FDA approves Trevena’s Mu opioid for Acute pain.
Back in January 2020 the FDA had a number of expert panels voting on opioid drugs – ultimately giving negative feedback for the class. So negative in fact, it encouraged Nektar to dump their mu-opioid NKTR-181 rather than submit for approval. https://www.reuters.com/article/us-nektar-fda/us-fda-panel-votes-against-approval-of-nektars-opioid-painkiller-idUSKBN1ZD2QF
Fast forward to August and the FDA approves a mu-opioid for acute pain. Trevena’s Oliceridine (TRV130) has had a long wait for approval following a complete response letter back in 2017, but a re-submission has ended in success.
A new mu-opioid?
Typical mu-opioids like morphine, bind to the mu opioid receptor and non-selectively activate two intracellular signaling pathways: the G protein pathway to induce analgesia, while the β-arrestin pathway is thought to be responsible for the opioid-related adverse reactions. Oliceridine is a ‘biased ligand’ and activates the G protein pathway while deactivating the β-arrestin pathway.
Similar safety profile to morphine
Preclinical data demonstrate a reduced side effect profile for such biased ligands, however, the clinical side effect profile for Oliceridine is very similar to morphine with label warnings foe abuse, dependence, life threatening respiratory dependence etc (see box warning from the Oliceridine label below).https://olinvyk.com/docs/OLINVYK-FINAL-LABEL-07Aug2020.pdf
Similar efficacy to morphine
A further hope for ‘biased ligands’ is that they may demonstrate increased efficacy to standard mu-opioids, due to the fact one should not be limited by the ceiling in efficacy due to mu-related side effects. Again this doesn’t seem to be the case looking at the efficacy data in the Oliceridine label. The compound is similar or slightly less effective than morphine (see below).https://olinvyk.com/docs/OLINVYK-FINAL-LABEL-07Aug2020.pdf
The package of data re-submitted to the FDA was good enough for them to approve the drug - giving hints that opioids may still have a place in pain therapy. However, will the data convince payers to switch to this mu-opioid?
One thing is for sure: we still have a huge need for new analgesics devoid of mu-opioid side effects to have true innovative treatments for chronic pain patients.