FDA pulls breakthrough status from Trevena’s pain drug

Trevena has lost its breakthrough designation for pain treatment oliceridine, just a few months after the FDA rejected its marketing application for the drug.

In an SEC filing, Trevena said that the regulator took the decision after reviewing the phase 3 results with the mu opioid receptor-targeting drug and concluding that “under the conditions studied, these data were not sufficient to support the continuation of FDA’s previously granted breakthrough therapy designation.”

Last November, Trevena was hit hard by the FDA’s decision not to approve oliceridine for moderate to severe pain, despite the company’s arguments that the drug reduces the risk of respiratory and gastrointestinal side effects seen with other painkillers—the profile that underpinned the FDA’s BTD.

As it turned out, the agency said Trevena had not submitted adequate safety data to support its proposed dosing, and it said the drug had abuse and overdose potential similar to other opioid drugs. It also asked for additional clinical data on QT prolongation, a marker that can indicate underlying cardiovascular risk.

On the plus side for Trevena, it now seems the FDA has agreed that its safety database will support a refile for oliceridine, at a maximum daily dose of 27mg, providing it completes a phase 1 study in healthy volunteers that gives the all-clear on the QT interval question.

That should get underway in the next few weeks, according to the company, which also maintains that the loss of the BTD will not “impact the timing of FDA’s review of the oliceridine new drug application following resubmission.”

Losing a BTD is a pretty rare event, although there have been other examples. Last year, Synthetic Biologics withdrew its BTD for ribaxamase after an FDA review found an imbalance in patient deaths in a phase 2b trial of the drug.

Anonymized data (PDF) from the FDA’s Center for Drug Evaluation and Research (CDER) shows that in 2018, two BTDs were withdrawn after being granted with another four rescinded, compared to two and three respectively the previous year.

The number of BTDs requested and awarded by the FDA has increased in the last couple of years under outgoing Commissioner Scott Gottlieb, reaching a peak in 2018 with 136 filed, 59 granted and 60 denied.

Given Gottlieb’s industry-friendly stance and willingness to embrace measures to speed access to new therapies, it will be interesting to see the trend under the next commissioner, whoever that will be.