Eli Lilly’s experimental Alzheimer’s drug slows progression of the disease
Promising developments are arising in the search for an Alzheimer’s drug that can effectively slow the progression of this devastating disease.
According to the results of a late-stage clinical trial presented by Eli Lilly at the Alzheimer’s Association International Conference, their experimental drug donanemab has shown the potential to slow cognitive decline in patients in the early stages of Alzheimer’s. However, it is worth noting that the drug’s side effects, including brain swelling and brain bleeds, have been serious in some cases.
The trial results come shortly after the Food and Drug Administration approve another Alzheimer’s drug, Leqembi, developed by Eisai and Biogen. Leqembi is the first fully approved drug to slow the disease’s progression. Both donanemab and Leqembi are monoclonal antibodies that target amyloid, a hallmark of Alzheimer’s disease. It is important to mention that another amyloid-targeting drug, Biogen’s Aduhelm, faced scrutiny due to flaws in its approval process as revealed by a congressional investigation.
The rationale behind targeting amyloid is to slow down the disease’s progression. The recent trial results for Donanemab have robustly demonstrated this hypothesis, impressing experts in the field. Alzheimer’s disease affects approximately 6.7 million adults aged 65 and older in the United States.
In Lilly’s phase 3 clinical trial involving 1,736 patients with mild cognitive impairment or early-stage disease, donanemab slowed down the progression of Alzheimer’s by 29% compared to a placebo after 18 months. These results are similar to those seen with Leqembi, which resulted in a 27% decline over the same period. However, it should be noted that the results are not directly comparable as both drugs were not studied together in a single clinical trial.
During the trial, patients received donanemab or a placebo intravenously once a month. Cognitive decline was measured using the clinical dementia rating scale, which evaluates performance in six categories related to memory, orientation, judgment, problem-solving, community affairs, home and hobbies, and personal care. Patients in the placebo group scored an average of 2.42 on the scale after 18 months, while those receiving donanemab scored an average of 1.72, indicating a 0.7 difference or a 29% slower rate of decline.
Although donanemab does not cure the disease or improve patients’ conditions, it significantly delays its progression, which is considered clinically meaningful to patients, as stated by neurologist Dr. Ronald Petersen from the Mayo Clinic.
Remarkably, nearly half of the patients who received donanemab did not show signs of cognitive decline in the first year. The benefits of the treatment appeared to continue throughout the trial, even after many patients had stopped taking the medication when the amyloid in their brains disappeared. This raises the possibility that patients may be able to temporarily suspend the medication once amyloid levels decrease, reducing costs and potential side effects.
While the successes of donanemab and Leqembi provide hope for patients and their families, the potentially life-threatening side effects and high costs of these amyloid-targeting drugs remain concerns. Donanemab, in particular, has shown side effects similar to or greater than those of Leqembi, including brain swelling and brain bleeding. In the trial, approximately 37% of patients receiving donanemab experienced these side effects, and three patients died as a result.
Arthur Caplan, head of the Division of Medical Ethics at NYU Langone Medical Center, acknowledges that despite the risks, some patients and families may still choose to pursue the drug due to the devastating nature of Alzheimer’s disease.
As Lilly has filed for approval in the United States and is awaiting a response from the FDA, experts suggest that a similar boxed warning to Leqembi should be considered due to the high incidence of side effects associated with donanemab.
The search for effective Alzheimer’s treatments has seen various shifts in research direction. Following previous failures of amyloid-targeting drugs, the recent successes of donanemab and Leqembi mark a turning point in Alzheimer’s research.
Patients and their families eagerly await further developments, and ongoing trials may provide additional opportunities for treatment and hope in the fight against this devastating disease.