Despite the lack of a randomized controlled trial for US WorldMeds’ investigational drug, an FDA advisory committee found that the company provided adequate data to support its benefit in high-risk neuroblastoma.
Pictured: Four people with their thumbs up in approval/iStock, PeopleImages
The FDA’s Oncologic Drugs Advisory Committee on Wednesday voted in favor of US WorldMeds’ investigational drug eflornithine hydrochloride (DFMO) for the reduction of relapse risk in pediatric patients with high-risk neuroblastoma.
In a 14-6 vote, the panel of external experts found that even without a randomized controlled trial (RCT), US WorldMeds had provided enough evidence to conclude that DFMO boosts event-free survival in its target patient population.
“I believe that the data for event-free survival is compelling,” Christopher Lieu, committee chairperson and director of the Gastrointestinal Medical Oncology Program at the University of Colorado, said during the meeting. Lieu voted yes, but also noted that the lack of randomization likely could have overestimated the benefit of DFMO in the data presented during the session.
“Having said that, this is a therapeutic that has relatively lower toxicity compared to what we typically discuss,” Lieu said in explaining his vote. “I believe that the expected benefits outweigh the risks of treatment.”
Still, in his summary of the panel’s votes and rationales, Lieu pointed to worries that this might lead to a “slippery slope” in terms of the degree of clinical evidence that will be required of future drug applications in similar rare and difficult-to-study indications. The panelists who voted against DFMO raised similar concerns.
“There is a lot of concern from the group about what the future holds for drug development and what level of evidence the FDA will require in similar situations in the future,” Lieu said.
In its application for DFMO, US WorldMeds provided data from a prospective Phase II, multicenter, open-label, single-arm study of DFMO maintenance treatment in patients who had completed multiagent and multimodality therapy.
In a briefing document posted ahead of the adcomm meeting, US WorldMeds said that they had been told by the FDA that an RCT is the “preferred path to registration” for these types of drugs. However, given the challenges of conducting a randomized study in rare diseases, the company instead proposed an external control approach.
The company then drew from a retrospective chart review of patients with high-risk neuroblastoma and also worked collaboratively with the FDA to design a “rigorous propensity score matched analysis” using a landmark study as its external control.
In its own briefing document, the FDA noted that US WorldMed’s use of an external control in this situation is “reasonable” but also conceded that there are “inherent limitations” associated with externally controlled data, such as interpreting the estimated treatment effect of an investigational intervention.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
