December 5, 2019

expert reaction to Biogen’s presentation on the drug aducanumab for Alzheimer’s at the CTAD Conference

The pharmaceutical company Biogen has presented its plans for the drug aducanumab for the treatment of Alzheimer’s at the CTAD Conference.

Dr Diego Gomez-Nicola, Associate Professor, Principal Investigator in Neuroimmunology, University of Southampton, said: 

“Today Biogen presented the topline results from the EMERGE and ENGAGE studies, for testing the efficacy of the anti-amyloid agent Aducanumab in MCI and Mild-AD patients. These results are hugely important for the field, as for the first time demonstrate efficacy of a treatment for Alzheimer’s disease. 

“EMERGE and ENGAGE were designed as twin studies, but due to some divergence in recruitment and changes in the protocol, different patients received different cumulative doses of Aducanumab. In EMERGE the patients received higher cumulative doses, and this led to significant improvement in the cognitive decline, results not observed in ENGAGE. The data presented today is in line with the proposed mechanism of action, and suggests that the prolonged exposure to an anti-amyloid agent could be a treatment for Alzheimer’s disease. This is a very exciting and encouraging prospect for a disease lacking any effective disease-modifying agent, to date. However, there is room for improvement, as the efficacy was mostly observed by the end of the trial, after 78 weeks of treatment, generating a challenging clinical prospect. Also, the results suggested that lower doses caused a significant clearance of amyloid, yet failing to improve cognition, suggesting that anti-amyloid treatments could be borderline of driving efficacy for many patients. Despite these caveats, today is a bright day for the fight against dementia, and finally the field is starting to approach an effective treatment for this devastating disease”

Dr Carol Routledge, Director of Research at Alzheimer’s Research UK said:

“Since Biogen announced unexpected positive results from two phase III clinical trials of aducanumab, the field has been waiting to see more detailed data. The positive news is that, given the long wait for a disease-modifying drug for Alzheimer’s, aducanumab shows a clear effect on key hallmarks of the disease. The additional data provides an explanation for why the two phase III trials may have showed such different top-line results, suggesting people benefitted more when on a higher dose for a longer period of time.

“Regulators now have a critical decision to make – are the benefits seen in these two 18-month-long trials large enough to make a meaningful difference to the lives of people with dementia? That decision will ultimately determine who may get access to aducanumab, and other drugs like it, in future and under what restrictions. We are now in unchartered territory for an Alzheimer’s drug, and there will be huge anticipation around how the FDA decides to proceed.

“Studies like these add hugely to our understanding of diseases like Alzheimer’s and the best approach to treat them. Dementia research is making strides and gaining momentum. It’s testament to the commitment of scientists, funders and those who take part in trials like this that we’re moving closer to the first life-changing treatment for Alzheimer’s.”

Dr James Pickett, Head of Research at Alzheimer’s Society said:

“The results presented at CTAD today were of two trials of the anti-amyloid drug aducanumab that were stopped in March 2019 because they were deemed unlikely to work at that time.

“Following the results presented today, it’s not possible to be sure whether people in the early stages of Alzheimer’s disease would meaningfully benefit from aducanumab. The drug company is collecting more data which may help further answer this question over the coming months. It’s now also the role of the drug regulators to scrutinise the data to find out if on balance, there is a benefit to people with Alzheimer’s disease.

“With very few other treatment options for Alzheimer’s people may ask ‘What is there to be lost?’ in making this drug available now, but it’s crucial we fully understand the impact and safety of this drug. We await the outcomes of discussions with the FDA in USA and European Medical Agency next year.

“Whatever the fate of aducanumab may be, without dementia research we simply would not have reached this point. 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. We are committed to supporting ground breaking research so that we can bring new treatments to everyone affected by dementia.”

Dr Ivan Koychev, Senior Clinical Researcher, Dementia Platform UK, University of Oxford, said:

“This is an important announcement showing that an antibody targeting the build-up of amyloid in the brain results in a meaningful reduction (20-30%) in the speed of decline as measured by memory/thinking skills loss but also crucially how well individuals manage day-to-day tasks. The result of one of the two studies reported hinges on a complex change to the study protocol that resulted in more individuals being exposed to the higher, arguably more effective, dose of the drug. How exactly this change was implemented will need further examination and debate when the data becomes available. The drug appears to be safe although a proportion of people (10-40%) developed a reaction to the drug (Amyloid-related imaging abnormalities, ARIA) that can be seen using head scans (MRIs) – while it was said that this was not associated with significant symptoms and resolved spontaneously, it is unclear what the impact of this side effect will be in people treated long-term. Looking to the future, the fact that the drug showed a very strong and consistent effect on reducing amyloid build-up in the brain (assessed using Positron Emission Tomography head scan) opens the door to studies targeting individuals at the earliest stages of disease which is where the main benefit from the drug may come from. From the NHS point of view the availability of this drug will pose a question regarding how we diagnose and manage dementia. The drug will require a test to evidence build up of amyloid in the brain (either using spinal tap or Positron Emission Tomography head scan) as well as likely genetic testing due to concerns that patients at higher genetic risk may be particularly prone to developing the reaction to drug mentioned earlier (ARIA). Neither the amyloid nor the genetic test are routinely available to NHS clinicians and thus the roll-out of this treatment will require significant resource investment to set up expertise and facilities to deliver these tests in addition to the cost of the drug itself.”

Prof Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said:

“The outcome of a trial called EMERGE, in more than 3,000 people with Mild Cognitive Impairment due to Alzheimer’s disease or mild Alzheimer’s disease, demonstrated that high doses of aducanumab could reduce decline in function by 40 percent compared to placebo, over 18 months.  There were also significant overall global benefits and benefits in cognition on a memory test. 

“Maintaining function is incredibly important in people with mild-to-moderate dementia. It helps people to continue performing the everyday tasks that mean they can live independently, so a 40 per cent reduction in decline is an excellent result that could have a really significant benefit on the lives of people with dementia and their families. The second trial, ENGAGE, had a very similar design, except that many people in the high dose arm received a comparatively lower dose than those in the high dose arm of EMERGE.  The results were less clear, with benefits only apparent in the sub group of the participants who had the highest dose permitted. The question now is whether aducanunab should be approved, or whether a final phase III trial of the full high dose aducanumab is needed to be sure of these benefits.”

https://www.ctad-alzheimer.com/

Declared interests

Dr Diego Gomez-Nicola: I have no conflicting interests related to this.

Dr James Pickett: No conflicts

Dr Ivan Koychev: I have no relevant conflicts of interest.

Prof Clive Ballard: No conflicts

None others received