LIBRA Study Explores mGluR5 Modulation as Novel Approach for Trigeminal Neuralgia

Details of the phase 2/3 LIBRA trial design highlight the ongoing evaluation of basimglurant, an investigational mGluR5 negative allosteric modulator, for the treatment of trigeminal neuralgia (TN), according to an abstract presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18-22 in Chicago, Illinois.¹

Presented by Amine S Tahiri, PharmD, VP Medical & Development Strategy at Noema Pharma, and colleagues, the LIBRA study (NCT05217628) is an international, multicenter, enriched randomized withdrawal trial evaluating basimglurant as monotherapy in adults with classical or idiopathic TN.¹ The study design reflects the clinical complexity of TN, incorporating both paroxysmal pain and continuous pain components while attempting to minimize prolonged placebo exposure in a population with severe, often refractory symptoms.¹

Basimglurant is a highly selective metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator designed to reduce neuronal hyperexcitability by inhibiting glutamatergic signaling pathways implicated in central pain processing.² Preclinical and translational evidence suggests mGluR5 plays a role in nociceptive transmission, providing a mechanistic rationale for targeting this pathway in neuropathic pain disorders such as TN.¹

The LIBRA trial includes a 4-week screening period followed by an 8-week open-label run-in phase, during which all participants receive once-daily oral basimglurant at doses ranging from 1.5 to 3.5 mg.¹ Patients demonstrating a clinical response, defined as at least a 30% improvement in pain-related measures including paroxysm severity, frequency, or interference, are then randomized into a 12-week double-blind withdrawal phase comparing continued basimglurant with placebo.¹ The primary endpoint for this phase is time to loss of efficacy, a design choice intended to capture durability of response rather than initial treatment effect.¹

READ MORE: CGRP Inhibitor Fremanezumab Demonstrates Efficacy in Pediatric Episodic Migraine at AAN 2026

Investigators plan to enroll approximately 200 participants, with an estimated 70 responders entering the randomized withdrawal portion of the study.¹ Secondary endpoints include changes in paroxysm severity, continuous pain, patient-reported outcomes such as the Penn Facial Pain Scale–Revised (Penn-FPS-R), Patient Global Impression of Change (PGI-C), and Migraine-Specific Quality of Life (MSQ) scores, along with safety and tolerability assessments.¹ Patients completing the randomized phase will be eligible for a 52-week open-label extension.¹

Eligibility criteria require patients aged 18 to 75 years with a confirmed diagnosis of primary TN based on ICHD-3 criteria and a baseline frequency of at least 3 daily paroxysms of moderate-to-severe intensity.³ Patients with secondary TN, significant psychiatric comorbidities unrelated to TN, or unstable medical conditions are excluded, reflecting efforts to evaluate treatment effects in a defined population.³

The development of basimglurant has been supported by regulatory interactions, including Fast Track designation from the FDA in 2022, intended to facilitate development of therapies addressing unmet needs in TN.⁴

Current TN management remains anchored in anticonvulsants such as carbamazepine, though tolerability and durability of response remain challenges for some patients. Surgical interventions are considered in refractory cases but carry procedural risks, underscoring the need for additional therapeutic approaches.⁴ Against this backdrop, the LIBRA study is designed to further characterize the efficacy and safety profile of basimglurant and its potential role in TN management.¹

Click here for more AAN 2026 coverage.

REFERENCES
1. Tahiri AS, Garibaldi G, Terril P, et al. LIBRA study: design of an enriched randomized withdrawal, placebo-controlled, phase 2/3 trial of basimglurant for trigeminal neuralgia. Presented at: 2026 American Academy of Neurology Annual Meeting; April 18–22, 2026; Chicago, IL.
2. Basimglurant (NOE-101) mechanism overview. Noema Pharma. Accessed April 18, 2026. https://www.noemapharma.com
3. Study of basimglurant in trigeminal neuralgia (NCT05217628). ClinicalTrials.gov. Accessed April 2026. https://clinicaltrials.gov/study/NCT05217628
4. FDA grants Fast Track designation to basimglurant for trigeminal neuralgia. NeurologyLive. October 24, 2022. Accessed April 18, 2026. https://www.neurologylive.com/view/fda-grants-fast-track-designation-basimglurant-trigeminal-neuralgia