FDA Approves First Alzheimer's Drug in 20 Years

Alzheimer’s Drug Aducanumab Receives FDA Approval

The US Food and Drug Administration (FDA) approved aducanumab, a drug for Alzheimer’s disease developed by Biogen, on Monday. This decision, following a period of considerable debate within both the scientific and regulatory spheres, marks a significant moment in Alzheimer’s research.

First Novel Treatment in Decades

Aducanumab, to be sold under the brand name Aduhelm, represents the first new Alzheimer’s treatment to gain approval since 2003, as highlighted by the FDA in a recent press release. It is uniquely designed to target one of the hypothesized root causes of Alzheimer’s: the accumulation of beta-amyloid plaques in the brain, which interfere with neuronal communication.

Conditional Approval and Post-Approval Trials

The drug’s approval was granted through the FDA’s ‘Accelerated Approval Program,’ a pathway for early access to treatments for serious conditions. This is utilized when a drug demonstrates effects on a marker of the disease, even if clinical trial results are not conclusive. Consequently, Biogen is obligated to conduct a post-approval confirmatory trial for aducanumab.

The FDA stated, “If the drug does not work as intended, we can take steps to remove it from the market. However, we anticipate further evidence of benefit from the clinical trial and broader use of Aduhelm.”

Early Trial Promise and Subsequent Challenges

Initial trials showed encouraging signs that aducanumab could potentially slow cognitive decline, a key symptom of Alzheimer’s. A 2016 trial, published in Nature, revealed that 125 patients with mild to moderate Alzheimer’s experienced a reduction in plaque levels and some improvement in cognitive function after receiving monthly infusions.

The reduction in brain plaques was described as “robust and unquestionable” in a Lancet Neurology publication. However, the clinical improvements were more subtle, and the extent of cognitive benefit remained unclear.

Phase 3 Trial Controversies

These early results led the FDA to allow aducanumab to bypass phase 2 clinical trials – typically used to determine optimal drug dosages – and proceed directly to phase 3. This decision drew criticism from some medical professionals.

The subsequent phase 3 trials, known as ENGAGE and EMERGE, became a focal point of contention. Both trials involved approximately 1600 patients with early Alzheimer’s receiving monthly intravenous injections. In 2019, both trials were suspended due to a perceived lack of efficacy in slowing cognitive decline.

Further analysis of the EMERGE trial data in late 2019 indicated a 23 percent reduction in cognitive decline compared to a placebo. However, side effects, including brain swelling and inflammation, were observed in around 40 percent of participants. Most of these side effects were mild and resolved within 4-16 weeks.

FDA Advisory Committee Disagreement

Despite the new data, an independent FDA advisory committee did not recommend approval of the drug in November 2020.

FDA Rationale for Approval

On Monday, the FDA justified its approval by emphasizing the drug’s significant impact on beta-amyloid plaques, suggesting that this effect outweighs the risks. Notably, the FDA did not focus on the strength of clinical outcomes; the approval is based on the drug’s ability to target plaques, with cognitive function improvements to be assessed in a follow-up study.

Impact and Market Response

With approximately 6 million Americans living with Alzheimer’s, patient advocacy groups have welcomed the drug’s approval. The Alzheimer’s Association has characterized it as a “victory for people living with Alzheimer’s.”

Prior to the FDA’s decision, it was anticipated that aducanumab, if approved, would become a “blockbuster drug.” The financial markets appear to support this expectation.

Biogen’s stock price surged 40 percent following the announcement, after a temporary trading halt. Eisai Co. Ltd, a Japanese company collaborating with Biogen, saw its shares increase by over 46 percent in the first three hours after the FDA’s approval.

Pricing and Future Outlook

Biogen has been strategically preparing for this approval, with approximately 600 sites ready to launch the treatment. The company has also submitted marketing applications in Brazil, Canada, Switzerland, and Australia. A year’s supply of the drug is priced at $56,000, as announced on June 7.

Implications for Future Research

This approval may encourage other pharmaceutical companies to pursue similar beta-amyloid-targeting therapies. Eric Reiman, executive director of Banner Alzheimer’s Institute, previously stated that confirming the effectiveness of beta-amyloid treatment in slowing cognitive decline would be a “game changer.”

The aducanumab trials are seen as a crucial test of this hypothesis. Howard Filit, founding executive director of the Alzheimer’s Drug Discovery Foundation, described aducanumab as “the first rigorous test of the beta-amyloid hypothesis.”

At least one other beta-amyloid targeted drug from Eli Lilly is currently in clinical trials, and further developments are anticipated, contingent on the results of Biogen’s confirmatory study.