NICE Rejects Alzheimer’s Drugs Over Limited Benefit for Cost

Two new drugs to treat Alzheimer’s disease have been rejected for NHS use in England and Wales because they are too expensive to justify their “relatively small” benefits. 

In final draft guidance, the National Institute for Health and Care Excellence (NICE) said it could not recommend donanemab (Kisunla, Eli Lilly) or lecanemab (Leqembi, Eisai) for adults with mild cognitive impairment (MCI) or mild dementia caused by Alzheimer’s disease.

The guidance applies to adults who are either heterozygous for the apolipoprotein E4 gene or who do not carry it.

The Alzheimer’s Society described the decision as “highly disappointing.”

Professor Fiona Carragher, chief policy and research officer at the charity, said “the science is flying but the system is failing.”

Modest Benefits at High Cost

Both drugs have been shown to slow cognitive decline. However, NICE concluded that the benefits were too small to justify the high costs to the NHS, including their administration.

The decision upholds NICE’s earlier position from March this year.

Tackle Underlying Disease

There are currently no pharmacologic treatments for MCI caused by Alzheimer’s disease.

Donanemab and lecanemab are monoclonal antibodies designed to reduce amyloid plaques in the brain. They aim to slow disease progression, unlike current treatments that only relieve symptoms. 

Donanemab is given monthly via IV infusion. Lecanemab is administered intravenously every 2 weeks.

Clinical Evidence Considered

Clinical evidence for donanemab came from the phase 3, randomised placebo-controlled double-blind TRAILBLAZER‑ALZ 2 trial, which included 1736 people aged 60-85 with early symptomatic Alzheimer’s disease (MCI or mild dementia).

Lecanemab was evaluated in the phase 3, randomised, placebo-controlled, superiority double-blind Clarity AD trial, involving 1795 people aged 50-90 with early Alzheimer’s disease. 

Both trials showed that patients on active treatment continued to experience worsening cognitive function over time, but at a slower rate than those on placebo. 

Donanemab may have some sustained benefit after treatment ends, but for lecanemab, long-term outcomes remain unclear, the regulator said.

Although both treatments delayed progression from mild to moderate Alzheimer’s by 4-6 months, NICE concluded that this did not justify the overall costs of purchasing and administering the drugs.

Impact on NHS Resources

Helen Knight, director of medicines evaluation at NICE, said that significant NHS resources would be needed to enable access to the drugs.

“While we recognise the hope these treatments offer, the evidence shows they only provide modest benefits at best,” she said.

Knight added that NICE remained focused on the promising pipeline of new Alzheimer’s drugs.

The regulator said it would consider revisiting guidance on lecanemab once data on a subcutaneous reformulation become available.

Hilary Evans-Newton, chief executive at Alzheimer’s Research UK, described the rejection as a “painful setback” for patients with Alzheimer’s but not surprising given the “modest benefits.”

Rob Howard, professor of old age psychiatry at University College London noted to the Science Media Centre that the annual cost of the drugs and the safety monitoring required “would have been close to the cost of a nurse’s salary for each treated patient.”

Charles Marshall, professor of clinical neurology at Queen Mary University of London, said more effective drugs are needed “so that the magnitude of benefit becomes indisputable.”

Evans-Newton noted that with more than 30 Alzheimer’s drugs currently in late-stage trials globally, “momentum is building.” However, the government needed to work with NICE, the NHS, and industry “to pilot licensed drugs, gather more data, and prepare the health system for what’s ahead,” she said.

Registered stakeholders, including the manufacturers and patient groups, have until 8 July to appeal against NICE’s final draft recommendations. 

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.