Why UK Health Regulator is Rejecting Lecanemab Under NHS

Lecanemab (sold under the brand name Leqembi) is currently making headlines in Alzheimer’s news as the first disease-modifying medication with market approval for the treatment of Alzheimer’s disease in the United Kingdom. However, despite this novelty and approval, lecanemab has not been recommended for use by the National Health Service (NHS).

Why has this Alzheimer’s drug been rejected for prescribing to patients under the NHS? Here, we will explore the different factors driving this decision through an overview of the UK drug review and approval process.

What is lecanemab?

Lecanemab is a disease-modifying drug (i.e., it can slow down or stop a disease) that has been specifically developed to target the underlying causes of Alzheimer's disease instead of just targeting its symptoms.

This Alzheimer’s drug is an antibody. Antibodies are already being designed to treat other diseases, such as cancer. They are proteins that are naturally produced by the body’s immune system to fight diseases.

Lecanemab works by tagging amyloid plaques — clumps that build up in the brain, interfering with how the brain should normally work, causing Alzheimer’s disease. This tagging sends signals to the body’s immune system to come in and clear the plaques, thereby slowing down the progression of Alzheimer’s.

Clinical trial outcomes of lecanemab

This novel Alzheimer’s drug is given twice a month through a 10 mg/kg intravenous infusion, and it has shown promising results in clinical trials. A 2022 clinical trial publication consisting of 1,795 people showed that lecanemab reduced amyloid markers in early Alzheimer's disease, resulting in a 27% reduction in cognitive decline and improved function compared to placebo over 18 months.

In 2022, another clinical trial of 856 patients reports that lecanemab showed significant reductions in amyloid plaques and a slowing of cognitive decline.

Despite these positive treatment outcomes, there are side effects associated with lecanemab. From the clinical trials, some of these side effects included the following:

• Headache
• Seizures
• Confusion
• Dizziness
• Infusion-related reactions

Why did the UK health regulator reject lecanemab under NHS?

The Medicines and Healthcare Products Regulatory Agency (MHRA) and National Institute for Health and Care Excellence (NICE) are key regulatory bodies in the UK healthcare system, but they have different roles and areas of focus in decision-making processes.

The MHRA is the UK’s drug regulator, and it assesses the safety, efficacy, and quality of treatments. Their main area of focus is whether a treatment works as intended (its efficacy) and whether it is safe for use. It grants authorization for drugs to be used by the public.

NICE is the UK’s health regulator, and it guides the use of treatments within the NHS. Their main area of focus is on whether a treatment not only works but also provides good value for money. They make decisions based on budget impact and whether the NHS can afford the treatment (this is an economic evaluation).

On August 22, 2024, the MHRA granted a product license for lecanemab to be used in the early stages of Alzheimer’s disease after they reviewed the benefits and risks associated with it. However, NICE has not recommended it for use on the NHS. This means that lecanemab can only be prescribed privately.

Concerns about clinical trial results

While lecanemab has shown positive results by reducing amyloid plaques and slowing down cognitive decline, it is argued that the benefits of reduction in cognitive decline are too small to justify the costs.

In addition to the modest effects of lecanemab, there are concerns about the safety of lecanemab. Aside from the side effects of infusion-related reactions and headaches, the clinical trials have limited data about the long-term effects.

Cost-effectiveness considerations and budget impact on the NHS

NICE considers the budget impact of treatments on the NHS and whether the NHS can afford a new treatment.

NICE may have rejected lecanemab to be prescribed under the NHS based on this reason: lecanemab is expensive and the benefits do not quite outweigh the cost. It is already licensed in the United States, and it costs $26,000 per patient per year. According to a briefing paper released by NHS England, it is predicted that between 50,000 and 280,000 patients might be eligible for new treatments for Alzheimer’s disease if NICE recommends their use on the NHS.

The cost of implementing these drugs is predicted to be between £500 million and £1 billion per year; 50–60% of this total estimated cost is attributed to the drug, and the remaining costs are associated with patient assessment, diagnosis, and treatment administration.

Comparison of lecanemab and other Alzheimer’s medications

Though there are medications used to help manage the symptoms, there is currently no cure for Alzheimer's disease. However, this is an exciting time in research, marked by the emergence of new outcomes from clinical trials.

Currently, there are 127 drugs for Alzheimer’s disease in clinical trials; three of these have proven to be promising — donanemab, remternetug, and blarcamesine).

How do current medications compare to lecanemab?

Some Alzheimer's disease medications are currently approved for prescription under the NHS. However, they only treat some of the symptoms of Alzheimer's disease; they do not address its underlying cause. A comparison of these medications to lacenemab is shown below.

Future prospects for lecanemab

There is an open-label extension (OLE) study currently ongoing for lecanemab. This is a phase of study that takes place after the phase three part of the clinical trial is completed for a treatment that has potential benefits. This OLE study for lecanemab can provide additional data (particularly safety data) that can be submitted to address NICE’s concerns and to re-inform their decision.

The MHRA’s approval for lecanemab means the other treatments mentioned could be the next step in the long journey to finding treatments for Alzheimer’s disease. This is an exciting time in Alzheimer’s disease research, and research never stops. It must continue to drive novel innovations and landmark approvals.

Could a new treatment for Alzheimer’s disease become available on the NHS?

With the MHRA’s approval of lecanemab for use in the early stages of Alzheimer’s disease, it shows this novel treatment has some benefits. However, NICE has decided not to recommend it for use on the NHS at this stage as the cost outweighs the benefits. Currently, the committee's decision is still under consideration and may be updated in the future.

There are over 100 other treatments currently in clinical trials (three of which are showing promising results). The approval of the first disease-modifying Alzheimer’s medication, (lecanemab) marks a huge step in the journey.