The Food and Drug Administration (FDA) approved the drug Aduhelm (aducanumab) for the treatment of Alzheimer’s on June 7, despite not recommending the drug by its own expert advisory panel.
The FDA has approved the fast track Aduhelm when there is an urgent need to authorize a drug for a serious or life-threatening illness; when a drug can provide significant therapeutic benefit compared to other existing treatments, and when there is a high likelihood of benefit to patients, even if some uncertainty remains about the drug itself.
Aduhelm is the first drug approved for the treatment of Alzheimer’s disease since 2003. More importantly, it is the first drug to target the pathophysiology of Alzheimer’s, the presence of beta-amyloid plaques in the brain.
Alzheimer’s disease is a neurodegenerative disease characterized by the death of nerve cells in the brain. It is the most common form of dementia (up to 70% of all cases) and one of the most poorly understood. No cure has yet been developed for this disease. There is a hypothesis that beta-amyloids, protein complexes formed from a membrane protein, lead to disease. They can form insoluble clumps or plaques, which are signs of illness. The FDA believes that taking Aduhelm reduces the number of these plaques.
“Given that this is a serious, life-threatening disease, it makes sense that a lot of people followed the test results,” the FDA said in a statement. – In addition, the data presented left some uncertainty about the clinical benefits of this drug. And, as is often the case when interpreting scientific data, the expert community offers different points of view. We have reviewed all opinions, thank the Advisory Committee for the independent review of the data, and have determined that the evidence presented in the Aduhelm approval application meets the fast-track approval standard. The benefits of the drug for patients with Alzheimer’s disease outweigh the risks.
Following the results of two identical Phase III trials, EMERGE and ENGAGE trials were discontinued. In March 2019, it was decided that the effectiveness of treatment in the group receiving the drug did not differ much from the “treatment” of those who received a placebo. Manufacturing company Biogen acknowledged these findings, but changed its position in the fall of 2019, announcing that when the number of doses increased, the drug improved memory retention, the ability to think and communicate, and that the ENGAGE study was productive. In November 2020, an FDA advisory committee voted overwhelmingly against the drug’s approval, saying that positive results for the same drug obtained in one of two trials cannot be considered separately, but should be considered together. In March 2020, Biogen began another study called EMBARK. It includes 2,400 patients with Alzheimer’s disease. It should end only in the fall of 2023.
In its statement of the decision, the FDA mentions the failed results of the first two trials, but notes: “However, in all studies, Aduhelm consistently and very convincingly reduced the level of beta-amyloid plaques in the brain in a dose-dependent manner.” Therefore, the FDA will continue to monitor and require Biogen to complete the EMBARK clinical trial despite the approval. “If the drug does not work as intended, we will remove it from the market. But we hope that as more people take Aduhelm, we will see evidence of its benefits, ”the agency said.
In addition, doctors, when prescribing this medicine, are obliged to warn about side effects. The most common symptoms were acute respiratory infections, headache, loss of consciousness, disorientation, delirium, diarrhea, urticaria, and Quincke’s edema.
– The currently available therapies are directed only to the symptoms of the disease; this drug is the first to target the underlying process of Alzheimer’s disease, ”said Dr. Patricia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research.
The news, as expected, caused a heated debate among specialists. On the MedScape forum, the overwhelming majority of doctors opposed the FDA’s decision.
– Today we are approving drugs by requesting a randomized controlled trial in the future to see if a drug should be approved. It’s a sad day for medicine and a great day for Big Pharma, wrote neurologist Alex Cooper.
Sales of the new drug are estimated at $ 62.7 million in 2021. If the drug is successfully marketed, sales could grow to $ 603.2 million in 2022 and $ 1.6 billion in 2023. Biogen’s shares soared 38% after the FDA’s decision was announced. The company said the annual treatment would cost $ 56,000. Preliminary analysis has shown that the drug will be cost-effective at a cost of $ 2,500 to $ 8,300 per patient per year.
Insurance company Cigna estimates that about six million Americans suffer from Alzheimer’s. According to the Centers for Disease Control and Prevention (CDC), 121,499 people died from Alzheimer’s in the United States in 2019, 54% more than a decade earlier.