3:05 PM
Oct 11, 2018
 |  BC Extra  |  Company News

Advisory panel narrowly rejects oliceridine for acute pain

FDA’s Anesthetic and Analgesic Drug Products Advisory Committee voted 8-7 against recommending approval of oliceridine (TRV130) from Trevena Inc. (NASDAQ:TRVN) to manage moderate to severe pain in adults for whom IV opioids are warranted.

Panelists who voted for approval thought oliceridine was at least as safe as morphine and might eventually prove to be safer, and could address unmet needs for patients allergic to or intolerant of morphine. They also thought it could be advantageous due to its fast onset and washout.

“The pharmacokinetics of this drug are attractive,” said Gregory Terman, director of the Acute Pain Service at the University of Washington Medical Center.

Oliceridine is a G protein biased μ opioid receptor (MOR; OPRM1) ligand. It is designed to preferentially stimulate MOR signaling through G protein over β-arrestin, which Trevena hypothesizes will reduce the occurrence of opioid related adverse events such as respiratory depression and gastrointestinal dysfunction.

Those who voted 'no' had lingering concerns that the safety profile was not well enough characterized, based on the size of the data set and scarcity of patients with more complex comorbidities, risk factors or concomitant medication regimens. They hoped for more data to characterize the risk that hepatic enzyme elevations and QT prolongations could lead to harm in vulnerable patient subpopulations.

“There was nothing that stood out in a majorly alarming way, except I couldn’t get over that the population in which the data were obtained were not the complex population that this will be used in," said Lonnie Zeltzer, professor of Pediatrics, Anesthesiology, Psychiatry and Biobehavioral Sciences at the University of California Los Angeles David Geffen School of Medicine.

The votes did not segregate by area of expertise. Four of the seven panelists with anesthesiology backgrounds voted in favor of approval.

Thursday's vote came after a day of curt exchanges between Trevena and FDA over the most clinically relevant and statistically appropriate methods for evaluating oliceridine’s safety and efficacy in comparison to morphine, and how they were viewed during Trevena's development program. At the meeting Trevena SVP and CMO Mark Demitrack and SVP of Scientific Affairs Jonathan Violin both asserted that FDA had not objected to the proposed Phase III primary endpoint in its end of Phase II meeting minutes. In briefing documents released ahead of the Advisory meeting, FDA said it had informed Trevena that it “did not agree” with the responder definition of the endpoint (see "FDA Reviewers Doubt Benefits of Trevena's Analgesic Over Morphine").

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

Trevena's clinical pipeline also includes migraine compound TRV250 and pain candidate TRV734. In August, Trevena said it will move TRV250 into Phase II "subject to available funds"; TRV734 has completed initial Phase I testing.

TRV250 is a small molecule G protein biased ligand targeting opioid receptor δ 1 (OPRD1; DOR). TRV734 is a G protein-biased ligand of OPRM1.

Trading in Trevena was halted on Thursday.

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