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The U.S. Food & Drug Administration (FDA) has today approved aducanumab (Aduhelm) to treat patients with Alzheimer’s disease.
Prof Richard Morris, Professor of Neuroscience, University of Edinburgh, said:
“I am relieved to see the approval of aducanumab by the FDA. Despite concerns about the extent to which this drug will help patients, it is great news that a start has finally been made in the search for treatments targeting the causes of Alzheimer’s Disease”.
Dr Joseph Butchart, of the University of Exeter Medical School, said:
“Alzheimer’s Disease is now the biggest killer in the UK, overtaking heart disease and cancer, and we desperately need new treatments. The approval of this experimental drug for use within the United States provides tremendous hope that more effective drugs are on the horizon. However, I think the regulatory authorities in the UK and Europe would need much stronger evidence for the effectiveness of aducanumab before it could be approved for clinical use in our patients with Alzheimer’s disease. More clinical research is urgently needed to properly test the safety and effectiveness of this drug and others that could really make a difference to people living with this terrible disease.”
Hilary Evans, Chief Executive at Alzheimer’s Research UK, said:
“Today’s decision by the FDA marks a pivotal moment in the search for life-changing new treatments for Alzheimer’s disease. The approval is a positive step forward for people with early Alzheimer’s disease in the US and we welcome the opportunity for Biogen to conduct a post-approval clinical trial to reveal more about the potential real-world benefits of aducanumab. Aducanumab will be the first ever drug to reach patients in the US that tackles the underlying disease process itself. The findings of these additional studies could pave the way for a new generation of life-changing drug treatments.
“People with dementia and their families have been waiting far too long for life-changing new treatments. It is now essential that regulatory authorities here assess the evidence to decide whether they believe the drug is safe and effective for use in the UK. Alzheimer’s Research UK has today written to the Health Secretary Matt Hancock calling on the government to prioritise and accelerate this process, to give people with Alzheimer’s the answers they need as quickly as possible.
“We hope this historic ruling has an immediate positive impact on the global search for effective dementia treatments. Aducanumab is only suitable for certain individuals with early Alzheimer’s, so renewed focus and investment in dementia research will speed up the search for life-changing treatments for those with other dementias, and in the later stages of disease.”
“Aducanumab is still some way from reaching patients in the UK, but Alzheimer’s Research UK continues to work tirelessly to prepare the UK health system so that any new drug can reach those who need it most without delay. Research has the potential to transform the lives of everyone affected by dementia and we will keep working to make more breakthroughs possible.”
Prof Tara Spires-Jones, UK Dementia Research Institute at The University of Edinburgh & Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:
“The approval of aducanumab to treat Alzheimer’s disease in the US is phenomenal news for researchers as it is the first approved drug that attacks disease pathology; however, the drug’s ability to slow memory decline is less convincing. This drug lowers the amount of amyloid plaques in the brain, which is hoped to slow disease progression if given to people in early stages of Alzheimer’s. This is very exciting for scientists trying to develop truly life changing treatments, but we still have a long way to go.”
Dr Elizabeth Coulthard, Consultant Senior Lecturer in Dementia Neurology at the University of Bristol, said:
“This is a significant milestone as it is the first drug that will be used in clinical practice anywhere in the world to slow progression of Alzheimer’s Disease. The benefit of the drug is modest, but unlike previously licensed drugs, it helps to slow the underlying cause of Alzheimer’s rather than just treat the symptoms of disease.
“We still do not know if it will be approved for use in the UK. If it is approved in the UK, it is likely to be licensed only for people with mild symptoms.
“There are huge implications for how we run services in the UK. At the moment, we diagnose Alzheimer’s Disease relatively late in the disease process – after people have established dementia. We know that Alzheimer’s disease accumulates for up to 2 decades before dementia is diagnosed. During this time people have no symptoms or only mild symptoms. To give treatments like aducanumab or similar drugs in the UK, we will need to diagnose Alzheimer’s Disease earlier when people have only mild symptoms.
“Aducanumab is controversial because it was tested in two trials and only worked in one of them. BIOGEN presented evidence that the difference between the two trials could be explained by more of the high dose was used in the successful trial, and there was a hint that the higher dose also worked in the unsuccessful trial. This was enough to convince the FDA. However there are still questions about how effective aducanumab will be in real-world clinical practice. As with most drugs, if this is licensed in the UK, we will need to carefully monitor patients who receive the drug to detect rare side-effects and understand benefits.”
Dr Ivan Koychev, Senior Clinical Researcher, University of Oxford and Clinician Scientist at Dementias Platforms UK (DPUK), said:
“This is a highly significant event for the field for Alzheimer’s disease as it is the first therapy targeting its presumed cause (build-up of amyloid proteins in the brain). It is also significant as the approval was heavily reliant on evidence of the treatment affecting amyloid plaques with only a modest effect on cognition. The news are significant for those with early stages of Alzheimer’s disease they are most likely to receive the drug. Today’s decision was contentious due to the complex nature of the studies conducted by the company, the fact that the trials were stopped early on account of lack of effectiveness, the strong advice against approval from FDA’s expert committee and the minimal effect on cognition. The roll-out of the treatment will rely on clinics being able to demonstrate these plaques either through PET head scans or lumbar punctures – if aducanabumab is approved in the UK, this will be a challenge for the mainstream NHS Memory Clinics. What comes next will be an assessment of the value for money for healthcare systems of this treatment, the development of capacity to deliver it if so as well as the start of data accumulation on the effectiveness of the drug on hard outcomes in Alzheimer’s disease (loss of cognitive and day-to-day abilities) as well as studies testing the effect of the drug in individuals in preclinical stages of the disease.
“In short, it is not licensed yet in the UK; the US will likely allow it for those in very early stages of Alzheimer’s disease but there were no details on that.”
Prof Craig Ritchie, Director of Brain Health Scotland and Professor of the Psychiatry of Ageing, University of Edinburgh, said:
“This is broadly anticipated – they have based their conclusion for accelerated approval on clearance of amyloid BUT need Phase IV testing to confirm clinical benefit. Therefore access to the drug in the USA will be through more research studies. This is good news for drug development as it shows that treating the biology of the disease is sufficient to get to Phase IV – so they have lowered the bar to Phase IV BUT this does not mean there will be wide access. This is the view that I think (personal opinion) that will be shared by EMA and MHRA. Usually Phase IV trials are paid for by the drug company running the study but are usually a lighter touch so more people can get recruited in a Phase IV trial from a real world setting. This has been closely watched because of the time since the last approval for a drug in this area and the prevalence of the disease. It is contentious because of the equivocal clinical data.
“Therefore the announcement by the FDA is welcomed as it opens a new chapter for drug treatments in Alzheimer’s disease. Use within the NHS though remains some months away and it is critically important that the safe use of this intervention in those people most likely to benefit is fully considered. We also need to ensure that we collect real world data on the benefits and side effects of the medication to help us to refine how to use this intervention well. It’s certainly a new chapter but by no means the end of the story.”
For further info and an FAQ on aducanumab, see here: https://www.brainhealth.scot/aducanumab
Prof Robert Howard, Professor of Old Age Psychiatry, UCL Division of Psychiatry, UCL, said:
“As a dementia clinician and researcher with personal family experience of Alzheimer’s disease, I want to see effective dementia treatments as much as anyone. I consider the approval of aducanumab represents a grave error that will have only negative impact on patients and their families and that could derail the ongoing search for meaningful dementia treatments for a decade.
“Amazingly, the FDA have sidestepped available clinical trial outcomes data that indicate the drug probably doesn’t work. Their Accelerated Approval Pathway facilitates the approval of potentially valuable therapies and the approval given today is based on the expectation “that reduction in amyloid plaque will result in reduction of clinical decline”. The FDA have ignored the data we already have from over 3,000 aducanumab trial participants treated for 18 months. These indicate there is no consistent efficacy signal in terms of slowing decline in cognition or function.
“FDA Approval closes the door on further placebo-controlled trials of aducanumab that might have helped to resolve disputes about efficacy quickly and cleanly. Now, we’ll wait a decade before it becomes obvious to everyone that there are no benefits – only high healthcare costs – associated with the treatment.”
Dr Richard Oakley, Head of Research at Alzheimer’s Society, said:
“It’s promising to see that aducanumab has been approved for use in people with early stage Alzheimer’s disease—the first drug to be approved in nearly twenty years by the US regulatory authorities. We await the opinion of the European Medicines Agency and the outcome of any application made to the UK regulatory authorities, to give clarity to people with early Alzheimer’s disease in the UK. Whatever the outcome of their decision, this is just the beginning of the road to new treatments for Alzheimer’s disease. As this drug will only benefit a proportion of people in the early stages of Alzheimer’s disease, there are hundreds of thousands more who may not be eligible, so we must keep searching for drugs for all stages of Alzheimer’s disease and for other types of dementia. We are proud to say that Alzheimer’s Society was part of a pivotal genetic discovery for the first Alzheimer’s gene in the 1990s, which paved the way for anti-amyloid drugs like the one announced by Biogen.
“Research will beat dementia. We have seen tremendous progress over the last decade, leading up to this decision today, but we need to maintain the momentum: the Government must honour their commitment to double dementia research funding. Dementia is the biggest killer in the UK, so we owe it to all 850,000 people living with dementia in the UK and their families to make a world without dementia a reality.”
Prof Paul Morgan, Director of the Systems Immunity Research Institute, Cardiff University, said:
“The much-anticipated announcement that the FDA has approved the use of aducanumab to treat Alzheimer’s patients is a cause for cautious celebration. Celebration because any progress in the development of effective drugs for this devastating disease must be welcomed; caution because the evidence base for the use of this drug is limited, evident from its very chequered history of trials failure and phoenix-like re-birth.
“The drug is hailed as the first to target a cause of Alzheimer’s disease, in this case, amyloid deposits in the brain which are broadly accepted to be one of the (several) drivers of the disease. Indeed, its capacity to reduce amyloid load in brains of some patients is striking; however, it has been much harder to convincingly demonstrate that amyloid reduction has significant impact on disease progression, the acid test of any Alzheimer drug. The evidence suggests that those patients with high amyloid load identified early in the disease process may benefit, but this is not a cure-all for Alzheimer’s. There remains a compelling need for new drugs, perhaps targeting other causative factors, that may have broader applicability and, critically, are more affordable (aducanumab is expected to cost $50,000 per year) for healthcare systems across the globe.”
Dr Mark Dallas, Associate Professor in Cellular Neuroscience, University of Reading, said:
“This is a watershed moment for Alzheimer’s disease with the FDA approving the antibody aducanumab. However, this sets a dangerous precedent for future drugs in the fight to combat Alzheimer’s and other complex diseases. In many ways the clinical trials undertaken do not present a clear picture that this medicine will be of tangible benefit to individuals living with dementia, indeed evidence indicated that approximately a third may suffer adverse side effects. It should be noted that the FDA has chosen a specific pathway called accelerated approval, basing their decision on the drugs ability to reduce amyloid beta rather than evidence of cognitive benefit. Therefore, while approval is a welcome announcement for those living with dementia the reality is somewhat less encouraging from a scientific standpoint.”
Prof John Hardy, Professor of Neuroscience, UCL, said:
“While I am pleased that aducanumab has received approval, we have to be clear that, at best, this is a drug with marginal benefit which will help only very carefully selected patients. We will need better amyloid drugs down the line and we will need other drugs which, for example, help deal with the tau/tangle pathology and which help microglia (the immune system of the brain) deal effectively with amyloid deposition. One could characterise this, not as the beginning of the end of Alzheimer’s, but as the end of the beginning in terms of treatments.”
Prof Bart De Strooper, Director of the UK Dementia Research Institute, said:
Summary: “With no effective therapies currently available to modify the progression of this devastating condition, this is a major milestone for the millions of people living with the Alzheimer’s. However, I fear the controversy and uncertainly surrounding the trials will limit the impact of this new treatment for the disease.”
“The FDA’s decision to approve aducanumab marks a hugely significant milestone in the search for much-needed treatments for Alzheimer’s. With no effective therapies currently available to modify the progression of this devastating disease, we all hope it proves a turning point for the millions of people living with the condition.
“The Alzheimer’s research field is however polarised on the aducanumab study findings, as some believe that the evidence for clinically meaningful benefits is not sufficient. There are still many barriers to overcome including cost, eligibility and clinicians’ enthusiasm to prescribe a medicine whose effects are far from certain. As we learn more about Alzheimer’s and the best times for treatment intervention, I’m sure we will see more refined therapeutics, likely in combination to target multiple biological components. The trial results appear to indicate that targeting the amyloid beta protein is a viable treatment option and worth pursuing. Indeed, there are other monoclonal antibodies currently in trials and the pharmaceutical company Eli Lilly recently released positive news about their Phase II trial of donanemab.
“In the last few years, I have seen encouraging progress in both our understanding of the mechanisms underlying neurodegenerative diseases like Alzheimer’s, and our approach to drug discovery and clinical trials. The search for treatments is difficult as the brain, and disorders associated with it, are extremely complex; there are likely multiple causes involving several biological pathways. Additionally, Alzheimer’s disease progresses over a very long time, with symptoms often only appearing decades after the first biochemical changes in our brain. We are now seeing a shift in clinical trial design whereby we can intervene earlier in the disease, saving large numbers of neurons. This is aided by the development of more precise blood biomarkers that can track stages of progression and predict those at highest risk of developing the disease.
“I sincerely hope that the outcome of this decision encourages our colleagues in the pharmaceutical industry. Now more than ever, we need investment in research and drug development for neurodegenerative diseases like Alzheimer’s, which is the most common cause of dementia. Dementia affects nearly 900,000 people in the UK and, with our ageing population, this is projected to rise to 2 million by 2050. In April, dementia overtook Covid-19 as the leading cause of death – a stark reminder of this growing and lasting health crisis. The pandemic has shown us that with sufficient funding and mobilisation of resources, we can make swift and significant progress against disease. If we apply that same urgency to dementia, I’m optimistic we will make further breakthroughs in treatments and improve the lives of those living with the condition.”
Prof John Gallacher, Director of Dementias Platform UK, said:
“This is exciting news for Alzheimer’s disease and good news for dementia research. Although I suspect this was a close decision, the FDA obviously gave aducanumab the benefit of the doubt.
“Apart from the chance for patient benefit, the scientific impact of this decision will be the real-world evidence it creates as the progress of people taking the drug is monitored.
“The decision will also act as a catalyst for further drug development: it will be interesting to see how many other companies dust down their own monoclonal antibodies for further work.”
Declared interests
Prof Richard Morris: “No conflicts of interest. I used to have collaborations with Elan, but these came to a conclusion 15 years ago.”
Dr Joseph Butchart: “No interest to declare.”
Prof Tara Spires-Jones: “No conflicts of interest with this story.”
Dr Elizabeth Coulthard: “I have been paid by BIOGEN for consultancy work and delivering educational videos and I was involved in delivering one of the aducanumab trials. I have also been paid by Novartis and UCB for consultancy work.”
Dr Ivan Koychev: “I am an investigator on a study testing a treatment for Alzheimer’s disease by Novo Nordisk.”
Prof Craig Ritchie: “has been a paid consultant for several companies developing treatments for Alzheimer’s disease over the last 5 years including Biogen, Eli Lilly, Merck, Roche, Janssen, Abbvie, Kyowa Kirin, Actinogen and Eisai. He was the UK Chief Investigator for the ENGAGE Trial and Academic Lead on the EPAD (European Prevention of Alzheimer’s Dementia) Programme which was a public:private partnership between the EU and several companies with an interest in developing treatments for AD His unit at the University of Edinburgh (Edinburgh Dementia Prevention) has received grant funding from Biogen, Janssen, AC Immune and Actinogen. He is the unpaid chairperson of the Brain Health Clinic Consortium established in the UK by Biogen.”
Prof Robert Howard: “No COI.”
Prof Paul Morgan: “No COI.”
Dr Mark Dallas: “Dr Dallas has received funding from Alzheimer’s Association and Alzheimer’s Research UK.”
Prof John Hardy: “I consult for Eisai (who are coapplicaqnts on this programme), but my consultation does not involve amyloid drugs. I consult for Eli Lilly on their amyloid programme.”
Prof Bart De Strooper: “I consult for Eisai although not to amyloid drugs or aducanumab. I have founded two spin off companies but they are not involved in amyloid programmes.”
Prof John Gallacher: “No relevant interests to declare on John’s part. Dementias Platform UK (DPUK) is an MRC-funded dementia research programme based at Oxford University.”
None others received.