Crisugabalin Provides Significant Pain Improvements in Adults with Postherpetic Neuralgia

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A new study found Crisugabalin at 40 mg/d or 80 m/d provides statistically significant improvement in average daily pain score in adults with postherpetic neuralgia.¹

“Notably, crisugabalin was used without dose titration,” wrote investigators, led by Daying Zhang, PhD, from the department of pain medicine at The First Affiliated Hospital of Nanchang University in China. “This convenience in dosing and the efficacy of crisugabalin, 40 mg/d, allows rapid administration and dose adjustment.”

Pregabalin and gabapentin are first-line treatments for postherpetic neuralgia, but research has acknowledged the need for new treatment options. Studies have shown pregabalin is superior to gabapentin, significantly reducing pain and sleep disturbance in this patient population. However, pregabalin is linked to systemic and prominent central nervous system toxic effects including somnolence, dizziness, dry mouth, and blurred vision.

Crisugabalin, an oral calcium channel α2δ-1 subunit ligand, has demonstrated analgesic activities in animal NPN models and a better therapeutic index than pregabalin.² Additionally, the brain tissue exposure level of crisugablin was 18-fold lower than the exposure level of pregabalin, suggesting a better neurotoxicity profile.¹

Investigators sought to evaluate the efficacy of crisugablin for postherpetic neuralgia. To do so, they completed the study in 2 parts: a 12-week randomized controlled trial and a 14-week open-label extension study, conducted between November 9, 2021, and January 5, 2023, across 48 tertiary care centers across China. The primary endpoint was the change from baseline in the average daily pain score at week 12.

The phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study involved a 2-week screening period, a 7-day run-in period, and a 12-week double-blind treatment period. The trial included 366 adults who had postherpetic neuralgia with an average daily pain score of ≥ 4 on the 11-point Numeric Pain Rating Scale over the previous week, although the team excluded patients with pain not controlled by earlier therapy with pregabalin (≥ 300 mg/d) or gabapentin (≥ 1200 mg/d).

Participants were randomized 1:1:1 to receive crisugabalin 20 mg twice daily (i.e. 40 mg/d total) (n = 121), crisugabalin 40 mg twice daily (i.e. 80 mg/d) (n = 121), or placebo (n = 124) for 12 weeks. The sample had 52.7% males and a mean age of 63 years.

By week 12, participants had a least squares mean change from baseline in average daily pain score of – 2.2 for crisugabalin 40 mg/d (difference, - 1.1; 95% confidence interval [CI], - -1.6 to -0.7; P < .001) and - 2.6 for crisugabalin 80 mg/d (difference, -1.5; 95% CI, - 2.0 to -1.0; P < .001), compared with – 1.1 for placebo.

More patients on crisugabalin 40 mg/d (61.2%; 95% CI, 91.9% to 69.9%) or 80 mg/d (54.5%; 95% CI, 45.2% to 63.6%) attained ≥ 30% reduction in pain compared with placebo (35.5%; 95% CI, 27.1% to 44.6%) (P < .001). Additionally, more participants on crisugabalin 40 mg/d (37.2%; P = .002) and 80 mg/d 38%; P < .001) had a ≥ 50% reduction in pain compared with placebo (20.2%).

Furthermore, patients on crisugabalin 40 (OR, 3.58; 95% CI, 1.90 – 6.76 and OR, 3.03; 95% CI, 1.50 to 6.13) and 80 (OR, 2.93; 95% CI, 1.58 – 5.44 and OR, 3.84; 95% CI, 1.88 to 7.87) mg/d were approximately 3-fold more likely to experience ≥ 30% or ≥ 50% reduction compared with placebo.

Treatment-emergent adverse events included dizziness, hyperuricemia, weight gain, somnolence, hyperlipidemia, hypertriglyceridemia, blood creatine kinase increased, alanine aminotransferase increased, nausea, peripheral edema, urinary protein detected, lethargy, vomiting, and vertigo. The team did not observe any new safety concerns.

“Taken together, crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d,” investigators concluded.

References

1. ^{Zhang D, Lei T, Qin L, et al. Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. Published online September 25, 2024. doi:10.1001/jamadermatol.2024.3410}
2. ^{Gou X, Yu X, Bai D, et al. Pharmacology and mechanism of action of HSK16149, a selective ligand of α2δ subunit of voltage-gated calcium channel with analgesic activity in animal models of chronic pain. J Pharmacol Exp Ther. 2021;376(3):330-337. doi:10.1124/jpet.120.000315}