UK regulator the National Institute for Health and Care Excellence (NICE) has ruled against the use of a second monoclonal antibody for Alzheimer’s disease, just two months after rejecting Eisai’s lecanemab (Leqembi). 

NICE concluded that Eli Lilly’s donanemab (Kisunla) only provides a “small benefit” to patients and “more evidence is needed on its clinical and cost-effectiveness”, despite its approval by the UK Medicines and Healthcare products Regulatory Agency (MHRA). 

According to the MHRA approval, eligible patients are limited to apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers, which is a requirement for the class of currently approved amyloid-targeting therapies in Great Britain.  

The clinical trial evidence presented suggests that the monthly injection can slow Alzheimer’s disease progression by four to seven months, NICE’s independent committee heard. 

However, the committee felt there are significant uncertainties about how much benefit donanemab provides, and how long this lasts for after stopping treatment. 

The committee also heard that clinical trial evidence suggests there are significant health risks associated with the treatment. A third of donanemab recipients experienced amyloid-related imaging abnormalities (ARIA) caused by brain swelling and bleeding. 

Helen Knight, Director of Medicines Evaluation at NICE, said: “Our independent committee looked at all the available evidence, including the benefits for carers. This shows donanemab could slow down cognitive decline by four to seven months, but this is just not enough benefit to justify the additional cost to the NHS. The cost-effectiveness estimate for donanemab is five to six times above what NICE normally considers an acceptable use of NHS resources. 

“I know this will be disappointing news, but this is an emerging field of medicine and there are other treatments being developed.” 

The consultation on the draft NICE guidance on donanemab will close on 20 November 2024. 

Further evidence on both drugs needed 

Despite the guidance, there is hope that with further evidence, both Alzheimer’s drugs will be made available on the NHS in the future.  

Philippa Salter, Managing Neurology Analyst at GlobalData, commented: “Although Leqembi and Kisunla represent a major breakthrough in the AD market as the first disease-modifying therapies (DMTs), their efficacy is modest. NICE had requested further evidence regarding the magnitude and benefit of the effects of the drugs and what the overall costs would be. This is particularly important to understand for Kisunla, as this drug is not designed to be taken indefinitely, which means that its total lifetime cost of therapy could be significantly cheaper than Leqembi. 

“Further real-world evidence… and clinical trial data will be vital for the success of both drugs. GlobalData forecasts that in the 8MM (US, France, Germany, Italy, Spain, UK, Japan, and China) Leqembi and Kisunla could generate sales of approximately $3.5 billion and $2 billion in 2030, respectively.”