Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials

Abstract

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

Post-herpetic neuralgia: currently available oral and topical medications in the management of pain – a review

“…In one study, transdermal oxycodone proved effective in a group of severe paresthesia sufferers and had fewer gastrointestinal side-effects than the oral form of the drug. Along with this, opioids in this form can sometimes be more effective in patients who are prone to non-compliance with dosage recommendations and oral medications intake [35,36].…”

“…Despite the availability of drugs from different groups that rely on diverse mechanisms of action, the treatment of neuropathic pain associated with post-herpetic neuralgia can be difficult in many patients, sometimes without satisfactory results. Nevertheless, development is still underway and research is being conducted on new pharmaceuticals that may prove effective in the treatment of PHN in the future [36].…”

“…A formulation called Olodanrigan (EMA401) seems particularly interesting. This is a highly selective antagonist of the aforementioned receptor for Angiotensin II which has shown promising results, and a good safety profile in PHN patients in two phase II trials [36,48,49]. However, one of the studies was stopped prematurely due to hepatotoxicity detected in preclinical studies with long-term use of Olodanrigan, although it was not observed in the aforementioned study itself [36,48].…”

“…Other potential future drugs worth mentioning and currently under research include the adaptor-related kinase 1 inhibitor LX9211, which is presently in Phase II clinical trials, and LAT8881 which is a fragment of human growth hormone the action of which is dependent on the peptidemodifying enzymes LANCL1 and LANCL2 [36].…”