October 23, 2024

expert reaction to MHRA and NICE news on donanemab for Alzheimer’s disease

Scientists comment on MHRA saying ‘Donanemab licensed for treatment of Alzheimer’s disease in some adults’, and NICE draft guidance saying ‘Donanemab does not currently demonstrate value for the NHS’.

Prof Andrew Doig, Professor of Biochemistry, University of Manchester, said

“Donanemab is a new drug for Alzheimer’s Disease (AD) which tackles the build-up of a form of amyloid-β in the brain, the likely root cause of AD. It is an antibody that is administered through a needle inserted into a vein. Donanemab was tested with a clinical trial on about 2000 people with early-stage AD, run over 18 months.

“Donanemab shows real benefit to patients with mild AD by slowing down cognitive decline. The benefits are small, however, and there are concerns with the drug. Firstly, donanemab is not a cure for AD and it does not reverse, or even halt, the disease. All it does is to slow down the rate at which the disease progresses, as measured by loss of memory and other cognitive skills. In effect, patients who take donanemab see a delay to their loss of brain function by around six months. Secondly, carrying out a diagnosis to see who is eligible to take donanemab can only be carried out by a PET scan, similar an MRI scan, or by analysing cerebrospinal fluid, carried out by a lumbar puncture. These diagnosis methods are expensive and can be unpleasant for patients, so are not routinely available. Genetic tests to check that a patient is eligible for the drug are also useful. Thirdly, there is a small, but real risk, that donanemab can cause swelling or bleeding in the brain. About a quarter of patients in the trial showed evidence of this. Finally, the cost of the drug is very high, as is the cost of administering the drugs, as it requires regular MRI scans. Given the small benefits and high costs of the drug, NICE has not approved donanemab. NHS resources are limited (e.g. MRI machines) and are better spent elsewhere.

“This decision will be disappointing for patients and carers who are living with the burden of this horrible disease that has no cure. Nevertheless, there is hope. Better diagnostic methods are in development, such as a simple blood test, which would mean that PET scans or lumbar punctures are not needed. Donanemab has not been ruled out forever and this decision could change. We will continue to track how well it works over longer time periods. Costs may also come down. In addition, many other AD therapies, such as other antibodies are on the way. Some of them are likely to work better than donanemab and could be approved.

“Donanemab and other related drugs have shown that it is possible to slow cognitive decline caused by AD. They therefore point the way to a future where AD can be treated, bringing benefit to millions of people.”

Prof B. Paul Morgan, UK Dementia Research Institute Cardiff, Cardiff University, said:

“NICE has reached the decision that the Alzheimer’s drug Donanemab, despite having a modest effect on rate of disease progression, does not clear the clinical benefit and cost-effectiveness hurdles for approval for use in the NHS.  The drug requires monthly infusions and carries significant risk of side effects, necessitating very close monitoring using imaging and other expensive tests.

“The decision is not surprising in that it closely mirrors that made for another Alzheimer’s drug, Lecanemab, in August.  Both drugs are monoclonal antibodies that target amyloid, the main component of the plaques that develop in the brain in Alzheimer’s disease. They differ subtly in that Lecanemab targets the soluble form of amyloid to prevent plaque formation while Donanemab targets amyloid aggregates in plaques. Nevertheless, both efficiently clear amyloid and have a similar slowing effect on progression of cognitive decline in patients. Both also share the same risks, notably an increase in inflammation in brain blood vessels that can lead to bleeding in the brain. 

“The decision will be a disappointment to Alzheimer’s sufferers and their carers. It means that there are no disease-modifying drugs for Alzheimer’s currently approved in the UK. The decision also highlights the problems with the amyloid-targeting drugs – eye-wateringly expensive, difficult to administer and potentially harmful. Balancing these against a modest impact on the disease, the decision made by NICE is understandable.  These drugs are already in use in the US and elsewhere, albeit at lower than predicted uptake, and more will be learned from their wider use.  In particular, improvements in patient selection and monitoring may tip the balance in the future.

“The final lesson from these disappointments is that we need better drugs for Alzheimer’s disease, moving beyond the focus on amyloid clearance and targeting other aspects of the disease that may provide better, safer and affordable routes to effective therapy of this awful disease.”

Prof Rob Howard, Professor of Old Age Psychiatry, University College London (UCL), said:

“NICE have made the correct and responsible decision that donanemab treatment within the NHS cannot be considered to represent a cost-effective use of resources. Importantly, the estimated potential value-based benefits of donanemab to patients with dementia and their families were between only a fifth and a sixth of the actual costs of buying and administering the treatment.

“Although there is considerable uncertainty about both the meaningfulness of the very small benefits seen with treatment and any longer term effects beyond the 18 months of data collected in the pivotal trials, NHS access to these new drugs would not have made an appreciable difference to the experience of patients and families affected by dementia. 

We have well-established drug treatments and psychosocial interventions for Alzheimer’s disease that are already available to people with dementia within the NHS but are not universally accessed. Our priority now should be to ensure that everyone with dementia who might benefit from these cost-effective interventions and adequately resourced adult social care services is able to access them. It would be unhelpful if the conversation about how we adequately fund NHS and social care for people with dementia was distracted by the issue of these new drugs. We should thank NICE for their leadership and clarity in this regard.”

Prof Siddharthan Chandran, Director of the UK Dementia Research Institute, said: 

“These first drugs are just the opening chapter for Alzheimer’s treatments. Today’s MHRA approval of donanemab is another step towards a future where we can begin to offer treatments to people affected by dementia. In this case, NICE’s initial recommendation is that the benefits of the drug are not significant enough to make it cost effective, which means it will not be available to patients on the NHS. This will be disappointing to many. However, I do believe we are at a pivotal moment in our research mission to develop better, safer treatments.

“This is a long journey and is only possible because of long-term investment in research that underpins the identification and development of new treatments. The MRC-funded UK Dementia Research Institute is at the forefront of research into dementias, and working together with our many partners from patient charities, leading UK universities, the NHS and industry we are hopeful that major advances in diagnostics and treatments are ahead of us.”

Prof Charles Marshall, Clinical Senior Lecturer and Honorary Consultant Neurologist, Queen Mary University of London (QMUL), said:

“This will be very disappointing news for people affected by Alzheimer’s who are desperate for something that can slow the course of the disease. Hopefully, future developments will allow the introduction of treatments like this in the NHS. For this we will need investment in modernised dementia clinics that can deliver diagnosis and treatment appropriately, as well as evidence that Donanemab continues to slow Alzheimer’s disease over a longer time period, which could make it cost effective. We need NHS patients to be involved in generating this evidence so that we can see how effective Donanemab might be if used widely in the UK.”

Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and President of the British Neuroscience Association said:

“While people living with dementia and their loved ones will undoubtedly be disappointed by the decision not to fund this new treatment on the NHS, the good news that new treatments can slow disease even a small amount is hopeful.  New research is bringing us closer to treatments that should be safer and more effective. This decision on the amyloid targeting drug donanemab is not a surprise as it is consistent with the recent recommendations for lecanemab, a very similar drug.  Donanemab is an antibody that removes amyloid pathology from the brain. This is not a cure. The treatment slows disease progression modestly but does not stop or reverse symptoms.  The treatment also comes with potentially serious side effects of brain swelling and brain bleeding.”

Prof Tom Dening, Professor of Dementia Research, School of Medicine, University of Nottingham, said:

“Given the MHRA and NICE positions previously stated on lecanemab, these decisions in relation to donanemab are hardly surprising. My personal position stands more with NICE, because I think that we don’t do enough to support people with dementia after they get a diagnosis, and the expensive monoclonal antibodies are a bit of a distraction from the main issue, which is to help people live the best lives they can with the diagnosis.”

Professor Fiona Carragher, Chief Policy and Research Officer at Alzheimer’s Society, said:  

“Disease-modifying therapies like donanemab and lecanemab offer a new horizon of hope in the fight against dementia. MHRA’s approval of donanemab marks another milestone in this journey, but it comes alongside a draft NICE decision not to recommend donanemab for use on the NHS. While this is disheartening, we respect the decision of the regulator. 

“In other diseases like cancer, treatments have become more effective, safer and cheaper over time and we hope to see similar progress in dementia. 

“With around 20 Alzheimer’s disease drugs in late-stage clinical trials, more drugs will be submitted for approval within the next few years. 

“New treatments are an important catalyst for change, but they are only one piece of the puzzle. While preparing for the future, we must not lose sight of the million people living with dementia in the UK today – a third of whom don’t have a diagnosis. 

“We need to see significant government investment to bring about radical change so that everyone with dementia in the UK can get an early and accurate diagnosis. Without this, people won’t be able to access existing treatments and interventions to help manage their symptoms today or be ready for the disease slowing treatments of tomorrow.” 

Hilary Evans-Newton, Chief Executive at Alzheimer’s Research UK, said:

“Today’s announcement marks another frustrating setback for people affected by Alzheimer’s disease. We finally have two new treatments licensed in Britain for Alzheimer’s, but it’s incredibly disappointing that NHS patients in England and Wales won’t receive them. While these drugs are not cures and come with risk of side effects, trials show they are the first treatments to slow the decline in memory and thinking skills linked to Alzheimer’s, rather than just alleviating symptoms.

“NICE’s recent interim decisions on lecanemab and donanemab highlight uncertainty about their benefits compared to the significant costs of delivering them in the NHS. Yet dementia remains the UK’s leading cause of death, and without action, an ageing population means more families will be affected, driving up NHS costs through emergency admissions and care.

“NHS England has identified nearly 30 other dementia treatments that could be available by 2030, giving the government and NHS a crucial opportunity to transform how dementia is treated – just as Labour pledged in their manifesto. But we still haven’t heard from Health Secretary Wes Streeting on how he plans to break the deadlock we’re facing, where research is delivering new treatments but they remain out of reach for NHS patients. We’ve written to the Health Secretary again, calling for his leadership to bring together NICE, NHS England and industry so that people with dementia in the UK aren’t left behind.

“Today’s decision also risks signalling that the UK is no longer a good place to launch new dementia treatments. Although the UK has a strong history in dementia research, it currently hosts just 7% of global dementia trials and under 3% of participants in phase 3 trials for dementia worldwide live here. How the government tackles these challenges will show if they’re serious about bringing innovation to the NHS and cutting the red tape that is limiting people’s access to research and innovative medicines.”

MHRA decision and NICE draft guidance on donanemab for Alzheimer’s disease was published at 10:00am UK time Wednesday 22^nd October 2024. 

https://www.nice.org.uk/guidance/indevelopment/gid-ta11221

Declared interests

Prof Andrew Doig: Andrew Doig is a Professor of Biochemistry at the University of Manchester. He is a founder and director of PharmaKure, a spin-out company working on diagnostics and drugs for Alzheimer’s Disease and other neurodegenerative conditions.

Prof Rob Howard: I don’t have any relevant CoIs.

Prof Charles Marshall: I have no relevant conflicts to declare.

Prof Siddharthan Chandran: Siddharthan is the academic lead of Neurii, a £5M partnership to deliver patient focused digital health solutions for dementia, part funded by Eisai. The UK Dementia Research Institute holds partnerships with charities (BHF, Alzheimer’s Research UK, Alzheimer’s Society and LifeArc), and industry (Lilly, Eisai, Astex, SPARC and Ono).

Hilary Evans-Newton No COI.

Prof Tom Dening: No COI.

Professor Fiona Carragher: No conflicts of interest.

Prof Tara Spires-Jones: I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.

For all other experts, no reply to our request for DOIs was received.