Study: FDA’s expedited programs play increasing role in bringing novel drugs to market

Expedited development and review programs established by the US Food and Drug Administration (FDA) have a growing role in bringing drugs and biologics to market, with novel orphan and nonorphan products using expedited programs alone in combination to achieve FDA approval more frequently over the last 13 years, according to recent research published in JAMA Network Open.

“In this study, use of expedited programs alone and in combination for novel drug development and approval was common among orphan and nonorphan drug products and increased over time, highlighting the integral roles of these programs in bringing novel drugs to market,” Andrea N. Monge, MD, PhD, with the Office of the Commissioner at FDA, and colleagues wrote in their study.

Monge and colleagues examined 581 FDA-approved pairs of novel drugs and their indications in a cross-sectional study approved between January 2008 and December 2021, evaluating how and through what combinations of the accelerated approval, breakthrough therapy, fast track and priority review programs established by the FDA the drugs and biologics came to market. The researchers studied orphan and nonorphan novel drugs, therapeutic biologics, and small-molecule drugs that were first in class, and/or first approved in the United States as well as if they used programs alone or in combination for approval. They also categorized drugs by therapeutic area and whether they were used for treatment or diagnostic medical imaging.

Of the drug-indication pairs studied, there were 442 small-molecule drugs (76.1%), 252 orphan drugs (43.4%) and 139 therapeutic biologics (23.9%). Monge and colleagues found that 41 of 55 drug-indication pairs (74.5%) in 2021 used one or more expedited program compared with 11 of 26 drug-indication pairs (42.3%) in 2008.

Within the 363 overall drug-indication pairs using one or more expedited program, there were 225 orphan drugs (62.0%), 97 biologic drugs (69.8%) and 226 small-molecule drugs (60.2%). The accelerated approval program was used by 82 of 581 novel drug-indication pairs (14.1%), with 65 drugs in oncology (79.3%) and 70 drugs having an orphan designation (85.4%).

“Our findings highlight the central role of expedited programs in affording patients with unmet medical needs timely access to orphan drugs,” the researchers wrote.

Monge and colleagues noted a four-fold increase in the use of drugs receiving an orphan drug designation over the last three decades and said the trend if using expedited programs will likely continue over time, particularly for oncology drugs. “With an increase in more conditions for narrowly defined patient populations, it appears likely that use of expedited programs such as Accelerated Approval by orphan drugs will increase,” they said.

The authors also observed that approved biologics used expedited programs more often than small-molecule drugs, even as biologics are “generally technologically innovative, structurally complex products derived from either human, animal, or microorganism living material” compared with small-molecule drugs.

“Although the objective of the expedited review programs is not to facilitate medical innovation, the programs may indirectly provide an avenue for advanced treatment technologies to reach patients,” Monge and colleagues wrote.

While the authors noted the controversy surrounding confirmatory trials for accelerated approval drugs, they acknowledged the tension that exists with establishing standards of evidence required to achieve FDA approval in the program relative to the speed of conducting confirmatory trials to establish clinical benefit. Monge and colleagues said analyzing this relationship was not within the scope of their study, but “need[s] to be further understood to ensure that any changes to these programs continue to afford patient access to life-saving drugs with appropriate safeguards.” (RELATED: OIG raises concerns about accelerated approval pathway, Regulatory Focus 30 September 2022)

JAMA Netw Open Monge et al.

Study: FDA’s expedited programs play increasing role in bringing novel drugs to market

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