FDA's Califf backs limited use of single-arm trials, but says regulatory pathways for some cancers should 'move into a new phase'

The biotech industry has been resistant to a policy reform that would limit single-arm trials for drug approvals and it appears that even FDA Commissioner Robert Califf, M.D., thinks they're necessary in some circumstances. 

But Califf, in a briefing with reporters Thursday, backed proposals by the agency's cancer czar to limit single-arm trials to nab accelerated approvals. He said that while the pathway remains valuable for certain kinds of cancers, diseases with existing treatments should take a more "mainstream" regulatory route. Single-arm trials involve only dosing the treatment, rather than an additional control arm, requiring fewer patients in the trials, which subsequently makes them cheaper and easier to run. 

Since taking the helm at the FDA, Califf and other top officials have been clear about efforts to reform the accelerated approval pathway. Califf has personally advocated for expediting follow-up trials so that they begin before approval and the agency’s cancer czar, Richard Pazdur, has proposed limiting the use of single-arm trials. 

Naturally, the considerations have irked top leaders in biopharma, namely Paul Hastings, CEO of Nkarta Therapeutics and chairman of the industry trade group BIO. In an interview last month he contended the reforms risked innovation and the speed at which new drugs could reach patients. 

Califf did not directly address criticism from the industry in his Thursday remarks but backed Pazdur’s proposal, and Pazdur himself. In terms of single-arm trials, he said in some cases, like rare disease, it makes sense. But in other areas, where there’s already an effective treatment, “I think you have a very different situation.”

“The more diseases for which we have some treatment, the more sense it makes to act more like mainstream where you do proper control, randomized trials and make sure you get a definitive answer,” he said. 

He also noted that there are “thousands” of rare diseases with no effective treatment in addition to chronic diseases for which, “we have amazingly promising opportunities where accelerated pathways make sense as long as we can get the answer quickly in the post-market phase.” 

The pathway was launched in the early 90s to help invigorate development of treatments for HIV but in the last decade or so has been primarily used by companies developing cancer drugs. One report found that from 2010 to 2020, 85% of accelerated approvals were for oncology indications. 

When asked whether or not he thought that at this point, the pathway could be better utilized for therapeutic areas other than oncology, Califf said no, and that use in cancer was still right. He added that thanks in large part to Pazdur’s work, the life expectancy of cancer patients has been increasing, not decreasing. According to the American Cancer Society, the risk of dying from cancer has fallen by 32% from 1991 to 2019.

“Now cancer, in many cases, needs to move into a new phase because there are effective treatments for many kinds of cancer,” he said. Califf noted that there remain many kinds of cancers without treatments, underscoring his larger point that each case presented using the accelerated approval pathway requires individual consideration.