Leqembi's UK Rollercoaster: A Yes From MHRA, A No From NICE

Eisai/Biogen’s Leqembi (lecanemab) has become the first drug for slowing the progression Alzheimer’s disease to win approval in Great Britain, but its availability on the National Health Service in England hangs in the balance as its reimbursement has been provisionally denied.

The UK regulator, the MHRA, approved the drug for early Alzheimer’s disease on 22 August, the same day that the health technology assessment institute, NICE, published draft guidance saying that the benefits of Leqembi were “too small to justify the costs.”

Leqembi provides on average four to six months’ slowing in the rate of progression from mild to moderate Alzheimer's disease, “but this is just not enough benefit to justify the additional cost to the NHS,” NICE said.

“The costs of providing the treatment, including fortnightly infusions in hospital and intensive monitoring for side effects, combined with the relatively small benefits it provides to patients means it cannot be considered good value for the taxpayer.”

NICE’s draft guidance is now out for public consultation until 20 September, after which the institute will convene a second appraisal committee meeting and produce its final recommendations.

Eisai and NHS England have also been asked to provide NICE with additional information to address its uncertainties.

The company, which welcomed the MHRA’s approval, said it remained “committed to working with NICE to make lecanemab available to eligible patients via the NHS as soon as possible.

“Eisai is unable to comment further on the NICE reimbursement process at this time,” a spokesperson for the company told the Pink Sheet.

Eisai was also unable to comment on the potential price of the drug for use in the NHS in Great Britain.

In the US, where Leqembi was approved in January 2023, the list price is around $26,500 per year.

Around 70,000 adults in England will be eligible for treatment with Leqembi if its reimbursement is approved by NICE.

Eisai is also endeavoring to secure NHS funding for Leqembi in Scotland, and is working with NICE’s Scottish counterpart, the SMC.

Approvals In UK & Elsewhere

As well as being licensed in the US and the UK, Leqembi is approved in Japan, China, South Korea, Hong Kong, Israel and the United Arab Emirates (it is currently marketed in the US, Japan and China).

The drug has “full coverage from Medicare [in the US] and in Japan it is included on the National Health Insurance Drug Price List,” Eisai’s spokesperson said, adding that “the applicable market access procedures are in process or planned in other markets where lecanemab is licensed.”  (Also see "Medicare Spending Forecast For Leqembi Reflects CMS Angst About Alzheimer’s Drug Costs" - Pink Sheet, 15 Apr, 2024.)

Securing EU marketing approval, by contrast, is proving challenging for Eisai and Biogen. The European Medicines Agency recommended against Leqembi’s approval last month – a decision that Eisai is currently contesting (see sidebar).

The EMA said that the benefits of the drug were not large enough to outweigh the risks associated with it – in particular the frequent occurrence of amyloid-related imaging abnormalities (ARIA), involving swelling and potential bleedings in the brain.

The MHRA also made note of the ARIA events when it licensed Leqembi for the treatment of mild cognitive impairment and mild dementia due to Alzheimer’s disease in adult patients.

It approved the drug for patients who have one or no copies of the apolipoprotein E4 gene (ApoE4), because it had been shown that the risk of symptomatic, serious radiographic imaging and recurrent ARIA events were higher in ApoE4 homozygous patients (ie, those with two copies of the ApoE4 gene) than in those with one or no copies of the gene.

"As with all medical products, we will keep its safety under close review, and with a controlled post-authorization safety study to be undertaken, we will ensure that the benefit risk of lecanemab in clinical use is closely followed up," the MHRA said.

Eisai has also submitted marketing authorization applications for Leqembi in other countries.

Too Expensive For NICE

NICE said that after examining the available research trial evidence, real-world data, and evidence from patient representatives and their carers, its independent appraisal committee recommended against funding Leqembi because it was “not a cost effective use of limited NHS funding.”

NICE chief executive Samantha Roberts said: “This is a new and emerging field of medicine which will no doubt develop rapidly. However, the reality is that the benefits this first treatment provides are just too small to justify the significant cost to the NHS. It is an intensive treatment to give to patients involving a hospital visit every two weeks with skilled staff needed to monitor them for signs of serious side effects, plus the cost of purchasing the drug.”

NICE also said that because the clinical trial of Leqembi “only reported outcomes when people had been taking lecanemab for 18 months there is a lack of evidence on its long-term effects.”

The institute noted that Leqembi and other similar treatments for Alzheimer’s disease that are “now coming on stream have prompted a great deal of debate about the prospects of being able for the first time to slow the effects of a condition that is progressive, life-limiting, complex and distressing.”

“For NICE to be able to approve a medicine for use in the NHS it must not only provide benefits to patients, but it must also represent a good use of NHS resources and taxpayers’ money,” it said.

The charity, Alzheimer’s Research UK, described news of the MHRA approval and the NICE recommendation as “bittersweet.”

“It’s a remarkable achievement that science is now delivering licensed treatments that can slow down the devastating effects of Alzheimer’s, rather than just alleviating its symptoms. However, it’s clear our health system isn’t ready to embrace this new wave of Alzheimer’s drugs,” the charity said.

“ For the foreseeable future, [Leqembi] will only be available to those who can afford its steep price tag in the private sector – which will be prohibitive for many,” it added.

Eisai serves as the lead for Leqembi’s development and regulatory submissions globally, with Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority. In Great Britain, Eisai and Biogen will co-promote the medicine, with Eisai distributing the product as the marketing authorization holder.