that can last a decade or more.” www.StyleMagazine.com