New Alzheimer's drug receives positive feedback from European Medicines Agency after initial refusal

It was just a few months ago that the committee for medicinal products for human use (CHMP) and the European Medicines Agency (EMA) declined the marketing authorisation for donanemad - a drug developed by pharmaceutical company Eli Lilly to treat early-stage Alzheimer's disease. Their decision at the time was based on the disproportionate benefits compared to the "potentially" life-threatening risks.

However, last week, the EMA issued a positive feedback recommending its use for the treatment of this disease in adults with confirmed amyloid pathology who are heterozygous or non-heterozygous carriers of the ApoE4 protein.

The pharmaceutical company has announced that the European Commission is expected to take a final regulatory decision on the marketing authorisation of this drug, distributed under the name Kisunla, in the EU in the coming months.

"This positive feedback is an important milestone in our work to get donanemab to the right patients across Europe," said Patrik Jonsson, executive vice president and president of Lilly International. "Donanemab can make a significant difference in the lives of people with early symptomatic Alzheimer's disease and Lilly remains committed to advancing through ongoing clinical trials."

Alzheimer's disease currently affects 6.9 million people in Europe and this number is expected to almost double by 2050 due to the increasing ageing of the population. Approximately one third of people with mild cognitive impairment or mild dementia due to Alzheimer's disease progress to the next clinical stage of the disease within a year.

"This data gives us an idea of the magnitude of a disease with both health and social consequences, given the extreme dependence of patients in advanced stages," said medical director of Lilly Spain José Antonio Sacristán.

He added that the approval of key institutions allows them to "think about changing the course of the disease in its early stages". "To do this, it is essential to enhance early diagnosis, access to biomarkers and the training of multidisciplinary teams in our healthcare system," he said.

The CHMP and EMA based the new direction mostly on the TRAILBLAZER-ALZ 2 clinical trial, which demonstrate that donanemab significantly slows cognitive and functional decline and reduces the risk of progression to the next clinical stage of the disease, as well as data from the TRAILBLAZER-ALZ 6 clinical trial, which evaluated an adjustment in the dosing regimen.

In the TRAILBLAZER-ALZ 6 study, adjustment of the dosing regimen significantly reduced the incidence of amyloid-related imaging abnormalities with oedema/effusion (ARIA-E) compared to the original TRAILBLAZER-ALZ 2 regimen at 24 and 52 weeks, achieving similar levels of amyloid plaque clearance and P-tau reduction217.

Amyloid-imaging abnormalities (ARIA) with oedema/effusion (ARIA-E) and haemorrhage/hemosiderosis (ARIA-H) are side effects of this class of drugs that usually do not cause symptoms, but can be serious and life-threatening. Carriers of one or two copies of the ApoE4 gene may have an increased risk of developing Alzheimer's disease and experiencing ARIA. Patients should discuss any safety concerns with their doctor.

Donanemab is administered by infusion once a month. It is currently marketed in the US and other countries including Japan, China, UK, UAE, Qatar, Kuwait, Bahrain, Singapore, Taiwan, Brazil, Mexico and Australia. In the US, Japan, China and other countries, donanemab is approved for patients regardless of ApoE4 gene status.

It is the first treatment targeting amyloid plaques with evidence to support discontinuation of treatment once the plaques have been cleared, which could mean lower treatment costs and fewer infusions.