Since the June 2021 “accelerated approval” of Biogen’s Alzheimer’s drug, Aduhelm, all eyes of the medical community, investors, and the public have been on the company to finalize the results of its Phase 4 confirmatory trial. As the results of the confirmatory trial were released by Biogen in early November 2021 at a conference for Alzheimer’s research and development, the public also became aware of the first likely Aduhelm-related death.
What is FDA Accelerated Approval?
On June 7, 2021, Biogen’s drug, Aduhelm, met “accelerated approval” requirements under regulatory standard 21 CFR 601.41 and was subsequently approved by the FDA.
According to the FDA’s website, theAccelerated Approval Program “allow[s] for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need” based on a predicted clinical benefit. One string attached to this program is that companies such as Biogen are required to conduct a Phase IV confirmatory trial to prove the drug’s benefits. The drug remained on the market in the meantime for qualified patients with mild Alzheimer’s disease.
Accelerated approval differs from FDA Emergency Use Authorization (EUA), the latter which was used to produce, approve, and distribute the vaccines for COVID-19. For consumers, one of the most harmful disparities between these two FDA processes is the extent of rigor to which each drug was tested and subsequently received approval.
For example, as exemplified in Biogen’s clinical trials for Aduhelm, there were only approximately 3,500 study participants across Phases I-III of the study. In comparison, the Pfizer COVID-19 vaccine (BNT162b2) study collected data from 43,448 participants across Phases I-III.
Additionally, Aduhelm’s efficacy had been statistically insignificant during Phases I-III. Its first and third studies concluded that “differences from placebo observed in the ADUHELM low dose group numerically favored ADUHELM but were not statistically significant.” Its second study concluded that “No statistically significant differences were observed between the ADUHELM-treated and placebo-treated patients on the primary efficacy endpoint.” In comparison, the Pfizer vaccine had a 95% demonstrated efficacy in preventing the SARS-CoV-2 virus.
What did Aduhelm’s Phase IV Trial Conclude?
Phases I-III based their efficacy on the ability to reduce amyloid beta plaques in the brain—a fundamental pathophysiological characteristic ofAlzheimer’s disease. However, for Phase IV, Biogen presented its findings based on a framework of the efficacy to reduce another protein consistent with the progression of Alzheimer’s, tau.
Based on their data, “levels of the protein [tau] in participants taking Aduhelm dropped by 13-16% from the start of the study, compared to an 8-9% increase among those getting placebo.” Additionally, Biogen concluded that “the gap of not taking the drug didn’t seem to adversely affect the patients.”
This calls their research methods and ethics into question since the framework they used to conclude efficacy between Phases I-III and Phase IV shifted, in addition to their claim that the absence of Aduhelm did not harm patients. For clinic trials, the research and development companies have the burden of proof to ensure that their drug has a significant net-benefit. Furthermore, the Phase IV study for Aduhelm was not placebo-controlled, which makes the analysis of its data more ambiguous.
How Could Aduhelm Potentially Cause Death?
Biogen’s Aduhelm trials had not only prompted skepticism of its efficacy and research methods, but it also raised questions regarding the potential harm caused to Alzheimer’s patients. Among the observed side effects in Phases I-III, the most common include amyloid-related imaging abnormalities (ARIAs)—also known as cerebral edemas and microhemorrhages, which can be harmful to patients with Alzheimer’s disease.
According to the FDA Adverse Event Reporting System (FAERS), “the fatal case came from a 75-year-old female in Canada after she was diagnosed with brain swelling and bleeding, or amyloid-related imaging abnormality (ARIA).” Because its previous studies had shown that an increase in ARIAs is potentially linked to Aduhelm, this may be evidence of causality between Aduhelm and Alzheimer patient deaths.
How Should I Make Sense of This as a Consumer?
Coupled with the recent vote by the European Union to reject the drug entering its pharmaceutical market, and Biogen reporting that it fell almost 98% below analyst sales projections for 2021 Q3, the future of Aduhelm remains uncertain.
As a consumer or patient, it is best to err on the side of caution due to the ongoing developments of this drug. Additionally, if you or a loved one have suffered adverse effects of the Aduhelm (Aducanumab) drug, please be advised that you have legal rights to pursue a claim. At Rheingold, Giuffra, Ruffo & Plotkin LLP, we specialize in medical malpractice, mass tort, personal injury, and product liability cases. We aggressively represent our clients and have recovered billions from companies similar to Biogen. Please contact our office for a free, confidential evaluation of a potential claim. Please call (888) 260 – 0473 to speak with us directly and receive a free consultation.