Mixed results have been reported from two pivotal, phase 3 studies of the opioid painkiller oliceridine (Olinvo, Trevena, Inc.) in subjects with moderate-to-severe acute pain after bunionectomy or abdominoplasty. In both studies, all dose regimens achieved their primary endpoint of statistically greater analgesic efficacy compared with placebo, as measured by the responder rate. However, only two of the three doses were found to be as effective as morphine. Moreover, while oliceridine induced lower rates of nausea and vomiting and lower rates of depressed breathing, only one dose achieved a statistically significant effect.
APOLLO-1 and APOLLO-2 were multicenter, randomized, double-blind, placebo- and active-controlled trials. The primary objective of each study was to evaluate the analgesic efficacy of oliceridine compared with that of placebo. Secondary endpoints included comparisons of the efficacy, safety, and tolerability of oliceridine and morphine. Both studies included measurements of nausea and vomiting, which occur in approximately 30% of postoperative patients, as well as measurements of respiratory safety.
In the APOLLO-1 (bunionectomy) trial, all three oliceridine regimens (0.1 mg, 0.35 mg, and 0.5 mg) achieved the primary endpoint with statistically superior responder rates compared with placebo at 48 hours (P < 0.0001). However, only the 0.35-mg and 0.5-mg oliceridine doses demonstrated efficacy comparable with that of morphine at 48 hours, based on the responder rate (both doses P < 0.005 for noninferiority to morphine).
The results were similar in the APOLLO-2 (abdominoplasty) trial. All three oliceridine dose regimens achieved the primary endpoint with statistically superior responder rates compared with placebo (adjusted P < 0.05 for the 0.1-mg regimen; adjusted P < 0.001 for the 0.35-mg and 0.5-mg regimens). But only the 0.35-mg regimen demonstrated efficacy that was significantly noninferior to that of morphine at 24 hours (P < 0.05).
Trevena intends to submit a marketing application for oliceridine to the FDA in the fourth quarter of this year.