Latigo’s selective NaV1.8 inhibitor LTG-001 demonstrated significant pain relief, rapid analgesia and opioid-sparing potential in Phase 2b postoperative pain results published in NEJM.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Latigo Biotherapeutics has reported that The New England Journal of Medicine (NEJM) has published positive Phase 2b results for its investigational selective NaV1.8 inhibitor LTG-001, demonstrating clinically meaningful pain relief in adults with moderate-to-severe acute postoperative pain following abdominoplasty.
According to the company, the publication represents only the second original research article in The New England Journal of Medicine reporting clinical results for a novel acute pain therapy in the past 15 years, highlighting the growing interest in non-opioid approaches to pain management.
LTG-001 Designed as a Selective Non-Opioid NaV1.8 Inhibitor
LTG-001 is an investigational oral, selective NaV1.8 inhibitor belonging to a new class of non-opioid analgesics designed to selectively block pain signal transmission in peripheral sensory neurons. By targeting the source of pain without directly acting on opioid receptors, the therapy is being developed as a potential alternative to opioid-based pain management for patients with acute pain.
Phase 2b Trial Evaluated LTG-001 Following Abdominoplasty
The published Phase 2b trial (NCT07102459) was a randomized, double-blind, placebo- and active comparator-controlled study that enrolled 343 adults experiencing moderate-to-severe pain following abdominoplasty. Participants were randomized in a 1:1:1:1 ratio to receive high-dose LTG-001 (450 mg loading dose followed by 300 mg every 12 hours), low-dose LTG-001 (300 mg loading dose followed by 150 mg every 12 hours), hydrocodone bitartrate 5 mg/acetaminophen 325 mg (Vicodin) administered every six hours as the active comparator, or placebo. The study evaluated efficacy using the Summed Pain Intensity Difference over 48 hours (SPID48), a well-established endpoint for assessing postoperative analgesic benefit.
The study met its primary endpoint, with high-dose LTG-001 demonstrating statistically significant improvement in SPID48 compared with placebo. The investigational therapy provided rapid, clinically meaningful pain relief while also demonstrating opioid-sparing potential, supporting its continued clinical development for acute postoperative pain.
High-Dose LTG-001 Demonstrated Rapid Analgesia and Opioid-Sparing Potential
Beyond achieving the primary endpoint, several secondary findings further supported the clinical activity of LTG-001. High-dose LTG-001 achieved a SPID48 value of 62.1, which the company described as the highest analgesic effect reported in a published industry-sponsored abdominoplasty trial. Compared with hydrocodone/acetaminophen, the high-dose regimen demonstrated approximately 50% greater analgesic effect and achieved a median time to meaningful pain relief of approximately 52 minutes, compared with 83 minutes for the opioid comparator. In addition, 52.3% of participants receiving high-dose LTG-001 remained opioid-free throughout the 48-hour treatment period, compared with 22.1% of participants in the placebo group.
The lower-dose LTG-001 regimen also demonstrated statistically significant improvement over placebo, achieving a SPID48 value of 37.8 and demonstrating a clear dose-response relationship. According to the publication, its analgesic effect was broadly comparable to that observed with the hydrocodone/acetaminophen comparator.
Safety Profile Supported Continued Clinical Development
The favorable efficacy results were accompanied by a favorable safety profile. Treatment-emergent adverse events were predominantly mild to moderate, and overall adverse-event rates were reported to be lower than those observed in the placebo group. No additional safety findings beyond those described in the publication were reported.
Investigators Highlight Growing Need for Non-Opioid Pain Therapies
Neil Singla, M.D., Chief Medical Officer of Latigo, stated that publication NEJM represents an important milestone for LTG-001 and adds to the growing scientific evidence supporting non-opioid approaches to pain management. Lead investigator Harold Minkowitz, M.D., noted that while opioids remain effective treatments for acute pain, the published findings reinforce ongoing efforts to develop effective non-opioid alternatives that may help reduce opioid exposure in postoperative care.
NEJM Publication Strengthens Clinical Evidence for LTG-001
Publication of the Phase 2b findings provides peer-reviewed validation of LTG-001’s clinical activity and represents an important milestone in the development of selective NaV1.8 inhibitors as potential non-opioid therapies for moderate-to-severe acute postoperative pain. The results add to the growing body of clinical evidence supporting novel analgesic strategies aimed at providing effective pain relief while reducing reliance on opioid medications.
Reference
Phase 2b Trial of a NaV1.8 Inhibitor for Acute Pain | New England Journal of Medicine
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.