TRV734 from Trevena is an investigational substance which recently underwent its first clinical trial in humans. Trevena specializes in G-protein-biased ligands, and this particular orally bioavailable ligand acts on the mu-opioid receptor.

In prior nonclinical studies, it was found that it had the potential to offer analgesic effects. The clinical trials back up this prospect and suggest that it could have some strong benefits in terms of pain management since not only does it work as an analgesic, it also appears to have fewer gastrointestinal side-effects.

How Does TRV734 Differ From Alternatives

This oral chemical acts on the mu-opioid receptor, but unlike morphine and oxycodone, it has weak B-arrestin recruitment. B-arrestin inhibits the pain relief of opioids and is responsible for many of the side effects too. It is the comparatively limited B-arrestin action which makes TRV734 so promising.

TRV734 is Well Tolerated

Initial studies suggest that TRV374 offers analgesic effects without side-effects such as constipation or respiratory depression. It is believed to be safer than oxycodone while offering a similar level of pain relief.

One of the challenges of using opioids for pain relief is that while they do have strong analgesic properties they are not good for long-term use. They can cause gastrointestinal distress, dependency, analgesia intolerance and respiratory depression. The risk of addiction is high and there is a strong risk of overdose as well.

There have been many attempts made by pharmaceutical companies and medical experts to mitigate these side effects. Laxatives such as methylnaltrexone offer some benefits and there are drugs such as the opioid and SNRI tapentadol which can also help to reduce the side effects of traditional opioids, however, these options tend to be expensive and come with side effects of their own.

TRV374 is Bioavailable and Can Be Taken With Food

In one two-part trial, TRV734 was given to a study group of healthy humans. The group was split up evenly with some participants having had a high-fat meal, some a standard meal and others three split portions following a fast. The study participants showed signs of pupil constriction, which matches opioid activity. They also showed signs of improved ability to tolerate cold-induced pain for four to six hours after the dose.

Other participant groups were given a placebo or 10mg immediate-release oxycodone. The TRV734 groups reported no serious or severe adverse reactions. Some users did report nausea, vomiting, dizziness or tiredness, however, these side-effects were reported in the oxycodone group too. Bowel function results were better for those using TRV374 than for those using oxycodone, as a group.

What Does This Mean for the Future?

At the moment, TRV734 is still under investigation and the FDA has not approved it for use by patients in the United States. The recent trials are the first steps towards getting the drug approved. The FDA does not approve drugs until there is significant and sustained evidence showing that they can be safely used.

The initial trials are promising. Opioid safety is a huge problem. Those who are suffering from severe acute pain must be careful when taking opioids. The use of opioids for chronic pain and in palliative care must be carefully monitored and controlled. Trevena believes that TRV734 is a massive breakthrough in terms of safety and tolerability while offering similar performance for pain relief. This bioavailable G-protein-biased ligand could revolutionize the way that moderate to severe pain is treated. More research is required before TRV734 can be used in the mainstream, however, in the next few years, it could become a viable and affordable alternative to using laxatives and SNRIs.