Developing donanemab – balancing cost versus benefit

A new regulatory authorisation has opened opportunity for eligible Alzheimer’s patients in Great Britain to access a new treatment that could provide them with “more time in the early symptomatic stage of the disease to do what matters most to them,” shared Ilya Yuffa, Executive Vice President And President of Lilly International, Eli Lilly and Company, following the Medicines and Healthcare products Regulatory Agency (MHRA)’s decision this week. The biologic treatment was granted approval as Kisunla™ (donanemab-azbt) in the US by the Food and Drug Administration (FDA) in July 2024.

Anti-amyloid beta (Aβ) monoclonal antibody (mAb) donanemab is part of new class of amyloid targeting therapies, and while it can slow Alzheimer’s disease progression by four to seven months, NICE’s independent committee highlighted, they were uncertain about making it available for NHS patients.

For example, with the “relatively small” benefit the treatment can provide, according to NICE, the UK public body deemed that donanemab is not currently “good value for the taxpayer” as a treatment offered on the NHS.

NICE’s committee emphasised other concerns around its cost-effectiveness, such as patients requiring regular monthly infusions.

“The cost-effectiveness estimate for donanemab is five to six times above what NICE normally considers an acceptable use of NHS resources,” explained Helen Knight, Director of medicines evaluation at NICE.

As such, NICE requested that Eli Lilly and NHS England provide further evidence that address the uncertainties.

Final recommendations on donanemab are expected following close of the consultation on the draft guidance on 20 November, NICE shared.

 Weighing up the benefits

 “This is the second time in 2024 that on the same day that the MHRA has approved a new disease-modifying therapy for [Alzheimer’s], the initial recommendation from NICE was to not cover the drug on the NHS,” commented Philippa Salter, Managing Neurology Analyst at GlobalData. “In August 2024, Eisai/Biogen’s anti-Aβ mAb Leqembi (lecanemab) became the first [disease-modifying therapy] to be approved for [Alzheimer’s] in the UK”.

“Leqembi and Kisunla represent a major breakthrough in the [Alzheimer’s] market as the first [disease-modifying therapies],” stated Salter.

Professor Paul Morgan, UK Dementia Research Institute Cardiff, Cardiff University, explained the differences between the two drugs: “Lecanemab targets the soluble form of amyloid to prevent plaque formation while donanemab targets amyloid aggregates in plaques. Nevertheless, both efficiently clear amyloid and have a similar slowing effect on progression of cognitive decline in patients”.

However, side effects of these drugs, such as “the development of amyloid-related imaging abnormalities (ARIAs), remains a significant concern”. With MRI scans being required before patients are given these drugs, this increases the overall treatment cost, Salter shared.

Yet, as donanemab is not meant to be given to patients permanently, acknowledged Salter, “the total lifetime cost of therapy could be significantly cheaper than Leqembi”.

She emphasised it is important to note that the current decision from NICE for both drugs are not final.

Future prospects of donanemab

Looking ahead at the therapeutic market, GlobalData predicts that “in the US, France, Germany, Italy, Spain, UK, Japan, and China, Leqembi and Kisunla could generate sales of approximately $3.5 billion and $2.0 billion in 2030, respectively.”

Professor Morgan proposed that Alzheimer’s drug development needs to move “beyond the focus on amyloid clearance and targeting other aspects of the disease that may provide better, safer and affordable routes to effective therapy.”

“With around 20 Alzheimer’s disease drugs in late-stage clinical trials, more drugs will be submitted for approval within the next few years,” declared Professor Fiona Carragher, Chief Policy and Research Officer at Alzheimer’s Society.