The FDA’s reported plan to move toward single-trial approvals has stirred industry concern, but one group of analysts views the proposal as a catalyst for greater R&D investment in the sector.
Earlier this week, FDA Commissioner Marty Makary, M.D., told Stat that the agency plans to shift to a default of requiring only one pivotal clinical trial for most medical product approvals.
Currently, many areas already run on this standard, while some indications and modalities require two or more trials.
“You can achieve the same statistical power with one trial as you would with two trials when it’s designed and controlled appropriately,” Makary reportedly told Stat.
The agency said it would publish a press release on the guidance soon, according to Stat.
As of publication, the Department of Health and Human Services has not responded to Fierce’s request for additional information about the potential guidance.
While this report has triggered both confusion and alarm across the industry, analysts at Jefferies believe the shift actually carries advantages.
“We think the market's thinking is backwards that defaulting to a single pivotal trial for approvals is a risk,” the analysts wrote in a Dec. 4 note.
As an example of the concerns raised by the report, a separate team of analysts at Leerink wrote that the change could “shrink the pool of work CROs have, which would be a clear negative.” The Leerink analysts cautioned that much remains unknown about the potential policy shift.
While the Jefferies team received feedback in line with that concern, they said the change could drive efficiency and ultimately prompt the industry to expand its horizons.
“At the highest level, if we assume success rates are unaffected, we think a reduction of time (FDA's aim) and cost in development increases R&D ROI and INCREASES investment in R&D," they wrote.
The Jefferies team cited a 2024 AgencyIQ analysis that found about 60% of new molecular entity approvals from 2020 to 2023 were based on one pivotal trial. On the other end of the spectrum, approvals requiring three or more pivotal trials made up only 5% of decisions, with most of those approvals using orphan designation and priority review pathways.
Furthermore, these single-trial approvals are already occurring at high rates in therapeutic areas where the sector invests the most. Sixty percent of oncology approvals from 2011 to 2019 were already based off single pivotal trials.
This is important given the fact that oncology has been the sector’s largest area for therapeutic R&D investment for nearly two decades, with oncology accounting for more than 40% of the industry’s pipeline programs in the 2020s, according to AgencyIQ.
In the last five years, approvals from single pivotal trials have become more common not only in oncology, but across neurology, cardiovascular, hematology, endocrinology and nephrology—some of the next largest investment areas.
All this data builds Jefferies’ argument: the FDA change could help boost return on investment and therefore drive R&D spend.
“Pharma is not developing all it would like to,” the firm wrote. “If regulatory change improves the likelihood of ‘regulatory and technical success’ or lowers the time and cost to get there, more should be developed to climb out of the industry’s stagnation.”
The move is also likely not an abrupt decision, but instead a trend that has been in the making for years.
“Sponsors would have already been having pre-phase 3 discussions with the regulator on the appropriateness of a single pivotal [trial],” the Jefferies team wrote.