Promising cancer drugs that are fast-tracked through approvals don’t always deliver expected outcomes. A recent study revealed that approximately 40 per cent of anti-cancer treatments approved via the US Food and Drug Administration’s (FDA) accelerated approvals pathway between 2013 and 2017 failed to demonstrate clinical benefits in follow-up trials conducted over more than five years.
Originating from the urgent need during the HIV/AIDS epidemic in the 1980s and early 1990s, the FDA’s accelerated approvals program has facilitated the early approval of drugs for serious conditions that lack existing treatments since 1992. Accelerated approvals are particularly prevalent for cancer therapies, with one-third of all oncology drug approvals taking this route. Remarkably, over 80 per cent of all accelerated approvals are granted to cancer therapies.
These approvals often depend on surrogate markers of drug effectiveness, which are expected to predict actual clinical benefits. For instance, cholesterol levels serve as a surrogate marker for heart disease risk, yet companies must demonstrate in post-approval trials that their drugs can actually prevent death from heart disease. In cancer research, the ultimate goal is often to demonstrate improved overall survival. However, many trials rely on progression-free survival as a surrogate measure, indicating the duration a patient lives before the cancer worsens.
Research from Brigham and Women’s Hospital in Boston has extended previous analyses of this program, which has faced criticism for its lower regulatory standards and the approval of expensive drugs with dubious benefits. “Although accelerated approval can be useful, some cancer drugs do not end up demonstrating benefit in extending patients’ lives or improving their quality of life,” noted epidemiologist Ian Liu and his colleagues in their study.
From 2013 to 2023, 59 cancer drugs were granted provisional approval through this pathway, covering 129 different uses. For the 46 drug indications approved between 2013 and 2017, results from confirmatory trials were still pending for seven medicines by mid-2023, and 10 had been withdrawn. Unfortunately, 41 per cent – or 19 out of 46 cancer drugs approved during that period – failed to extend patients’ lives or enhance their quality of life. Including the seven ongoing trials, this percentage increases to 57 per cent of fast-tracked cancer drugs showing no benefit five years after approval.
There are indications of system improvements, as drugs proven ineffective in follow-up trials have been withdrawn from the market more rapidly, decreasing from about 10 years in 2013 to only 3.6 years in 2017. Yet, pharmaceutical companies are taking longer to prove drug effectiveness in mandatory post-approval studies, allowing drugs to remain on the market for years before it’s clear whether surrogate markers truly reflect clinical benefits.
The duration for fast-tracked drugs to receive traditional approval, assuming they demonstrate benefit, has increased from 1.6 years to 3.6 years over the study period. This issue parallels findings from other studies indicating delays in confirmatory trials, leading to prolonged use of some drugs for over a decade without verified patient benefits.
Another significant concern in clinical cancer research was highlighted in a 2022 study, which found that data from more than half of 300 audited clinical trials from the last decade remained unavailable, despite those trials supporting FDA drug approvals. Despite ongoing critiques, accelerated approvals faced intensified scrutiny following the FDA’s controversial 2021 decision to approve aducanumab for Alzheimer’s disease, which was later discontinued by its manufacturer, Biogen, due to shifting priorities.
In response to these challenges, the US government enacted legislative reforms to the accelerated approval pathway in June 2022, which were described as “long overdue”. These reforms mandate that drug companies must have begun confirmatory trials prior to receiving accelerated approval and report their progress biannually.
The effectiveness of these reforms remains to be seen. The study has been published in the Journal of the American Medical Association.
