How effective is the new drug for Alzheimer’s disease – Aducanumab (market name Aduhelm)?
Summary:
- Alzheimer’s disease is a neurodegenerative illness which progressively decreases cognitive abilities and, in the latest stages, results in the patient’s death.
- While there are drugs easing symptoms, there is currently no cure for Alzheimer’s disease.
- Aducanumab does not cure Alzheimer’s disease but can help reduce cognitive decline in some patients.
Besides the ongoing SARS-CoV-2 pandemic, there are still many other diseases that we, as a society, have to struggle with on a daily basis. While cancer and heart diseases cause a lot of suffering and death, Alzheimer’s disease might very well be one of the most tragic afflictions with a high death rate worldwide.
Alzheimer’s is the sixth leading cause of death in the United States in the general population, and the third for older people [1]. Alzheimer’s is characterized by the anomalous accumulation of two distinct structures in the brain i.e., amyloid plaques formed from amyloid-β fibrils, and tau neurofibrillary tangles, which can be recognized as abnormal clumps and tangled bundles of fibers, respectively [2]. As the cause of Alzheimer’s is not yet fully understood, one of the hypotheses suggests that the accumulation of amyloid-β fibrils could have a toxic effect and be responsible for its outcome and progression [3, 4]. It is truly devastating as it damages the brain, leading to progressively more severe cognitive impairment. The progress of Alzheimer’s disease can be split into three stages: mild, moderate, and severe. It starts with memory loss and problems with the effective fulfillment of daily tasks. Furthermore, behavior and personality changes can also be observed. As the disease progresses, memory loss becomes more severe, often leading to people not recognizing their friends and family members. These symptoms may occur in parallel with impulsive behavior caused by hallucinations, delusions, or paranoia. In the last stage of Alzheimer’s, the patient’s communication capabilities are entirely lost, resulting in the need for constant care [1].
Furthermore, there is no cure for this disease. While the currently available therapies can only ease the symptoms, they cannot stop the progression of the disease itself [5]. For these reasons, recent FDA (the US Food and Drug Administration Agency) approval for a novel drug targeting amyloid-β fibrils, called Aducanumab (market name – Aduhelm) [3, 6] was met with many hyper-optimistic news headlines [7-9]. Some of them even employed words like “miracle” to describe this new drug [7, 8]. FDA approved Aducanumab under the so-called “accelerated approval”, a protocol that comes with some additional requirements. While the drug can be used for therapy against Alzheimer’s, the manufacturer has to conduct additional clinical trials to confirm the initial clinical benefits. Furthermore, the allowed timeline for such verifications is limited. Indeed, the final protocol has to be submitted until August of 2022 and the final report of the clinical trials has to be submitted until February 2030. Otherwise, the drug will have to be revoked [6].
The FDA committee based their decision on outcomes from three clinical trials, of which two were large, international cohorts during the third phase (Clinical Trials Explained) [10-12]. Unfortunately, while one of them presented a significant reduction of patients’ cognitive decline when compared to controls (patients receiving placebo treatment) [12], the other study did not show a compelling difference between these two groups [11]. However, a reduction of the amyloid plaques has been observed in all participants under Aducanumab treatment. Therefore, combining the lack of certainty regarding Alzheimer’s disease origin, the proven reduction of the amyloid plaques in treated patients, and the positive cognitive outcome in many patients during the trials, the FDA decided to grant limited approval for Aducanumab, despite the remaining uncertainties of the clinical benefits [13].
In summary, as pointed out in the FDA’s clinical review, we are in desperate need of effective therapy against Alzheimer’s disease. While Aducanumab unfortunately is not the miracle drug some were hoping for, it is a promising drug for patients struggling with Alzheimer’s as its current results present it as a better option than other contemporary therapies and it might prove useful as a part of a future multidrug approach [14].
References:
- NIA, Alzheimer’s Disease Fact Sheet, in NIH: National Institute on Aging. 2021, NIH: National Institute on Aging: nia.nih.gov.
- Arndt, J.W., et al., Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-beta. Sci Rep, 2018. 8(1): p. 6412.
- Sevigny, J., et al., The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature, 2016. 537(7618): p. 50-6.
- Tolar, M., et al., Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res Ther, 2020. 12(1): p. 95.
- Ferrero, J., et al., First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer’s disease. Alzheimers Dement (N Y), 2016. 2(3): p. 169-176.
- FDA, Aduhelm BLA ACCELERATED APPROVAL F.C.f.D.E.a. Research, Editor. 2021, FDA: FDA.gov.
- Bagot, M., Dementia miracle as drug that slows disease set to get approval sparking ‘huge hope’, in Mirror. 2021: mirror.co.uk.
- Hodge, M., ALZ HOPE Miracle’ Alzheimer’s drug that slows dementia could be approved in days and available on NHS next year, in The Sun. 2021: thesun.co.uk.
- Park, A., The First Treatment for Alzheimer’s Disease Is Here, in TIME. 2021: time.com.
- Biogen, Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer’s Disease (PRIME). 2020, NIH: ClinicalTrials.gov.
- Biogen, 221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer’s Disease (ENGAGE). 2021, NIH: ClinicalTrial.gov.
- Biogen, 221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer’s Disease (EMERGE). 2021, NIH: ClinicalTrials.gov.
- Cavazzoni, P., FDA’s Decision to Approve New Treatment for Alzheimer’s Disease. 2021, FDA: FDA.gov.
- Krudys, K., Aduhelm (aducanumab) FDA CLINICAL REVIEW, F.C.F.D.E.A. RESEARCH, Editor. 2020, FDA: FDA.gov.