An overview of the safety and efficacy of LX-9211 in treating neuropathic pain conditions

ABSTRACT

Introduction

LX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future.

Areas covered

This paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed.

Expert opinion

In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.

KEYWORDS:

• AAK1 inhibitors
• neuropathic pain
• LX-9211
• Lexicon Pharmaceuticals
• clathrin-dependent endocytosis

Article highlights

• Receptor mediated endocytosis plays a critical role in the regulation of many cellular membrane receptors such as the GABAA receptor.

• LX-9211 inhibits the adaptor associated kinase 1 enzyme causing a reduction in the endocytosis of the GABAA receptor.

• An elevated level of the GABAA receptor in the membrane of neurons involved in pain processing allows for their increased hyperpolarization and thus a reduction in the frequency of pain signals being generated.

• Because of this, LX-9211 is being tested for the treatment of multiple neuropathic pain conditions.

• Phase 1 studies involving LX-9211 showed it is safe as the adverse effects reported were minimal.

• Phase 2 studies with LX-9211 were conducted on patients with diabetic peripheral neuropathic pain and postherpetic neuralgia and showed the drug was effective in reducing pain in people with these disorders and was also safe.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors listed have made a direct and intellectual contribution to the work and have been approved for publication.

Additional information

Funding

This paper was not funded.