Lexicon's Non-Opioid Pain Drug Struggles in Phase 2 Trial, Raising Investor Concerns

Lexicon Pharmaceuticals faced a significant setback as its non-opioid pain medication, LX9211, failed to meet its primary endpoint in a recent phase 2 clinical trial for diabetic peripheral neuropathic (DPN) pain. The news, announced on Monday, led to a sharp 40% decline in the company's stock price, opening at 42 cents per share.

Mixed Results and Endpoint Miss

The phase 2 study, which evaluated three dosing regimens of LX9211 against placebo, showed disappointing results when data from all treatment arms were pooled. Lexicon attributed the primary endpoint miss to underperformance in the high-dose cohort. However, the company highlighted more promising outcomes from the low-dose group:

• Low-dose cohort: Mean Average Daily Pain Score (ADPS) reduction of 1.74 points
• High-dose cohort: Mean ADPS reduction of 1.38 points
• Placebo group: Mean ADPS reduction of 1.31 points

While the low-dose results appeared favorable compared to Lexicon's earlier DPN trial, the improved placebo response in this study diminished the drug's apparent efficacy. The placebo-adjusted change at the low dose decreased from approximately 0.7 points in the previous trial to 0.4 points in the current study.

Lexicon's Response and Future Plans

Despite the setback, Lexicon remains optimistic about LX9211's potential. Craig Granowitz, M.D., Ph.D., Chief Medical Officer at Lexicon, defended the results during an analyst call:

"We feel pretty confident that first of all, the trends in pain reduction will continue with the treatment arm, especially with a much lower dropout rate and with many more patients," Granowitz stated. He added, "The variance of the data should also shrink, which should improve the statistical reliability of the dataset."

The company plans to:

1. Meet with the FDA to discuss the results
2. Initiate a phase 3 program later this year
3. Increase enrollment to 300-350 subjects per arm in phase 3 studies
4. Extend the duration of future trials

Lexicon believes these adjustments will enhance the statistical power of their studies and potentially lead to more favorable outcomes.

Investor Reaction and Market Implications

The market's response to the news was decidedly negative, with investors expressing skepticism about the drug's prospects. The 40% drop in share price reflects growing concerns about LX9211's commercial viability and Lexicon's pipeline.

This development also raises questions about the broader landscape of non-opioid pain medications, an area of significant interest given the ongoing opioid crisis. The challenges faced by Lexicon highlight the difficulties in developing effective alternatives to opioids for chronic pain management.

As the pharmaceutical industry continues to search for safer pain management solutions, the outcome of Lexicon's planned phase 3 trials for LX9211 will be closely watched by investors, clinicians, and patients alike.