Mu-Receptor Agonists

There are three types of opioid receptors (mu, kappa, delta).  Activation of the opioid receptors stimulate G proteins which initiate the intracellular communication process leading to the physiologic responses. 
 
All three opioid receptors cause analgesia and respiratory depression. Kappa and Mu receptors also cause sedation. Mu receptors can be divided into two types, Mu1 and Mu2. Stimulation of Mu1 receptors cause analgesia, bradycardia and respiratory depression, while Mu2 receptors cause respiratory depression, physical dependence and euphoria. 
 
Morphine and synthetic opioids are mu-opioid receptor agonists. Three selective Mu-opioid receptor agonists are in the late stages of development with two having PDUFA dates through May 2019. None of the three have FDA Priority Designations.
 
Oliceridine (Olinvo fromTrevena) PDUFA: November 2, 2018
 
Oliceridine is being developed by Trevena. An FDA review of oliceridine felt that data did not support the drug having less respiratory depression than morphine and the highest dose (0.5mg) appeared to be less efficacious than morphine in analgesic effects, but similar in ADR.  The report also noted that lower doses of oliceridine had fewer ADR, but less analgesic effects. All strengths of olicerdine provided more analgesic effect than placebo. An early study provided evidence that dosing is not affected by renal impairment.  Oliceridine will most likely be a schedule II drug. An FDA advisory committee voted 8-7 to not recommend approval of oliceridine and recommended additional clinical trials. The committee also noted the potential for QT prolongation.
 
Trevena announced that top line results from two Phase III oliceridine trials found the drug to be superior to placebo in patients with moderate-to-severe acute pain.  The 0.35 mg and 0.5 mg doses of oliceridine demonstrated efficacy comparable to morphine within 24-48 hours. Following a 1.5 mg loading dose, all oliceridine dose regimens (0.1 mg, 0.35 mg, and 0.5 mg) were able to display rapid onset with statistically significant efficacy by 5 to 15 minutes.
 
Our knowledgebase contains no published studies about oliceridine. 
 
Sufentanil Sublingual (Dsuvia from AcelRx Pharmaceuticals) PDUFA: November 3, 2018
 
Dsuvia, being studied for being studied for post-op and battlefield pain, is a sublingual tablet administered by a pen like applicator. In a review the FDA found sublingual sufentanil tablets to be efficacious for moderate-to-severe acute pain but had concerns over the maximum dosing and the risk of misplaced tablets due to their small size. AcelRx and the FDA have both proposed a REMS program for sublingual sufentanil tablets. The FDA’s Anesthetic and Analgesic Drug Products Advisory Committee voted 10-3 to recommend approval of sublingual sufentanil tablets.
 
In a 76 patient, Phase III trial, patients treated with sublingual sufentanil experienced a mean decrease in pain intensity of 35% at 1 hour.  In a 143 patient, phase III trial, sublingual sufentil demonstrated efficacy compared to placebo in control of outpatient abdominal surgery pain.
 
Our knowledgebase contains seven published studies for sublingual sufentanil.  Click on this link for one-month’s access to the Pharmaceutical Pipeline Tracker @ $115 with no long-term commitment: https://www.prescriberight.com/subscription-offers.html  then sign into www.prescriberight.com with your user name and password to conduct a single drug search for sufentanil to view the studies.
 
NKTR-181 (Nektar)PDUFA: May 28, 2019 
 
NKTR-181 being studied for moderate to severe chronic low back pain has reduced permeability across the blood-brain barrier, so it may less euphoria and sedation. Nektar announced that NKTR-181 reduced pain compared to placebo in 600 opioid-naive patients with moderate to severe chronic low back pain.  A small trial suggested that NKTR-181 had a lower abuse potential than oxycodone. 
 
There is one published study in our knowledgebase which concluded that NKTR-181 demonstrated delayed onset of CNS effects and significantly lower abuse potential scores compared with oxycodone in recreational opioid users.