Donanemab for the treatment of Alzheimer's disease is not a 'miracle cure' – not making it available on the NHS is the right choice

There was disappointment in some parts of the media when it was announced that a new drug to slow the progression of Alzheimer's disease would not be available on the NHS.

A headline in the Telegraph read: “Alzheimer's miracle cure blocked by NHS over cost.” The Daily Mail said: The 'miracle cure' for Alzheimer's is blocked by the NHS from TODAY over cost.

In late August, Britain's National Institute for Health and Care Excellence (Nice), which provides clinical guidance to the NHS, rejected another Alzheimer's treatment called lecanemab. The media response at the time was similar.

One million people in the UK suffer from dementia and this number is expected to rise to 1.4 million by 2040. We don't have drugs that slow the progression of the disease – so-called “disease modifying drugs” – only drugs to treat symptoms for this mind-numbing disease. It is clear that we need new drugs. So did Nice make the wrong decision?

Let's look a little more closely at the reasons behind the Nice decision.

The “miracle drug” (or “miracle cure”) that some newspapers have been referring to is donanemab, an antibody that attaches to and removes amyloid plaques in the brain. These plaques are the hallmarks of Alzheimer's disease, but it is not known whether they are the cause or a consequence. (Some people have lots of these plaques but don't have Alzheimer's disease.)

At the end of October, Nice refused to approve this drug for use on the NHS to treat early-stage Alzheimer's disease. This happened despite the UK's medicines regulator, the Medicines and Healthcare Regulatory Authority (MHRA), having approved donanemab.

How can the different decisions of the two public bodies be explained? And which one was correct?

We can understand the decisions in the context of the different roles of the MHRA and Nice. Essentially, the MHRA reviews the scientific evidence and decides whether the drug is safe and effective. The aim is to assess whether the benefits outweigh the risks. If this is the case, the drug is approved for use in the UK.

Nice focuses on developing guidelines to support the introduction of new treatments, taking into account safety and effectiveness as well as value for money for the taxpayer.

We don't know how much donanemab will cost in the UK. In the US the list price is £25,000 per patient per year. It is estimated that around 70,000 people in the UK would be eligible for treatment with donanemab.

These drugs, donanemab and lecanemab, are given as an infusion every two to four weeks and incur additional costs for this and the necessary monitoring.

In order to successfully treat patients in the very early stages of Alzheimer's disease, these individuals must first be identified. Therefore, new specialized diagnostic clinics would have to be created to test and confirm possible underlying diseases. These may include genetic testing and lumbar puncture testing (to look for increased amyloid in the spinal fluid).

Drug infusions must be started in specialized clinics with trained staff and facilities for routine administration. All of this will potentially increase the burden of medication management on the patient and their caregivers, which can already be difficult.

Nice concluded that donanemab slows the resolution of symptoms but is not a cure. We don't know enough about the long-term effects or cost-effectiveness of this treatment. Nice surveyed several groups of experts about how well donanemab works, and the consensus was that the effect was moderate at best.

The main outcome measure used in the clinical trial was the Integrated Alzheimer's Disease Rating Scale at 76 weeks. The scale, which measures both cognition and daily functioning, ranges from 0 to 144. A significant change is five points for people with Alzheimer's with mild cognitive impairment and nine points for people with Alzheimer's with mild dementia.

The change in scale from baseline to week 76 was -10.19 in patients who received donanemab compared to -13.11 in patients who received placebo. This difference of 2.92 is less than what is considered a meaningful change for patients. With this in mind, donanemab is certainly not a “miracle cure” or “miracle cure”, and labeling it as such could give false hope to vulnerable people with dementia and their carers.

Significant side effects

The side effect burden of donanemab is significant and, as with all new medications, more side effects may be experienced when used in daily practice. A particular problem is swelling and bleeding in the brain.

In human studies, 37% of patients receiving donanemab experienced brain swelling and bleeding compared to 15% receiving placebo. Overall, 13% of patients receiving donanemab discontinued treatment due to side effects, compared to 4% receiving placebo. Although the effects are generally mild, serious problems such as seizures can occur.

Hypersensitivity reactions, including swelling of the lips, face, tongue, throat, and other parts of the body, and difficulty breathing, are also a risk.

Many families in the UK are affected by Alzheimer's disease and fully understand the need for effective care. A clear need for families is social care and support. Government after government has recognized the need to invest in and reform social care. This must be a priority rather than spending money on drugs whose benefits are questionable.