Dive Brief:

• Going forward, the Food and Drug Administration will generally only require one pivotal trial to support the approval of new medicines, top agency officials announced Wednesday.
• Writing in the New England Journal of Medicine, FDA Commissioner Marty Makary and top deputy Vinay Prasad said they are ending the “two-trial dogma,” a standard set in the 1960s to ensure the safety and efficacy of medical products. Technological advancements mean the FDA and sponsors can now focus on designing one high-quality trial that can better assess results, they said.
• In practice, many drugs in recent years have sped to market with only one pivotal study, thanks to changes Congress made in 1997. But Makary and Prasad argued that a new official standard is needed. “Default options anchor individuals and institutions psychologically, and we believe that formally articulating the FDA’s new position will spur biomedical innovation,” they wrote.

Dive Insight:

The new position is the latest from an agency that has pledged to speed up drug reviews yet thrown curveballs at the industry time and again during President Trump’s second term. Shifting guidance, delays and surprise rejections have left company officials wary of unpredictable regulators as they undertake the already risky task of developing new medical products.

Just in recent days, the FDA reversed course and said it would consider Moderna’s new flu vaccine after shocking the industry by refusing to review it. Prasad, the head of the Centers for Biologics Evaluation and Research, reportedly overruled career staff in issuing the rejection. Within days, Trump hauled Makary in for a White House meeting to discuss the FDA’s handling of vaccines, Politico reported.

Now, Makary and Prasad say they are offering the industry more predictability and a chance to save money, which can be passed onto consumers. “Lowering capital costs for drug developers may remove a persistent argument in justification of lofty and rising drug prices for everyday Americans — the onerous cost of research and development,” they said.

At the heart of the officials’ argument is that times and technology have changed. In the 1960s, the two-trial standard in the last phase of development was designed to avoid a sponsor succeeding by chance. Statistically, two pivotal trials dramatically reduced the possibility of an error in finding a medication safe and effective, simply because “one must be lucky twice,” they said.

“Yet modern drug development establishes credibility in multiple ways, relying on both statistical and biologic inferences,” they said. “Two trials should be seen as just one of many interlocking facets of clinical credibility and in 2026 there are powerful alternative ways to feel assured that our products help people live longer or better than requiring manufacturers to test them yet again.”

Makary and Prasad emphasized that the FDA may at times still require two studies and the change will roll out as the agency amps up an initiative to collect postmarketing data. The new standard is also building on the accelerated approval model that has been increasingly used by drugmakers in recent years, allowing clearance based on one pivotal trial and for confirmatory evidence to be generated afterwards.

Indeed, in 2020, more than half of the 49 new medicines that came to market did so with just one pivotal trial, according to an analysis published in 2022. Still, the move could raise concerns about safety and efficacy. Under the Biden administration, the FDA had taken a tougher stance on accelerated approvals and faced broad criticism about the process.

In the past, the accelerated approval model largely favored new medicines for cancer, rare diseases and those with a high unmet need. The new standard, according to Jefferies analyst Andrew Tsai, could help companies working on drugs in the areas of ophthalmology, psychiatry, immunology and cardiology among others.

It’s unclear how the policy will impact drugmakers that already have one pivotal trial done and another pending, Tsai wrote in a note to clients. And while it will likely mean that companies ensure any single study in the future is “high quality,” the one-trial model may actually pose more risk for some developers, he added.