Unlike currently available therapies – which only treat symptoms of the diseases – Aduhelm is the first therapy to target and affect the underlying diseases process of Alzheimer’s, notes the FDA.
The monoclonal antibody has been approved using the FDA’s accelerated approval pathway, which is designed for drugs for serious or life-threatening illnesses ‘that provides a meaningful therapeutic advantage over existing treatments’.
Under this pathway, the FDA requires Biogen to conduct a new randomized controlled clinical trial to verify the drug’s clinical benefit.
“As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation,” said Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research.
The FDA's decision has been the center of attention. Alzheimer's affects 6.2 million Americans, a devastating illness that can have a profound impact on patients and their families (worldwide, around 35 million people are affected, according to the WHO).
And yet the FDA acknowledges that data for the drug are 'complicated with respect to its clinical benefits'.
Aduhelm received a large setback in November, when the FDA's Peripheral and Central Nervous System Drugs Advisory Committee reviewed clinical trial data and said it did not believe one successful trial could act as the primary evidence supporting approval. (The drug had also failed to reach expectations in Phase III trials in 2019, but Biogen continued to pursue its development).
However, in approving the treatment today, the FDA says it "has determined that there is substantial evidence that aduhelm reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients."
The FDA's decision: Why is it important?
- Aduhelm is the first new treatment approved for Alzheimer's since 2003
- It is the first therapy to target the fundamental pathophysiology of the disease, rather than the symptoms
- Data for the drug is, as the FDA puts it, 'complicated'. Consequently, it has chosen the accelerated approval pathway, which requires a post-approval trial
- As the first approval in a new category, it is hoped the decision will invigorate investment and innovation in the field.
It notes the wide-spread attention in its decision, setting out its rational for its accelerated approval pathway.
"At the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward," said Cavazzoni of the FDA.
"We examined the clinical trial findings with a fine-tooth comb, we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee, we listened to the perspectives of the patient community, and we reviewed all relevant data.
"We ultimately decided to use the Accelerated Approval pathway—a pathway intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.
"In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy."
Alzheimer’s is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually, the ability to carry out simple tasks.
The accumulation of amyloid beta plaques in the brain is a defining pathology of Alzheimer's disease.
In clinical trials, Aduhelm reduced amyloid beta plaques by 59-71% at 18 months of treatment, according to Biogen and Eisai, who developed the drug.
The FDA notes that the late-stage development program for Aduhelm consisted of two phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline. The second trial did not meet the primary endpoint.
"In all studies in which it was evaluated, however, Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion. It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline," says the FDA, announcing the approval today.