- Shares in Pennsylvania biotech Trevena slumped by more than 60% in value Tuesday morning, after documents released by the Food and Drug Administration raised a number of concerns about the company's lead drug candidate.
- The drug, called oliceridine, is an intravenous opioid designed to treat moderate to severe acute pain. An FDA advisory panel is set to meet Thursday to review clinical results Trevena submitted to the agency in support of an application for approval.
- Trevena has pitched oliceridine as safer than currently available intravenous opioids, pointing to the drug's mechanism of action as a key differentiating factor. Briefing documents from the FDA, however, reveal the agency had not agreed to Trevena's plans to measure oliceridine's impact on respiratory safety burden.
Investors typically pore over FDA briefing documents, which are published by the agency two days before advisory committee meetings. Staffed by experts, the panels make recommendations to the FDA for or against approval of certain experimental drugs.
Sometimes these documents offer few new insights into the agency's thinking on a particular drug. In this case, it was clear FDA staff had several concerns about Trevena's trial design and results.
For its New Drug Application for oliceridine, Trevena submitted results from three Phase 3 studies — two randomized and one conducted open-label. In both of these trials, the two higher tested doses of oliceridine showed a statistically greater reduction in pain intensity than placebo. (Comparisons versus morphine on this measure were more mixed.)
But key to Trevena's case is the company's claim that oliceridine's more selective mechanism of action makes it safer than conventional opioids, with less respiratory depression and nausea.
On this point, it turns out, the FDA never agreed to Trevena's plans for measuring the superiority of oliceridine to morphine in terms of respiratory safety burden. Further, in both randomized studies, Trevena's drug did not demonstrate a significant lowering in the expected cumulative duration of respiratory safety events versus morphine, FDA staff wrote.
The agency acknowledged that trends did support a decreased percentage of respiratory events with oliceridine versus morphine but only on "some parameters."
Respiratory safety burden wasn't the only thing the FDA saw differently than Trevena, either. The documents disclosed the agency had a number of disagreements with the biotech in an April 2016 meeting and a November 2016 teleconference.
An announcement made by Trevena following the April sit-down gave investors no hints of the differences in view.
Overall, FDA staff were clear that oliceridine offered significant benefits in pain reduction over placebo. But, compared to morphine, the picture painted in the documents is less positive.
"The oliceridine 0.5 mg dose regimen looks to be slightly less efficacious than morphine, but with similar rates of dizziness, hypoxia, nausea, and vomiting," FDA staff wrote. "The oliceridine 0.1 and 0.35 mg dose regimens appear to be even less effective than morphine, with correspondingly lower rates of selected adverse events."
What the 15 voting members of the anesthetic and analgesic drug products advisory committee make of oliceridine in Thursday's meeting will be a key test for the drug. Similarly mixed or negative reviews could spell trouble for Trevena.