There was frustration in some corners of the media when it was announced that a new drug to slow the progression of Alzheimer’s was not going to be made available on the NHS.
Alzheimer’s wonder drug blocked on NHS over cost, a Telegraph headline ran. The Daily Mail went with: Alzheimer’s ‘wonder’ drug will be blocked by NHS from TODAY due to cost.
In late August, the UK’s National Institute for Health and Care Excellence (Nice), which provides clinical guidance for the NHS, rejected another Alzheimer’s treatment called lecanemab. The media response at that time was similar.
One million people in the UK have dementia, and this figure is expected to rise to 1.4 million by 2040. We have no drugs that slow the disease progression – so-called “disease-modifying drugs” – for this mind-robbing disease, only drugs to treat symptoms. It is clear that we need new drugs, so has Nice made the wrong decision?
Let’s dig a bit more into the rationale for Nice’s decision.
The “wonder” drug (or “miracle drug”) that some newspapers referred to is donanemab, an antibody that latches onto amyloid plaques in the brain and removes them. These plaques are the hallmarks of Alzheimer’s, but it is not known if they are the cause of Alzheimer’s or a consequence of it. (Some people have an abundance of these plaques but no Alzheimer’s.)
At the end of October, Nice declined to approve this drug for use on the NHS for treating early-stage Alzheimer’s disease. This was despite the UK’s drugs regulator, the Medicines and Healthcare Regulatory Authority (MHRA) approving donanemab.
How can we explain the different decisions of the two public bodies? And which one was right?
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. It aims to assess whether the benefits outweigh the risks. If they do, then the drug is approved for use in the UK.
Nice focuses on developing guidelines to support the adoption of new treatments, while considering value for money for the taxpayer alongside safety and effectiveness.
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 thought that about 70,000 people in the UK would be eligible for treatment with donanemab.
These drugs, donanemab and lecanemab, are given by infusion every two or four weeks and there are additional costs related to this and the monitoring needed.
To successfully treat patients in the very early stages of Alzheimer’s, these people first need to be identified. So new specialist diagnostic clinics would need to be created to test and confirm potential underlying disease. This might include genetic tests and lumbar puncture tests (to look for elevated amyloid in spinal fluid).
The drug infusions need to be started in specialist clinics with trained staff and facilities available for routine administration. This will all potentially increase the medication management burden on the patient and any family carer, which already can be difficult.
Nice concluded that donanemab slows the rate of decline in symptoms, but is not a cure. We don’t know enough about the long-term effects or the cost-effectiveness of this treatment. Nice consulted various expert groups on how well donanemab works, and the consensus was that it is modest at best.
The main outcome measurement 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 meaningful change is considered to be five points for people with Alzheimer’s who have mild cognitive impairment and nine points for people with Alzheimer’s who have mild dementia.
The change in the scale from the start of the trial to 76 weeks was −10.19 in patients receiving donanemab compared with −13.11 in patients receiving a placebo. This difference of 2.92 is less than what is considered to be a meaningful change for patients. Given this, donanemab is certainly not a “wonder” drug or a “miracle” drug, and describing it as such may give false hope to vulnerable people with dementia and their family carers.
Substantial side-effects
The side-effect burden of donanemab is substantial and like all new drugs, more side-effects may be identified when it is used in day-to-day practice. One particular concern is swelling and bleeding on the brain.
In human trials, brain swelling and bleeds occurred in 37% of patients on donanemab compared with 15% on the placebo. Overall, 13% of patients on donanemab stopped treatment because of the side-effects compared with 4% on placebo. Although the consequences are generally mild, it can lead to serious problems, such as seizures.
Hypersensitivity reactions, including swelling of the lips, face, tongue, throat and other parts of the body and breathing difficulties, are also a risk.
Many families in the UK have been touched by Alzheimer’s and fully understand the need for effective care. For families, one clear need is social care and support. Government after government has identified the need to invest in and reform social care. This, rather than spending money on drugs of questionable benefit, needs to be the priority.
Ian Maidment does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
This article was originally published on The Conversation. Read the original article.
