The US Food and Drug Administration (FDA) has declined to approve the intravenous (IV) opioid oliceridine (Trevena Inc) for the management of moderate to severe acute pain in adults who require an IV opioid.
The Anesthetic and Analgesic Drug Products Advisory Committee narrowly voted against approving oliceridine in October, as reported by Medscape Medical News.
“Consistent with the discussion at the recent Advisory Committee meeting, FDA has requested additional clinical data on QT prolongation and indicated that the submitted safety database is not of adequate size for the proposed dosing. FDA also requested certain additional nonclinical data and validation reports,” the manufacturer said in a news release.
The company said it plans to meet with the FDA soon to develop a path forward for oliceridine.
Oliceridine is a μ-opioid receptor modulator designed to provide analgesia as effectively as morphine with faster onset of action, less respiratory depression, less slowing of gastrointestinal motility, and less sedation compared with morphine. Its onset of action is within 5 minutes, and effects last 1 to 3 hours.
The drug‘s clinical development program included three phase 3 studies in patients after abdominal or bunion surgery, as well as other medical and surgical patients. The drug was compared with placebo and IV morphine.
In the second study, the 0.35- and 0.5-mg doses of oliceridine led to a statistically significant reduction in pain intensity compared to placebo, but the 0.1-mg dose did not. The third study showed that morphine provided greater reduction in pain intensity than the 0.1-mg and 0.35-mg doses of oliceridine, which was statistically significant.
According to the FDA, none of the oliceridine treatment arms experienced a significant reduction in the expected cumulative duration of respiratory safety events compared to morphine. There were trends toward decreased respiratory events with oliceridine relative to morphine for some safety parameters, although this was not consistent across all parameters, the FDA concluded.
“The problem with this drug is that it’s not a substantial improvement over what we have now,” commented Raeford Brown Jr, MD, from University of Kentucky, Lexington, who chaired the advisory committee meeting on oliceridine.
Brown called oliceridine “a disappointment” and said he was “surprised” that the advisory committee vote on oliceridine was so narrow.
In the news release, Mark Demitrack, MD, Trevena senior vice president and chief medical officer, said, “Developing a novel chemical entity is complex, and we believe the data we have to support oliceridine advances the pharmacology of acute pain therapeutics. We were encouraged by the discussion at the Advisory Committee meeting and look forward to continuing a productive dialogue with FDA.”