World ‘on cusp of first generation of treatments for Alzheimer’s’

The world is “on the cusp of a first generation of treatments for Alzheimer’s disease”, experts have said, as a new drug was found to slow cognitive and functional decline.

The drug donanemab, made by Eli Lilly and Company, slowed decline by 35% to 36% in a late-stage phase 3 clinical trial, the company said.

Donanemab appeared to slow the decline associated with Alzheimer’s compared with placebo in 1,182 people with early-stage disease based on those with intermediate levels of a protein known as tau.

The drug also resulted in 40% less decline in the ability to perform activities of daily living, according to the firm.

Almost half (47%) of those on donanemab had no clinical progression of disease at one year compared with 29% on placebo (defined as no decline in the commonly-used Clinical Dementia Rating Scale Sum of Boxes score).

Furthermore, participants on donanemab experienced a 39% lower risk of progressing to the next stage of disease compared to placebo, according to Eli Lilly.

In those patients receiving donanemab, brain swelling, a known side effect of drugs of this type, occurred in 24% of the participants, with 6.1% experiencing symptoms.

Brain bleeding occurred in 31.4% of the donanemab group and 13.6% of the placebo group.

Lilly said the incidence of serious brain swelling in the donanemab study was 1.6%, including two participants whose deaths were attributed to the condition and a third who died after an incident of serious brain swelling.

It said most cases of swelling or bleeds were “mild to moderate” and responded to treatment.

Daniel Skovronsky, Eli Lilly’s chief scientific and medical officer, said: “This is the first phase 3 trial of any investigational medicine for Alzheimer’s disease to deliver 35% slowing of clinical and functional decline.”

Dr Richard Oakley, associate director of research at the Alzheimer’s Society in the UK, said: “After 20 years with no new Alzheimer’s drugs, we now have two potential new drugs in just 12 months – and for the first time, drugs that seem to slow the progression of disease. This could be the beginning of the end of Alzheimer’s disease.

“Based on today’s early results, donanemab appears to slow the progression of Alzheimer’s symptoms by 36% (as compared with 27% of last year’s breakthrough drug lecanemab).

“Promisingly, the trial also demonstrated a 40% slowing in decline of everyday activities such as driving, doing hobbies and managing finances.

“While we’ve seen lecanemab could slow progression by over seven months, we’ll need to see the full results to know if donanemab could do the same or even better.”

Dr Susan Kolhaas, executive director of research and partnerships at Alzheimer’s Research UK, said: “This is incredibly encouraging, and another hugely significant moment for dementia research.

“A second drug for Alzheimer’s has been shown to slow people’s cognitive decline in a rigorous phase 3 trial. We’re now on the cusp of a first generation of treatments for Alzheimer’s disease, something that many thought impossible only a decade ago.

“The treatment effect is modest, as is the case for many first-generation drugs, and there are risks of serious side effects that need to be fully scrutinised before donanemab can be marketed and used.

“However, this news underlines the urgency of preparing the NHS to make these treatments available should regulators deem them safe and effective.

“People should be really encouraged by this news, which is yet more proof that research can take us ever closer towards a cure.”

Dr Charles Marshall, honorary consultant neurologist at Queen Mary University of London, said: “This is hugely exciting news as it provides further evidence that it is possible to slow down Alzheimer’s disease.

“When the full results are published as a paper we will be able to start carefully balancing the risks and benefits, and this will inform decisions about whether donanemab should be routinely given to patients with Alzheimer’s disease.

“For this to be possible, we will also need substantial new investment in dementia clinics that can deliver accurate diagnosis, treatments that are given as infusions, and appropriate safety monitoring.

“Without this, there is a very real risk that existing health inequalities are exacerbated as only a few patients living near large teaching hospitals will be able to benefit.”

John Hardy, professor of neuroscience and group leader at the UK Dementia Research Institute, University College London, said: “It is great news to have a success with a second anti-amyloid Alzheimer drug.

“This should dispel any lingering doubts about this approach. Having two drugs is great for competition.”

Dr Tom Russ, director of the Alzheimer Scotland Dementia Research Centre, said: “The results of the donanemab trial are very welcome and will bring many people with dementia and their families some much-needed hope.

“The top line results do not give much detail and the publication of the full results in the summer will be very helpful.

“While this is another encouraging development, the UK NHS is not ready to implement an infusion-based therapy such as donanemab or lecanemab, should they become licensed treatments in the UK.

“There needs to be significant support for struggling dementia assessment services which are still emerging from the Covid-19 pandemic to continue to diagnose, treat, and support people currently presenting while developing new ways to implement the disease-modifying treatments of the (near) future.”

The study also enrolled a smaller number of people (552) with high levels of tau, representing later stages of the disease.

When this group was combined with the intermediate tau group, donanemab also demonstrated “meaningful positive results”, Eli Lilly said, with a 29% slowing of decline on the commonly used Clinical Dementia Rating Scale Sum of Boxes.