Investigational non-opioid LTG-001 reduced acute pain in phase 2b trial

An investigational non-opioid pain medication was successful in reducing moderate-to-severe pain following abdominoplasty in a phase 2b trial, according to new data published in The New England Journal of Medicine.

Developed by Latigo Biotherapeutics, LTG-001 is a selective Nav1.8 inhibitor, a newer class of non-opioid analgesics designed to selectively block the transmission of pain. Like Journavx (suzetrigine), the first Nav1.8 inhibitor approved by the FDA in January 2025, LTG-001 is designed to target the nerve fibers that sense pain. And like Journavx, LTG-001 targets Nav1.8, which is located in nerve tissue and not the brain, and it is not associated with addiction.

“While opioids have historically been among the most effective options for treating acute pain, their associated risks underscore the importance of continued research into non-opioid approaches,” lead investigator Harold Minkowitz, M.D., co-founder of HD Research, part of the ERG Research network of clinical sites, said in a news release. “These published results of LTG-001 add to the growing body of evidence supporting the investigation of novel, non-opioid mechanisms for pain management at a time when there remains significant focus on addressing the public health impact of opioid use.”

The phase 2b trial evaluated LTG-001 compared with placebo in adults with moderate-to-severe pain following abdominoplasty, a well-established postoperative pain model. The trial enrolled 343 patients who reported moderate or severe pain after surgery. The patients were randomized to receive either a high dose of LTG-001, a low dose of LTG-001, the opioid comparator Vicodin (hydrocodone/acetaminophen), or a placebo. The high dose of LTG-001 was a 450 mg loading dose followed by 300 mg every 12 hours. The low dose was a 300 mg loading dose followed by 150 mg every 12 hours.

Researchers found that the study met the primary endpoint of the Summed Pain Intensity Difference over 48 hours (SPID48) based on scores on the Numeric Pain Rating Scale. SPID48 is a standard clinical endpoint recommended by the FDA for acute pain and post-surgery pain. It offers a measure of pain relief that accounts for changes in pain intensity over a specific interval.

Specifically, the high dose of LTG-001 achieved a statistically significant improvement in SPID48 compared with placebo. Patients receiving high-dose LTG-001 achieved a SPID48 of 62.1, which is seen as a strong indicator of pain relief. High-dose LTG-00 showed an approximately 50% greater analgesic effect than Vicodin. Time to pain relief was 52 minutes compared with 83 minutes for Vicodin.

Additionally, 52.3% of patients who received the high-dose LTG-001 remained opioid-free throughout the 48-hour treatment period, a secondary endpoint of the trial. In the placebo group, only 22.1% remained opioid-free.

Treatment-related adverse events were mostly mild to moderate, and overall adverse event levels were below those observed in the placebo arm. High-dose LTG-001 was associated with a higher incidence of fever (7% compared with 2% for placebo) and a higher incidence of lightheadedness (6% compared with 1% for placebo).

The company plans to initiate a placebo-controlled phase 3 trial in patients undergoing bunionectomy, as well as an open-label phase 3 safety trial. The FDA has already granted fast-track designation for LTG-001.

The company is also conducting a phase 2 trial of a next-generation Nav1.8 inhibitor, LTG-321, to treat patients with chronic musculoskeletal pain, starting with osteoarthritis of the knee. LTG-321 has been formulated to allow for a lower effective dose and once-daily dosing. This trial will enroll 120 patients.