755: Libra Study (NOE-TGN-201) results: efficacy and safety of basimglurant in Trigeminal Neuralgia

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Pain Category (ICD-11), Chronic primary orofacial pain, Pharmacological treatments, Drug development

Background and Aims: Trigeminal neuralgia (TN) is a severe pain disorder without any new approved therapies since 1968. The metabotropic glutamate 5 receptors (mGluR5) play a key role in the development and expression of neuropathic pain. Following nerve injury or inflammation, mGluR5 is overexpressed in central (spinal cord, brainstem) and peripheral (trigeminal and dorsal root ganglia, primary afferent terminals) components of pain pathways, further amplifying nociceptive signaling and contributing to pain hypersensitivity.
Basimglurant, a selective, potent, and potential first-in-class mGluR5 negative allosteric modulator (NAM), targets central sensitization and peripheral pain mechanisms.

Methods: LIBRA is a multicenter, placebo-controlled, randomized withdrawal monotherapy trial of basimglurant in TN (NOE-TGN-201, NCT05217628). Patients received an 8-week open-label basimglurant monotherapy (dose escalated from 1.5 to 3.5 mg OD, Period-1); responders (≥30% improvement in pain scores) were randomized to basimglurant or placebo for up to 12 weeks (Period-2) followed by a 52-week open-label extension (OLE). During Period-2, time to loss-of-effect (LoE) of basimglurant vs placebo was assessed with two pre-specified definitions: (1) an independent committee-adjudicated method anchored on percent change from Week-8 pain scores, and (2) a conventional definition based on loss of responder status.

Results: In Period-1, 169 patients entered. At Week 8, 53% met responder criteria, with 67% mean reduction in paroxysm severity, 81% median reduction in paroxysm frequency, and similar mean reductions across additional pain dimensions.
In Period-2, 70 responders were randomized. The committee adjudicated LoE did not reliably detect clinical relapse thresholds due to low pain scores at randomization. The conventional loss of responder-status analysis showed a 54% risk reduction in time to LoE with basimglurant versus placebo (HR=0.46, p=0.040); 97% of patients entered the OLE.
Basimglurant was generally well tolerated, with dizziness, insomnia, and headache most frequently reported, and no evidence of abuse liability.

Conclusions: Basimglurant, a selective and potential first-in-class mGluR5 NAM, achieved ~70% reductions across multiple TN pain domains in the LIBRA study, with a 54% risk reduction in loss of effect versus placebo and a favorable safety profile. This is the first randomized evidence that basimglurant can provide clinically meaningful and durable relief in a refractory TN population with no new approved therapies in nearly 60 years, supporting pivotal Phase 3 evaluation.

References: -

Presenting Author: Joanna M Zakrzewska
Submitting Author: Amine S Tahiri

Senior Author: Volker Knappertz

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Henrikas Vaitkevicius: MD - Noema Pharma Inc, Boston MA, USA
• Ray Sekula: MD - Columbia University, Neurological Institute of New York, New York, United States
• Robert Lasser: MD - Noema Pharma Inc, Boston MA, USA
• Roy Freeman: MD - Beth Israel Deaconess Medical Center, Boston, MA, USA
• Joanna M Zakrzewska: MD - UCLH NHS Foundation Trust UCL, London, United Kingdom
• Volker Knappertz: MD - Noema Pharma Inc, Boston MA, USA