Policy shift favors one pivotal trial, aiming to cut costs, speed access and reshape how therapies for aging reach patients.
For many years, the drug approval process in the US followed a rhythm. Prove it works once, then prove it again. Two large clinical trials became the gold standard, a regulatory habit dating back to the early 1960s, when biology was murkier, tools were blunt and regulators worried that a single positive result could simply be a fluke.
Last week, that long-standing default quietly ended. In a commentary published in the New England Journal of Medicine, leaders of the Food and Drug Administration (FDA) announced that going forward, one pivotal clinical trial – not two – should generally be enough to support approval of new medicines [1].
FDA Commissioner Marty Makary and his deputy Vinay Prasad called it an end to what they described as the “two-trial dogma.” The reasoning is simple: medicine has changed, and regulation should catch up.
Why one trial is now considered enough? The original logic behind requiring two trials was statistical caution. If a drug worked twice, it was less likely that success was due to chance. As Makary and Prasad put it, “one must be lucky twice.” But modern drug development, they argue, rarely relies on blind luck.
Today’s therapies are typically built on years of biological insight, supported by biomarkers, genetic evidence and sophisticated trial designs. In that context, running the same expensive experiment twice may add more cost than clarity.
“Default options anchor individuals and institutions psychologically,” Makary and Prasad wrote, adding that formally changing the default could “spur biomedical innovation.” In other words, when the rulebook signals flexibility, companies design differently from the start [2].
Importantly, this is not a free-for-all. The FDA can still require two trials when uncertainty remains. The shift is about emphasis. Fewer boxes to tick, more attention paid to whether a single study is rigorous, well-controlled and biologically convincing.
The announcement also arrives at a tense moment for the agency’s relationship with industry. Under Trump’s second term, drug developers have faced shifting guidance, surprise rejections and sudden reversals – including the recent episode where the FDA initially declined to review Moderna’s new flu vaccine, only to reverse course days later.
Against that backdrop, Makary and Prasad framed the new policy as an attempt to restore predictability. Fewer required trials mean lower development costs and shorter timelines, savings they argue could weaken the industry’s most persistent defense of high drug prices: the sheer expense of research and development.
“Lowering capital costs for drug developers may remove a persistent argument in justification of lofty and rising drug prices,” they wrote.
Implications for longevity science
This shift could be quietly transformative. Aging-related therapies often struggle under traditional approval models. Aging itself is not classified as a disease, and interventions tend to target slow, complex biological processes rather than dramatic short-term outcomes. Requiring two massive late-stage trials has historically discouraged investment, especially for drugs aimed at prevention or healthspan extension rather than acute illness.
A one-trial default lowers that barrier. It creates more room for therapies supported by strong biomarkers – inflammation, metabolic health, immune resilience – even if long-term outcomes like lifespan take years to measure. It also aligns with the FDA’s growing interest in postmarketing data, where real-world evidence continues to accumulate after approval rather than delaying access upfront. In that sense, the policy goes from certainty before access. To learning while deploying carefully.
Still, the change will raise eyebrows. Critics worry that fewer trials could mean weaker evidence and higher safety risks. The FDA itself acknowledges the concern, noting that two poorly designed trials offer no real protection, while one high-quality study may be more informative.
The risk may also shift onto developers. With only one pivotal trial, there is less room for error. A flawed design, weak endpoint or ambiguous result could sink a program outright.
More than a technical tweak, this is a signal about how the FDA sees the future of medicine. The agency is betting that better science, smarter trials and ongoing data collection can replace redundancy without sacrificing rigor.
For longevity research, long accused of being too slow, too expensive or too speculative, that signals a regulatory climate more willing to meet aging science where it is, rather than forcing it into frameworks built for another era. Whether this accelerates a wave of credible longevity therapies remains to be seen. But for an industry often stalled at the gate, the door just opened a little wider.
[1] https://www.nejm.org/doi/10.1056/NEJMsb2517623
[2] https://www.biopharmadive.com/news/fda-makary-prasad0one-pivotal-trial-nejm/812557/
