8:44 AM
 | 
Oct 09, 2018
 |  BC Extra  |  Company News

FDA reviewers doubt benefits of Trevena's analgesic over morphine

Trevena Inc. (NASDAQ:TRVN) was off $1.91 (64%) to $1.07 on Tuesday after FDA reviewers expressed doubts that the company’s Olinvo oliceridine (TRV130) offered a benefit over morphine, according to briefing documents released ahead of a planned advisory committee meeting.

In "the most clinically relevant" efficacy analysis of two Phase III studies, the reviewers wrote, morphine led to significantly greater reductions in pain intensity than both doses of Olinvo for which Trevena is seeking approval. The reviewers wrote that FDA "did not agree with Trevena's proposed endpoint" intended to show Olinvo's superiority to morphine with regard to respiratory safety burden "due to concerns with its clinical meaningfulness." They wrote that none of the studies' Olinvo treatment arms showed a significant reduction in the expected cumulative duration of respiratory safety events compared with morphine.

"A conclusion of benefit in a dose-related safety outcome cannot be made without a demonstration of similar efficacy," the reviewers wrote.

The agency's Anesthetic and Analgesic Drug Products Advisory Committee is to meet Thursday to discuss Trevena's NDA for Olinvo, a G protein-biased μ opioid receptor (MOR; OPRM1) ligand, to treat moderate-to-severe pain in adult patients for whom an IV opioid is warranted. The therapy is designed to stimulate G protein-coupling with reduced β-arrestin recruitment compared with conventional opioids, which Trevena believes could lead to less respiratory depression, gastrointestinal motility issues and sedation compared with morphine, according to FDA's briefing document.

The reviewers did note that in one study's lowest dose group, a significantly smaller proportion of patients receiving Olinvo had respiratory safety events compared with the morphine group, but the reviewers did not find the safety outcome clinically relevant because that Olinvo dose provided less analgesia than morphine.

FDA's document also said Olinvo has "an abuse potential, overdose potential and ability to produce physical dependence that is similar to other μ opioid agonists." Concerning its mechanism, the reviewers wrote that "it does not appear that the biased agonism of oliceridine with regard to preferential recruitment of G-protein over β-arrestin2 translates into a human safety advantage for oliceridine compared to traditional μ opioid agonists."

The therapy's PDUFA date is Nov. 2; it has breakthrough therapy designation from FDA.

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