The future of aducanumab, Biogen’s experimental treatment for Alzheimer’s disease, remains uncertain. This came after an independent advisory panel concluded that there was insufficient evidence to show that the drug was effective in slowing cognitive decline in Alzheimer’s patients. When asked whether a clinical study provided strong evidence that the drug effectively treated Alzheimer’s, eight out of 11 experts voted “No”. The panel also rejected a second study on the drug with seven ‘No’ and four ‘Uncertain’ votes.
The peripheral and central nervous system medicines advisory committee convened on November 6 by order of the US Food and Drug Administration (FDA). Finally, the committee voted 0 ‘Yes’, 10 ‘No’ and 1 ‘Indeterminate’ to the following question, ” In view of the exploratory analyzes provided by Study 301 and Study 302, the results and evidence of Study 103 are based on a pharmacodynamic It makes sense to consider Study 302 as the primary evidence of the efficacy of aducanumab for the treatment of Alzheimer’s disease, since it has efficacy? ”
Professor of epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health, Dr. “There are literally a dozen different red threads that signal concerns about the consistency of the evidence,” said Caleb Alexander. He added that “the FDA does not understand how it can conclude that there is substantial evidence of efficacy.”
“The treatment of Alzheimer’s is a huge, urgent, and unmet need. If we confirm something with not strong data, we risk delaying good and effective treatments,” another panelist Dr Joel Perlmutter from the University of Washington School of Medicine told NBC News. .
Alzheimer’s disease is a progressive neurodegenerative disorder that slowly destroys memory and thinking skills, and then the ability to perform daily activities. More than 5.5 million Americans live with this disease. There is currently no approved drug that can reverse the mental decline of Alzheimer’s. The FDA has approved medications for Alzheimer’s to help symptoms.
What is aducanumab?
It is an investigational human monoclonal antibody that has been studied for the treatment of Alzheimer’s disease. Medication does not cure or reverse Alzheimer’s disease. According to Biogen, “it has the potential to influence the underlying disease pathophysiology, affect slow cognitive and functional decline, and benefit patients’ ability to carry out daily living activities, including carrying out personal finances, doing housework, such as cleaning, shopping, and doing laundry and independently out of the home. don’t go out. ”
Aducanumab targets a compound known as beta-amyloid in the brain that is thought to play a role in devastating disease. Since October 2017, Biogen and Eisai have been collaborating for the development and commercialization of aducanumab globally.
In March 2019, Biogen stopped Phase 3 trials of the drug after an independent data monitoring committee determined that the drug would not work. However, Biogen later announced that it was seeking regulatory approval for aducanumab. The company said later results show that one study is positive and one is negative. He added that an independent study provided “consistent evidence”. “Continuous exposure to 10mg / kg aducanumab is effective in reducing clinical decline in patients with early symptomatic Alzheimer’s disease,” the company said.
What did FDA say?
Before the meeting, a 343-page FDA document said the results of Biogen’s end-stage trial were “robust”, “extremely convincing,” and the study could “provide a primary contribution to demonstrating important evidence of efficacy”. aducanumab.
The report also explained that aducanumab has an “acceptable safety profile” to support its use in people with Alzheimer’s disease. “Based on the above considerations, the applicant has provided substantial evidence that it is effective in supporting approval,” the agency added.
However, not every FDA commentator is convinced. An expert embedded in the FDA document wrote that “the second (negative) study directly contradicts the negative study”, stating that a single positive trial of aducanumab cannot overshadow the negative one. The reviewer concluded, “There is no convincing, substantial evidence that the treatment effect or disease is slowing, and another study is needed to confirm or reject positive study and negative study.”
Prior to the meeting, the Alzheimer’s Association presented a letter stating that it was a “dire and dire need” to offer help and support to millions of Americans who are affected every day by the “overwhelming realities of Alzheimer’s.”
Dr. David Knopman commented before the trial, “perfection may be the enemy of the good, but aducanumab, the evidence is not even getting better. “Contrary to the hope that aducanumab will help Alzheimer’s patients, the evidence shows that it will not cure any of them, hurting some of those exposed and will consume enormous resources,” he warned.
Dr Knopman, a professor of neurology at the Mayo Clinic, recommended that the solution should be done in another trial with Biogen’s high-dose aducanumab. “If the benefits of the drug are really important, such a trial can be recruited quickly and only a few hundred patients need to be randomized,” he suggested.
While the FDA has historically done this, it does not have to follow the guidance committee’s recommendations. If approved, the drug will be the first new treatment for Alzheimer’s in about twenty years. The FDA is expected to make a decision by March 2021.
Commenting on the panel’s decision, Biogen CEO Michel Vounatsos said, “Biogen thanked the many patients and advocates who shared their personal thoughts and experiences at today’s advisory committee meeting, reflecting the important unmet need for Alzheimer’s treatment. We appreciated the opportunity to share our data with the Advisory Committee, and we will continue to work with the FDA as we complete the review of our application. “