Eli Lilly’s donanemab appears to delay cognitive decline in Alzheimer’s patients, but it can have very serious side effects.
A new drug against Alzheimer’s in an advanced stage of experimentation would seem to slow down the cognitive decline characteristic of the disease and allow patients more time to carry out small everyday actions independently. The drug, a monoclonal antibody called Eli Lilly donanemab it is not – it should be clarified immediately – a cure for Alzheimer’s, but only a way to delay its progression, and in the face of potentially very serious side effects.
However, if the results, for now announced only in a press release, were confirmed in scientific studies in peer reviewcould represent a new possibility to contrast the symptoms of the most common form of dementia, which affects around 600,000 people in Italy alone, with another 3 million people more or less directly involved in their assistance.
A brake on symptoms. Much like lecanemab, another monoclonal antibody under US FDA approval, donanemab targets amyloid beta protein plaques, extracellular protein deposits thought to cause neurons to malfunction, and then die.
The drug binds to plaques and facilitates their elimination. In the trial, which involved a total of over 1,700 patients with the first symptoms of the disease, the drug slowed cognitive and functional decline (i.e. the decrease in potential physical capacity) by 35% compared to placebo.
What did the study find. As explained on Scienceslowed the progression of Alzheimer’s was found in two different evaluations, which monitored the progress of the patients’ physical and cognitive functions over 18 months compared to the control group.
Initially we wanted to understand how taking donanemab, which is administered by infusion, impacted the ability to autonomously carry out daily life tasks such as driving or preparing a meal – operations that were measured through the Integrated Alzheimer’s Disease Rating Scale (iADRS). Compared to this scale, the phase 3 trial which included 1,182 patients showed a 35% reduction in the rate of decline over 18 months compared to placebo.
Compared to another more widely used scale – the Clinical Dementia Rating-Sum of Boxes o CDR-SB, which collects clinical and caregiver assessments to assess the severity of dementia – slowing of disease progression was 36%. Eli Lilly also reported that symptom severity remained stable for one year in 47% of treated patients; the same happened in only 29% of patients who received a placebo.
Better performances? Based on these data, the new drug would appear to be more effective than lecanemab, even if it is very difficult to compare them since no studies have been done that directly compare them. The trials involved different populations of patients with disease at different stages (those who took lecanemab had less severe symptoms) and were designed and conducted differently.
Adverse effects. As for side effects, the drug was as dangerous, if not more, than lecanemab. 24% of patients who received it experienced cerebral edema (a serious condition consisting of the accumulation of fluid and pressure on the brain tissues), while 6% reported symptoms such as confusion, headaches and fainting .
31.4% of the treated group also had microbleeds, compared with 13.6% of the placebo group. Both of these conditions, edema and microhemorrhages, are also possible symptoms of Alzheimer’s disease. But the dangerousness of the side effects requires reflection cost-benefit which will affect doctors, patients and caregivers.
The amyloid hypothesis. Finally, an important aspect beyond the clinic concerns the research on the still mysterious causes of Alzheimer’s. The fact that another drug directed against amyloid plaques, besides lecanemab and aducanumab, appears to slow the symptoms of the disease reinforces the common and disputed hypothesis that preventing the accumulation of amyloid protein helps to stem the progression of this form of dementia.
According to the proponents of this hypothesis, the results would indicate that the beta-amyloid it is if not the main, at least a significant factor in the origin of Alzheimer’s. And perhaps this generation of risky and expensive drugs will inspire a future one, less dangerous and affordable for everyone.