The Fast and Furious of the Pharmaceutical Industry: Tragedy and Reflection on Accelerated Approval of Drugs

An amyotrophic lateral sclerosis (ALS) drug with annual sales of $400 million has been mockingly likened by industry analysts to "its efficacy is not as cool as mints". And another blood cancer treatment drug with sales approaching $850 million was not only forced to withdraw from the market due to a lack of conclusive efficacy, but also due to safety risks in the early years, resulting in the unfortunate death of patients. These are just two examples of the many tragedies of ineffective drugs in medicine. According to relevant reports, since 2014, the accelerated approval of drugs that failed to pass confirmatory studies after the market, and the drugs that left the market in the United States, the cumulative global sales have reached at least $3.6 billion. Gregg Gonsalves, a distinguished professor of public health at Yale University, puts it bluntly: "We have faster access to drugs, but less understanding of them, and higher costs for patients."

To get treatments to patients faster, pharmaceutical companies have adopted strategies such as "priority review," "fast track," "accelerated approval," and "breakthrough therapy" designation. In addition, for those projects that do not directly meet the above conditions, there is the "magic tool" of priority review vouchers, which seems to make it jump from the country field to the palace in an instant. According to Bloomberg's in-depth data analysis, most new drugs in the United States gained market entry through one or more of these accelerated pathways, and this trend is particularly significant in 2023, when two-thirds of new drugs were successfully launched in this way.

To be sure, the intention of pushing drugs to market quickly is undoubtedly positive, but the key is how to screen and support those drugs that are truly valuable. Just as a "let some people get rich first" policy needs to clearly define the beneficiaries, should it support those who are opportunistic, or the pioneers who can really promote social progress? The FDA's huge fast-track approval system is inevitably mixed with the phenomenon of confusion. When the accumulation of problems begins to erode the purpose of the policy, we have to ask: have we reached a turning point?

Amylyx Pharmaceuticals Inc. 's ALS treatment Relyvrio sought FDA approval in 2022 based on a small trial that tended to show no significant clinical benefit. The FDA's expert advisory panel was initially negative, but then dramatically reversed course and recommended expedited approval. Behind this shift was a confluence of factors: strong advocacy and pressure from the ALS patient community, and Amylyx's firm commitment to take the initiative to delist if post-market confirmatory studies were not up to standard. Amylyx's share price soared more than 50% after the accelerated approval, and the company put a whopping $158,000 price tag on the drug, which is made up of two simple small molecules, and achieved $300 million in sales by 2023. However, with the failure of the Phase III study PHOENIX, Relyvrio's glory was short-lived, and Amylyx had to take it off the market, lay off 70% of its staff, and its share price plummeted by more than 80%.

In general, the FDA closely follows the principle of sufficient evidence when approving drugs, ensuring that the effectiveness of the drug and its benefits far outweigh the potential risks. However, the accelerated approval mechanism has gradually evolved from its initial marginal role to the mainstream trend, which is undoubtedly a break with the traditional FDA approval practice. Pressure from patient groups and their advocates, through nonprofit organizations and other channels, may be behind this discrepancy in standards. The ALS Association, for example, proudly claims in its annual report that it "led a campaign to urge the FDA to take urgent and flexible action" to accelerate the rollout of Amylyx. Even after the failure of Relyvrio's Phase III study, the ALS Association issued a statement expressing support for the early approval, emphasizing Relyvrio's safety and patients' willingness to take risks even in the face of ineffective results.