Medical News
Hopes dashed for Alzheimer ’ s breakthrough after trial results called into question
Long wait for effective dementia treatment continues
C
ontroversy is never far away from Alzheimer ’ s research , where differing schools of thought about the cause of the degenerative neurological condition can spark heated debate among scientists .
Disputes typically centre around the amyloid hypothesis , which holds that the accumulation of the beta-amyloid protein in the brain is behind the disease . This is furiously countered by advocates who argue it comes from the formation of neurofibrillary tangles produced by the abnormal accumulation of a protein called tau that collects inside neurons .
But now a new controversy has emerged , this time concerning the results of trials of a new anti-Alzheimer ’ s drug , donanemab . Researchers had reported the drug had cleared some areas of amyloid plaque in the brain and led to some slowing decline in its creation .
Drugs like donanemab that target the accumulation of amyloid have had a long history of showing promise in early trials before falling short in larger , phase 3 tests .
The results were touted as an exciting development , but many researchers point out that the effect was actually quite small in the drug ’ s second trial phase , after the results were presented by its developer , Eli Lilly , at a major conference in March .
One of the major issues was the decision to use a scale developed by Eli Lilly itself , rather than one of the traditional and well-established scales used for the purpose of testing the efficacy of therapies .
The study followed 257 patients with early stages of Alzheimer ’ s over the course of 76 weeks . The primary endpoint of the study was measured by scores on an integrated Alzheimer ’ s disease rating scale , which has not traditionally been used in such trials .
The developer claimed that its results met its primary goals , although the overall benefit shown has been criticised by Alzheimer ’ s experts for not being clinically meaningful , and they say that it ’ s unlikely to show a significantly greater magnitude of effect in the third phase of trials .
Dr Lyndsey Collins-Praino , a behavioural neuroscientist and associate professor at the University of Adelaide , has urged caution when interpreting the trial results , even though it would be tempting to hail an advance in a field that has gone nearly two decades without a major breakthrough .
“ The fact that the drug didn ’ t meet statistical significance on any of its outcomes is quite concerning ,” she told Global Health Asia-Pacific . “ Some of the choices that they made in their trial design , and the way in which they looked at their data , were unusual when you consider how you might ideally design the trial to look at these measures . I think we have to proceed with particular caution .”
Eli Lilly had hoped to accelerate the third phase trials and explore the possibility of gaining accelerated approval — a tool used for drugs that treat serious diseases where no or few other options exist — based on the earlier trials .
In another development , the American drug regulator has granted clearance to the first new Alzheimer ’ s treatment in nearly two decades , although its effectiveness is in doubt among many in the scientific community .
The new drug , Aduhelm , works by attacking betaamyloid , the protein clumps that form plaque , to slow cognitive decline , albeit marginally . However , it is not a cure for Alzheimer ’ s , and it does not reverse the disease ’ s progression .
In approving the drug on a conditional basis , the US Food and Drug Administration departed from decades of regulatory precedent , setting a new bar for treatments with considerable potential but unproven benefit .
Aduhelm ’ s manufacturer , Biogen , will now need to complete a large clinical trial to confirm that removing the plaque has cognitive benefits .
“ This historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer ’ s disease ,” Michel Vounatsos , the chief executive of Biogen , said in a statement . Others are less euphoric , Dr Collins-Praino among them .
“ Every trial ever attempted in amyloid targeting therapy has failed , yet we still continue to go after it even though the other pathological marker of Alzheimer ’ s , tau , is better correlated with cognitive impairment and disease progression , and it arguably might make it a better target . But the field is absolutely fixated on the amyloid hypothesis ,” she said . n
26 JUNE 2021 GlobalHealthAsiaPacific . com