AAK1 inhibitor shows promise as treatment for peripheral neuropathic pain

Key takeaways:

• Patients with postherpetic neuralgia were given a loading dose of 200 mg LX9211, then 20 mg maintenance or placebo for 6 weeks.
• Reduction in Average Daily Pain Score began at week 1 and continued through week 6.

BOSTON — Treatment with LX9211 reduced pain related to postherpetic neuralgia and may be a valuable addition to current options for peripheral neuropathic pain, according to a presenter at the American Academy of Neurology annual meeting.

“LX9211 is a nonopioid, oral medication designed to exert minimal effects by limiting activity of the [adapter protein-2 associated kinase 1 (AAK1)],” Anand Patel, MD, lead study investigator and chief medical officer at Conquest Research, said in his presentation.

Patel and colleagues sought to evaluate the efficacy and safety of LX9211 for pain reduction in patients with postherpetic neuralgia (PHN), given that existing treatment options do not offer adequate or sustained relief or are associated with unwanted side effects.

They conducted a phase 2, multicenter, randomized, placebo-controlled, parallel-group study and included 79 adults (mean age, 64.5 years; 59.5% women) with a history of herpes zoster rash and moderate to severe PHN pain lasting for at least 3 months after healing of the rash. Use of opioids or NSAIDS for PHN pain relief was prohibited within 2 months of screening, but participants were allowed to continue one medication prescribed specifically for PHN as long as they were at a stable doses for at least 1 month prior to screening and agreed to maintain dosing for the study duration.

After screening, participants underwent a single-blind placebo run-in period of 2 weeks before entering the double-blind, 6-week treatment period, in which they were randomized to receive a loading dose of 200 mg LX9211 followed by a maintenance dose of 20 mg (n = 38) or placebo (n = 41). A 5-week, single-blind safety follow-up period completed the study.

The primary efficacy endpoint was change in baseline to week 6 in Average Daily Pain Score (ADPS) based on the Zoster Brief Pain Inventory numerical scale, with 10 being the worst level of pain. Secondary outcomes included safety assessments and patient-recorded outcomes during and after the double-blind treatment interval.

According to results, treatment with LX9211 produced a steady reduction in ADPS compared with placebo for the entire 6-week dosing period, with distinction from placebo evident as early as week 1. While this was statistically significant throughout the dosing period, it did not reach significance at the primary endpoint. The most common treatment-emergent adverse events in the LX9211 group were dizziness, headache, nausea and constipation, but no serious drug-related adverse events were reported.

“AAK1 inhibition proves to be an exciting, novel therapeutic target,” Patel stated. “The study warrants further investigation of LX9211 as a treatment option, and that is currently in the works.”