IND Application Accepted for Phase 2b Trial of NOE-101 in Trigeminal Neuralgia

Author(s):

Data from the 24-week, multicenter LibraTN trial are expected to be reported in the first half of 2024.

George Garibaldi, MD

The FDA has authorized an investigational new drug (IND) application for the initiation of a phase 2b clinical trial of the mGLuR5 inhibitor NOE-101 in trigeminal neuralgia (TN), Noema Pharma recently announced. The study will evaluate the efficacy of the treatment for pain management associated with TN.¹

Dubbed LibraTN, the multicenter, 24-week, prospective, double-blind, randomized-withdrawal, placebo-controlled trial is further evaluating NOE-101, which was found to be safe and well-tolerated in previous study of adult subjects with TN. Data from the trial are anticipated to be reported in the first half of 2024. Noema Pharma announced that the first patient was dosed in LibraTN in late Feb 2022.²

“Severe neuropathic pain of the face can be excruciating and is often resistant to available treatments,” Allison S. Feldman, MPA, CEO, Facial Pain Association, said in a statement.¹ “Typically, anticonvulsants have been used to treat TN, but these drugs are not always well tolerated and need to be carefully titrated. NOE-101's promising safety profile and mechanism of action are encouraging signs that its clinical development could provide alternative treatments for those living with TN who currently have little or no options.”

New cases of TN, which is a chronic pain condition that affects the trigeminal nerve and carries sensation from the face to the brain, are thought to affect 4-5 of every 100,000 people in the US annually. Associated with nerve injury or lesion, the condition is a form of neuropathic pain. NOE-101 is a highly selective, potent, and cell-penetrant negative allosteric modulation of mGlu5 receptors, which was effective in controlling pain in animal models of neuropathic pain.

"The antinociceptive effect of NOE-101 is explained by its unique chemical and physical properties and its ability to block nuclear membrane mGlu5 receptors, the receptors overexpressed in chronic pain," said George Garibaldi, MD, chief medical officer, Noema Pharma, said in a statement.¹ “Its efficacy is similar to the gold standard achieved by morphine and the non-opiate duloxetine, but with significant potential advantages in terms of side-effects and tolerance. The LibraTN study will help us gain further understanding of the efficacy of NOE-101 in patients with TN-associated pain.”

In Oct 2021, a longitudinal, 10-year study evaluating common nondental facial pain syndromes highlighted the considerable disease burden faced by patients with these conditions, especially those with persistent idiopathic facial pain (PIFP) and neuropathic facial pain (NEUROP), who struggled to find success even when on therapies suggested by guidelines.³

Senior author Arne May, MD, PhD, professor of neurology, Department of Systems Neuroscience University of Hamburg, and colleagues aimed to prospectively characterize and compare the clinical key features and development of the 3 most common facial pain syndromes encountered in a tertiary facial pain and headache care center. A total of 411 data sets of patients with chronic facial pain were compiled, 150 of which had PIFP, 111 with TN, and 86 with NEUROP.

After each consultation and evaluation of the previous treatment, clinicians rated each patient on whether the therapy was initiated according to the German guidelines, as well as whether the patient had exploited all available means of conventional therapy. For 56.7% of the patients with PIFP, the previous therapy followed the national guideline, and only 1.3% of patients had strategies as outlined by the national guideline and were considered medically intractable. Treatment with guideline therapy was followed for 75.7% of TN cases and 66.3% of those with NEUROP.³

REFERENCES
1. Noema Pharma announces FDA investigational new drug authorization for phase 2b LibraTN study of mGluR5 inhibitor NOE-101 in trigeminal neuralgia. News release. Noema Pharma. February 14, 2022. Accessed March 8, 2022. https://www.globenewswire.com/en/news-release/2022/02/14/2384353/0/en/Noema-Pharma-Announces-FDA-Investigational-New-Drug-Authorization-for-Phase-2b-LibraTN-Study-of-mGluR5-Inhibitor-NOE-101-in-Trigeminal-Neuralgia.html
2. Noema Pharma announces first patient dosed in Phase 2b LibraTN study of mGluR5 inhibitor NOE-101 in trigeminal neuralgia. News release. Noema Pharma. February 22, 2022. Accessed March 8, 2022.https://www.globenewswire.com/news-release/2022/02/22/2389284/0/en/Noema-Pharma-announces-first-patient-dosed-in-Phase-2b-LibraTN-study-of-mGluR5-inhibitor-NOE-101-in-trigeminal-neuralgia.html
3. Ziegeler C, Brauns G, May A. Characteristics and natural disease history of persistent idiopathic facial pain, trigeminal neuralgia, and neuropathic facial pain. Headache. 2021;61(9):1441-1451. doi:10.1111/head.14212