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FDA rejects, removes breakthrough status from oliceridine (painkiller)

S.J.B.

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I didn't notice until now, but in November the FDA rejected oliceridine, a G protein-biased mu opioid agonist, as a treatment for moderate to severe pain.

NSFW:
TRV130.svg


From FierceBiotech:

The FDA has declined to approve Trevena's oliceridine, a mu-opioid receptor modulator for the treatment of moderate to severe pain. The complete response letter comes three weeks after an FDA advisory committee voted narrowly against the drug's approval.

Oliceridine, given the brand name Olinvo, works differently than conventional opioids, the company says. It uses a different pathway to relieve pain without causing respiratory and gastrointestinal side effects that limit other pain meds.

The FDA was not convinced, saying that Trevena had not submitted adequate safety data to support its proposed dosing. Furthermore, FDA staff outlined in briefing documents released ahead of the advisory committee meeting on Oct. 10 that it has "abuse potential, overdose potential and ability to produce physical dependence that is similar to other (opioids)." The panel came down 8-7 against oliceridine, sending the company's stock down 64%.

In the complete response letter, the FDA "requested additional clinical data on QT prolongation and indicated that the submitted safety database is not of adequate size for the proposed dosing," Trevena said in a statement. The agency also asked for additional nonclinical data and validation reports. Trevena's stock fell more than 30% Friday afternoon.

A couple weeks ago, the FDA also removed the drug's breakthrough status:

Trevena has lost its breakthrough designation for pain treatment oliceridine, just a few months after the FDA rejected its marketing application for the drug.

In an SEC filing, Trevena said that the regulator took the decision after reviewing the phase 3 results with the mu opioid receptor-targeting drug and concluding that "under the conditions studied, these data were not sufficient to support the continuation of FDA's previously granted breakthrough therapy designation."

Last November, Trevena was hit hard by the FDA's decision not to approve oliceridine for moderate to severe pain, despite the company's arguments that the drug reduces the risk of respiratory and gastrointestinal side effects seen with other painkillers--the profile that underpinned the FDA's BTD.

As it turned out, the agency said Trevena had not submitted adequate safety data to support its proposed dosing, and it said the drug had abuse and overdose potential similar to other opioid drugs. It also asked for additional clinical data on QT prolongation, a marker that can indicate underlying cardiovascular risk.

On the plus side for Trevena, it now seems the FDA has agreed that its safety database will support a refile for oliceridine, at a maximum daily dose of 27mg, providing it completes a phase 1 study in healthy volunteers that gives the all-clear on the QT interval question.

All that said, oliceridine still has a chance of being approved.

There is a lot of work going on right now looking at alternatives to traditional mu opioid painkillers, with G protein-biased mu agonists, mu/kappa and mu/delta agonists, and nociceptin/orphanin FQ/mu agonists being the categories which seem to be attracting the most attention. It will be interesting to see which of these, if any, will lead to the first approved drug.
 
Interesting!
I had no idea! I actually started a thread here, probably more than a year ago now, about trevena when i first stumbled on it.
Thanks for posting!
 
What an interesting structure. I read the FDA briefing which concluded that it was rewarding and had no clinical advantages. Still, it's a really great structure to add to any training set; so many unusual (but not unknown) features. My problem is just limiting how many I test... a server chugging away for 3 weeks is fine right until the moment you realize you included something you didn't mean to or got a structure wrong which moves everything out.
 
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