FDA's Project Optimus Drives Increased Dose Optimization in Early Trials
Deepak Bhamidipati, MD, discusses the impact of the FDA's Project Optimus on early-phase drug development protocols.
Deepak Bhamidipati, MD, assistant director, drug development, Sarah Cannon Research Institute (SCRI), discusses the impact of the FDA's Project Optimus on early-phase drug development protocols.
Here, he highlights a significant increase in the implementation of dose optimization plans from less than 20% of protocols in 2021 to the vast majority in 2024, following the announcement and finalization of FDA guidance.
“A key takeaway from our study [was] that between 2021 when this FDA Project Optimus was announced, to 2024 when the FDA guidance was finalized, there was a significant increase in the implementation of a dose optimization plan within these early-phase protocols,” he explains. “So, less than 20% of protocols were mentioning anything about dose optimization in 2021 but in 2024, it is the vast majority of protocols that are actually including a plan.”
This shift means that more studies are evaluating multiple doses in the dose expansion phase before moving to phase 2 or 3 trials. Bhamidipati emphasizes the importance of finding the optimal dose, not just the maximum-tolerated dose, to ensure that therapies are applicable and well-tolerated by a broader range of patients in the community, who may differ from typical clinical trial participants.
“I think this highlights that the FDA and the drug development community in general has taken this issue seriously,” he adds.
In addition, Bhamidipati points out that the increased use of "backfill" cohorts, which allow enrolling patients into previously evaluated dose levels, is crucial for gathering more comprehensive safety and efficacy data with a larger number of patients in the early stages, ultimately aiding in the identification of the most appropriate dose for further development and FDA approval.
“This is about gathering more information, because I think with just a handful of patients that you typically see in a dose escalation study, you are really not getting a whole lot of information about how these patients are truly tolerating a given drug and even with respect to how well the drug is working. If you only have a handful of patients, it can be difficult to tell. I do think the increased implementation of backfill cohorts is very important, and certainly in line with trying to get as much information as possible to find the right dose that moves forward for FDA approval.”
