Lexicon's AAK1 Inhibitor Disappoints in Phase II Postherpetic Neuralgia Study

Courtesy of Getty Images

Lexicon Pharmaceuticals’ LX9211 fell short of its primary efficacy endpoint, according to topline data from the Phase II RELIEF-PHN-1 study in post-herpetic neuralgia, the Texas biopharma announced Wednesday.

After six weeks of follow-up, patients treated with Lexicon’s candidate saw a drop of 2.42 points in the average daily pain score compared to baseline values. In placebo comparators, scores decreased by 1.62 points. The placebo-adjusted effect of .80 was not statistically significant, with a p-value of .12.

In reaction to the news, the company’s stocks dipped 11% in after-hours trading.

However, despite missing its efficacy metric, Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer, said that RELIEF-PHN-1 provided “clear evidence of effect supporting the further development of LX9211.”

The company is preparing to submit these results to an upcoming medical conference and for publication in a peer-reviewed journal.

In particular, the company pointed to a notable separation of effect from the placebo, evident starting one week after treatment initiation. The average placebo-adjusted treatment effect over six weeks was .80 and was statistically significant in favor of LX9211.

Post-herpetic neuralgia is the most common complication of shingles caused by the herpes zoster virus. Its symptoms affect primarily the skin and nerve fibers and include persistent pain, hypersensitivity, itching and numbness.

RELIEF-PHN-1 is a randomized, double-blinded, parallel-group and proof-of-concept study enrolling nearly 80 post-herpetic neuralgia patients to assess the efficacy and pharmacokinetics of LX9211, as compared with placebo.

The candidate under investigation is an oral selective inhibitor of adaptor-associated kinase 1. LX9211 and its AAK1 target were identified under a neuroscience drug discovery partnership with pharma powerhouse Bristol Myers Squibb.

Aside from efficacy, RELIEF-PHN-1 also looked at LX9211’s safety and found that adverse events were broadly consistent with previously reported data. Lexicon reported no serious toxicities or deaths from the study. The most common side effect was dizziness.

Promising Player in Neuropathic Pain

Last month, Lexicon unveiled more positive data from LX9211 in diabetic peripheral neuropathic pain. Findings from the RELIEF-DPN-1 trial, presented at the 16th Annual Pain Therapeutics Summit, showed that the candidate met its primary endpoint of significantly reducing average daily pain score compared to the placebo.

LX9211 also induced significant improvements in burning pain and the interference of pain in sleep.

Moreover, while the candidate’s effects slightly tapered off in the 5-week run-off period, Lexicon reported no evidence of rebound pain or withdrawal. As in RELIEF-PHN-1, treatment with the investigational compound did not trigger serious adverse events or deaths.

The FDA has given Lexicon’s candidate the Fast Track designation for development in diabetic peripheral neuropathic pain.