The U.S. Food and Drug Administration (FDA) just gave the green light to aducanumab (marketed as Aduhelm), the first Alzheimer’s-specific drug to be approved in nearly two decades , but it has done so amid strong controversy. The FDA has used the ‘expedited approval’ pathway, a mechanism that allows the agency to ‘authorize a drug for a serious or life-threatening disease that can provide significant therapeutic benefit over existing treatments even when there is some uncertainty about the clinical benefit of the drug ‘.
In addition, the FDA has highlighted in its statement that the most significant thing about Aduhelm is that it is the first treatment to target the underlying pathophysiology of Alzheimer’s disease: the presence of beta amyloid plaques in the brain. Clinical trials of the drug would have shown a significant reduction in these plaques in the group of patients who received the treatment. The same agency acknowledges, however, the controversy surrounding the approval of this drug, and explains that the last stage consisted of two phase 3 clinical trials: one of them met the approval criteria and the other did not. “However, in all the studies in which it was evaluated, Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent manner. The reduction in amyloid plaque is expected to result in a reduction in clinical decline, ”argues the FDA.
Experts ask for caution
Alzheimer’s is a devastating disease and many families are pinning their hopes on a potential cure or alleviation of the cognitive decline associated with its relentless progression. Therefore, and given the doubts generated by the results of the tests, the experts ask to take this news with great caution. In Spain, the Behavior and Dementia Study Group of the Spanish Neurology Society (SEN) has issued a statement in which it clarifies that “the available data indicate that this drug at high doses takes several months to eliminate amyloid plaques of patients’ brains that have accumulated over years, or even decades . It would seem that only when a radical reduction of the amyloid load (a practical reversion to normality) is achieved in a sustained manner and in the initial stages of the disease, could the clinical benefit of patients begin to be appreciated. This tells us that long studies are necessary to be able to evaluate the efficacy of these drugs ”.
In addition, the SEN recalls that the European Medicines Agency (EMA) has not yet given its approval to the drug, and the decision on its approval will take place in the coming months. “Finally, many aspects remain open, such as the cost of the drug, with significant discrepancies between the market price estimate that various media have collected (unaffordable both for a public health system and for an average family economy) and the costs estimated by different sources depending on the expected effectiveness ”.
On the other hand, pharmaceutical companies are required, after approval of the drug, to conduct what are known as confirmatory phase 4 trials. If these studies do not verify the anticipated clinical benefit of the drug, the FDA could withdraw it from the market.
In any case, SEN experts believe that, despite the controversy surrounding the approval of aducanumab, it is time to look hopefully at the future of the fight against Alzheimer’s disease. “This approval reflects the exciting moment we find ourselves in in Alzheimer’s research and fight and may be a turning point. It is now possible to modify key pathophysiological processes of the disease with possible clinical benefit. Despite the doubts that the FDA approval of aducanumab may raise, we should welcome the tremendous strides we have made in the field of Alzheimer’s disease in recent decades . “
The signatories of the statement have taken the opportunity to demand a profound improvement in the care of people with Alzheimer’s in our country: “Our patients must be able to benefit from quality neurological care throughout the territory. In addition, any disease-modifying therapy will require an early diagnosis with the support of biomarkers and for this we need more neurologists who are experts in dementia integrated in multidisciplinary units (with experts in neuropsychology, advanced practice nurses, health social workers, etc.) with access to technology and day hospitals. Our healthcare system is by no means up to the challenge. Today, more than ever, it is necessary to design an Alzheimer’s plan that puts the necessary resources to offer early and accurate diagnoses , and to be able to be prepared to give these treatments to our patients with equity throughout our country ”.
