From trial failure to trial success - is the reversal of fortune for aducanumab a potential treatment for AD?
New analysis has uncovered the true effectiveness of an Alzheimer’s drug, previously declared a failure leading to the halt of clinical trials 7 months prior to this realisation. This now ‘promising’ drug seems to be a source of light in the Alzheimer’s research space and could be the beginning of a great change in Alzheimer’s treatment.
Alzheimer’s disease (AD) is known to be the most common cause of dementia and predominantly affects those over the age of 65. Although it becomes progressively prevalent in older age, the changes that occur within the brain during Alzheimer’s disease are not normally associated with ageing. These changes include the continuous damage to nerve cells in the brain which lead to symptoms such as memory loss, repetitiveness, mood swings and uncertainty.
Current FDA approved treatment options for AD focus on the management and alleviation of symptoms rather than the prevention or cure of the disease. Although the exact trigger of Alzheimer’s disease is unknown, research into the pathogenesis of this neurodegenerative disease has shown that progression seems to coincide with the build-up of 2 proteins; amyloid and tau.
Subsequently leading to the formation of plaques and tangles, which not only disrupt signalling between neurons but can also induce damage to surrounding brain nerve cells. Plaques and tangles are now known to be major defining players in the onset and development of Alzheimer’s disease and is what research surrounding the disease revolves around.
Aducanumab (B11B037) targets aggregated Amyloid β (Aβ) by binding to the specific epitope present on the plaques, which is not present on the monomer of Amyloid (transmembrane protein found in brain nerve cells which normally contributes towards neural cell growth and repair).
By interacting with these plaques, Aducanumab could reduce the number of plaques found in the brain and in turn reduce the amount of signal disruption and nerve cell death caused by the plaques. Clinical trials for Aducanumab were halted in March this year by an independent monitoring committee due to insufficient evidence regarding the drug’s efficiency in treating the disease.
Last month, in a surprising turn of events, new data emerged from one of the discontinued studies and has shown that high doses of the drug reduce cognitive decline in patients with early AD. In fact, patients showed improvement in memory, orientation, language and in various daily activities, such as travelling independently or handling finances.
Biogen, the manufacturers of the drug, intend to attain and secure regulatory and federal approval for Aducanumab. Once news spread of the astonishing reversal of the drug ’s effectiveness, stock prices for Biogen and other companies investigating Aβ- targeting therapies shot up.
This new analysis has, in a way, confirmed the viability of the approach of targeting plaques to be effective, which was put into question following the halt of clinical trials in March.
This new data can also give rise to new approaches, such as combination therapies with pre-existing AD treatments that target AD from other avenues (e.g. inflammation, synaptic cell health and the immune system).
Although the FDA has allowed Biogen to file for approval of the AD drug, it is not clear if that approval will be granted. This is due to the trial that failed. It has been clarified that 2 trials were required to succeed in order for approval to be granted. However, it has also been explained that in this failed trial, fewer patients were given the higher dose for the sufficient period of time.
Biogen still has a lot of hard work ahead of them to make their case and prove the effectiveness of their drug. They will be filing for approval in early 2020 and if successful, hope to offer this new drug to the patients previously enrolled on the studies.
The fate of Aducanumab is unknown for now, but this doesn’t change the fact that this has been a ‘game-changer’ for the field of AD therapy.
The potential success of this new treatment holds great weight, as it could possibly be the first disease-altering therapy for AD.