Latigo’s Non-Opioid Painkiller Matches an Opioid Combo in Phase 2b Trial

An experimental non-opioid painkiller eased pain after surgery about as well as a common opioid combination — while cutting the need for opioid rescue medication — in a mid-stage trial published in the New England Journal of Medicine on July 30, 2026.

The drug, LTG-001, is an oral selective inhibitor of Nav1.8, a sodium channel carrying pain signals along nerves. Developer Latigo Biotherapeutics of Thousand Oaks, California designed it to deliver opioid-level relief without acting on the brain the way opioids do.

How the trial was designed

The Phase 2b study randomised 343 patients with moderate-to-severe pain after abdominoplasty into four equal groups: low-dose LTG-001, high-dose LTG-001, hydrocodone/acetaminophen, or placebo, over 48 hours.

The surgical model is a deliberate choice used widely in analgesic development. Abdominoplasty produces reliable, substantial, predictable pain in otherwise healthy patients, at a known time, with a known duration.

That combination makes it possible to detect a treatment effect cleanly. Chronic pain studies contend with variable baselines, fluctuating symptoms and large placebo responses; a defined surgical injury largely removes those problems — which is why a drug proven here still has to prove itself in other pain settings separately.

What SPID48 measures

The main measure was SPID48, a summed score of pain-intensity reduction over 48 hours.

Patients rate pain at intervals; the difference from baseline is calculated at each point and the values summed across the period. The result captures cumulative relief rather than a snapshot.

The design matters because a drug providing strong but brief relief scores differently from one providing moderate sustained relief, and for post-surgical pain the sustained version is generally what patients need.

What it found

The high dose scored highest (least-squares mean 185.3), ahead of hydrocodone/acetaminophen (164.1), the low dose (161.1) and placebo (123.2), reaching high statistical significance versus placebo.

The high dose also reduced opioid rescue use by 7.35 morphine milligram equivalents (p=0.01) and left 30 percentage points more patients avoiding opioid rescue altogether (p<0.001). Median time to meaningful relief was 51.7 minutes on the high dose versus 87.5 on placebo.

Why the rescue-medication result carries most weight

Of the outcomes reported, the proportion of patients avoiding opioids entirely is the most clinically meaningful.

Pain scores are continuous and their interpretation is contested — how much difference on a summed scale constitutes a benefit a patient would notice is genuinely debatable.

Whether a patient took an opioid is binary and directly relevant to the problem the drug exists to solve. Thirty percentage points more patients never needing one is a large effect on the outcome that matters, and it is harder to argue with than a score difference.

How to read the comparison

The trial was not designed to prove superiority over the opioid, and the high dose scoring above it is a favourable result rather than a demonstrated advantage — establishing that would require a trial powered for that comparison.

The comparator itself is also worth noting. Hydrocodone/acetaminophen is a moderate-strength combination widely used after surgery, not a potent opioid, so matching it does not imply matching what is used for severe pain.

The low dose performing roughly at the opioid level and below the high dose does establish a dose-response relationship, which is meaningful evidence that the effect is real rather than chance.

What is next

With opioid dependence a persistent risk of post-surgical pain control, drugs blocking pain at the nerve rather than in the brain have drawn intense interest.

Latigo plans a Phase 3 trial in bunionectomy and a safety study in the second half of 2026, with topline results expected in the second half of 2027.

Why post-surgical prescribing became the target

The emphasis on avoiding opioid rescue reflects how surgical pain management came to be seen as an entry point into dependence.

Research following patients prescribed opioids after routine surgery found that a small but consistent proportion were still using them months later, having had no prior opioid exposure. The absolute percentage is low; applied to the enormous number of operations performed annually, the resulting number of people is not.

Prescription size mattered measurably. Larger initial prescriptions and longer durations predicted persistent use, and leftover tablets in homes became a source of non-medical use by others.

The response has been substantial: prescribing guidelines, smaller default quantities, multimodal regimens combining non-opioid analgesics, and monitoring programmes. Prescribing has fallen considerably.

That progress created its own problem, which is undertreated pain in patients who genuinely need strong analgesia and encounter clinicians reluctant to provide it. A drug offering comparable relief without dependence risk would resolve a bind that current tools only trade off — which is why an endpoint counting patients who never needed an opioid is the one the field is watching.

Bunionectomy is the other standard analgesic model, chosen for the same reasons as abdominoplasty. Using a different procedure in Phase 3 tests whether the effect generalises beyond one type of surgical injury. Clinical research news, not medical advice.