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A conference abstract (not a published paper) presented at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2022 compares the drugs donanemab and aducanumab on amyloid lowering in early symptomatic Alzheimer’s Disease.
Dr Ivan Koychev, Senior Clinical Researcher at the University of Oxford, said:
“This is a ‘mechanistic’ clinical trial, i.e. looking at a change in a laboratory measure rather than clinical benefit. These trials can be used early in the development in small groups of patients (in this case under 100 in each group vs the 1000s generally required for efficacy trials) to establish if a drug is hitting the right target. These trials are not useful on their own in proving that the drug has benefit for dementia. In this case, the amyloid anti-body therapy donanemab was tested in terms of its amyloid clearance properties to aducanumab – donanemab did considerably better while the two drugs had similar safety profile. Overall, this is an interesting result as it shows strong amyloid clearance through donanemab but it remains to be seen whether this translates into a clinical benefit.”
Prof Bart De Strooper, Director of the UK Dementia Research Institute, and Group Leader at the UK Dementia Research Institute at UCL, said:
“This is a technical paper, helping show that donanemab is a drug worth investigating. We have already had interesting phase II results some months ago and are eagerly awaiting the phase III results. It is also preliminary to be commenting in much depth on an abstract without the full dataset being available.”
Prof Jonathan Schott, Professor of Neurology, Dementia Research Centre, UCL, said:
“In this rare head-to-head study of two potential treatments for Alzheimer’s disease both broadly targeting the same pathology, the major finding was that donenemab was significantly better at removing beta-amyloid from the brain than aducanumab over a six-month period, but that both drugs had broadly similar safety profiles. If better clinical outcomes are associated with more beta-amyloid removal, these findings hold promise that donanemab may be more effective than aducanumab – whose approval in the USA has been dogged by controversy over efficacy and cost. And, if robust removal of amyloid can be achieved quickly shortening the time-frame over which drugs needed to be given, then this would also have significant implications for clinical practice. The results of the pivotal clinical trials of donanemab expected next year are awaited with much anticipation.”
Prof John Hardy, Professor of Neuroscience, UCL, said:
“It will of course, be great to see the phase 3 results from the donanemab trial around June next year. What this trial shows is that donanemab has a similar overall effect to aducanumab in terms of its amyloid removal but seems as if it a “stronger” drug (more amyloid removal). This gives further hope that we may have more effective therapies for Alzheimer’s next year and of course, competition may bring down prices.”
The abstract ‘LB3 – TRAILBLAZER – ALZ4: TOPLINE STUDY RESULTS DIRECTLY COMPARING DONANEMAB TO ADUCANUMAB ON AMYLOID LOWERING IN EARLY, SYMPTOMATIC ALZHEIMER’S DISEASE ’ was presented at CTAD at 23:00 UK time Wednesday 30 November.,
Declared interests
Dr Ivan Koychev is in receipt of an investigator-initiated clinical trial grant by Novo Nordisk testing semaglutide’s effects on Alzheimer’s pathology.
Prof Bart De Strooper: “I have been consultant for a series of pharmaceutical companies, including Eisai, and I am myself scientific founder of two biotech companies. However I have never consulted for their antibody programs and I have myself no direct interest in antibody therapies.”
Prof Jonathan Schott: “I have consulted for Biogen and Eli Lilly.”
Prof John Hardy has consulted for Eisai, Roche and Eli Lilly in the last year (but not on their antibody trials).
For all other experts, no reply to our request for DOIs was received.