The US Food and Drug Administration (FDA) announced on Monday, June 7, the authorization of a new drug targeting the causes of Alzheimer’s disease. Baptized Aduhelm, it is produced by the pharmaceutical company Biogen. “It’s the first approved treatment for Alzheimer’s disease since 2003 and the first therapy which targets the fundamental pathophysiology of the disease “, underlines the FDA (source 1).
Dr. Maï Panchal, Scientific Director of the Vaincre Alzheimer Foundation, comes back with us on the “historic approval” of this immunotherapy.
What does this new treatment consist of?
Dr. Panchal: “The Aduhelm uses a human monoclonal antibody baptized aducanumab. This molecule attacks the beta-amyloid protein, which in Alzheimer’s patients aggregates in the form of plaques around neurons and prevents them from functioning normally. The drug is administered intravenously : the antibody circulates in the blood, crosses the blood-brain barrier (which separates the bloodstream from the central nervous system) and dissolves amyloid deposits in brain tissue. ”
What are the benefits of Aduhelm for patients?
Dr. Panchal: “During the last clinical trials conducted by the Biogen laboratory, it was found that the reduction of amyloid plaques was correlated with a beneficial effect on symptoms: the teams observed a slowing of cognitive decline in Alzheimer’s patients.
We cannot yet claim victory, because it is not an improvement, but a slowing down of the decline of cognitive functions. It is not a cure. We still do not know how to stop the progression of Alzheimer’s disease. The goal of the Aduhelm is therefore not to eradicate the disease, but to live with it, at best, while maintaining its autonomy as long as possible. ”
Who are the patients concerned by this immunotherapy?
Dr. Panchal: “Both clinical trials were conducted on patients with early-stage Alzheimer’s. Aduhelm should therefore be effective at the onset of the disease, when symptoms are still mild. An upcoming clinical trial should shed more light on the ideal patient profile and further studies are needed to determine the frequency, duration and dosage of treatment. For patients at a more advanced stage, there is unfortunately a risk of not seeing cognitive improvement. ”
What are the possible side effects of Aduhelm?
Dr. Panchal: “The side effects of this immunotherapy concern 2% of patients. The laboratory is mainly responsible for headache and falls, sometimes severe allergic reactionsduring the infusion : swelling of the face, lips, mouth or tongue and hives (source 2). But what seems more difficult to monitor and take charge of is the ARIA effect (amyloid-related imaging abnormalities): Micro-bleeding or edema in certain areas of the brain, which requires follow-up with MRI. This medical follow-up seems rather heavy and has not yet been specified by the laboratory. ”
Why did this medicine have an emergency procedure? What are the next steps ?
Dr. Panchal: “The FDA has put in place a expedited authorization procedure (the equivalent of a temporary authorization for use in France). It is a relatively common procedure It accepts the use of the treatment, provided that the Biogen laboratory conducts additional clinical trials, post-authorization, to verify the clinical benefits of the drug. If the results prove to be disappointing, it will withdraw its authorization.
At the scientific level, we remain quite mixed for the moment. The first two trials presented by Biogen were identical. One was positive – aducanumab did slow cognitive decline. But the other turned out to be rather negative. Initially, the FDA advisory committee therefore issued an unfavorable opinion for its marketing. Then, under pressure from American patient associations, she finally chose the accelerated procedure which allows her to require an additional clinical trial.
Initially, the patients who will be able to benefit from the Aduhelm treatment are those who will be recruited in the post-authorization clinical trial. But until the laboratory has provided precise data concerning its administration methods (who is the medicine for? how long does the treatment last? where can it be given? what follow-up for patients?), it is possible that this treatment is used inappropriately in patients with advanced stages of disease.”
Could Aduhelm be authorized in France?
Dr. Panchal: “The Aduhelm could potentially be authorized in Europe, then in France in the medium term. It is hoped that Biogen will submit a dossier to theEuropean Medicines Agency (EMA) in the course of the year 2021. The laboratory has not yet communicated on this subject, but the decision taken by the FDA will certainly allow the procedures to be speeded up. ”
Where is the search for treatments for Alzheimer’s disease?
Dr. Panchal: “More than 126 molecules are currently in clinical trials around the world. 28 molecules are evaluated in phase 3 of clinical trials. Among them, some target only the symptoms of Alzheimer’s disease, others target factors such as tau protein, neuroinflammation or vascular disorders, still others target the beta-amyloid protein (three immunotherapies currently in phase 3 of clinical trials).
Considerable progress has been made over the past few years, but it takes time. The beta-amyloid for example, was discovered in 1984 and it took 37 years to develop immunotherapy which seems to produce interesting effects. It’s a immense source of hope for patients and their families, but we must remain cautious and continue to support research. ”