Nalbuphine: aspiring to become another treatment for prurigo nodularis?

After demonstrating positive results for all endpoints in the PRISM trial, nalbuphine could be a candidate for an approved treatment for prurigo nodularis. The agent performed significantly better than placebo in reducing itch ≥4 points on the worst itch numeric rating scale (WI-NRS), while also improving quality-of-life and skin lesions.

The latest results of the phase 2b/3 PRISM trial (NCT03497975) were eagerly awaited, as currently approved pharmacologic therapies for prurigo nodularis are still lacking. The trial investigated nalbuphine, a dual κ-opioid receptor agonist/µ-opioid receptor antagonist as treatment for pruritus in prurigo nodularis [1]. Of note, abuse and addiction potential in activation of the κ-opioid receptor was found to be very low to non-existent. Included were 353 patients, randomised to receive either placebo or 162 mg of oral nalbuphine in an extended-release formulation, twice daily, after a 2-week titration.

The participants comprised a multi-ethnic group with a mean age between 56–60 years and a slight predominance for women. In both arms, baseline mean WI-NRS values of 8.6 and 8.7 stood for very severe itch. As for quality-of-life, the participants presented with mean scores of >80 out of 100 points in the Itchy-quality-of-life (ItchyQoL) score. “The majority of the population (60%) had 20–100 nodules which is a lot, 30% had over 100 nodules, and only 10% had up to 20 nodules,” Prof. Sonja Ständer (University Medical Centre of Münster, Germany) said.

PRISM met its primary endpoint with significantly more participants responding to nalbuphine with a ≥4-point reduction in their WI-NRS compared with placebo at week 14 (24.7% vs 13.9%; P=0.0157). The significant difference between the 2 responder curves of nalbuphine and placebo began at week 6 (P=0.0027) and continued thereafter. Similarly, the quality-of-life improved significantly from week 6 onwards. The study also looked at the amelioration of pruriginous lesions. “Here we can say that nalbuphine interrupts the itch-scratch cycle and that the lesions can heal,” Prof Ständer stated.

Safety results were consistent with nalbuphine’s known profile. In line with the nalbuphine versus placebo results, the incidence of ≥1 treatment-emergent adverse event differed between the initial 2-week titration period (66.1% vs 31.3%) and the following fixed-dose therapy (48.2% vs 44.9%). Most common were gastrointestinal disorders, dizziness, and headache. “The safety profile is of course the issue with this drug, but on the other hand we can easily manage them and it’s all in the mild and moderate range,” Prof. Ständer commented.

All in all, she was very optimistic about nalbuphine as a potential novel treatment in prurigo nodularis.

1. Ständer S. Oral nalbuphine extended-release is effective in severe prurigo nodularis–associated pruritus: results from a phase 2b/3, double-blind, placebo-controlled study. 3K, EADV Congress 2022, Milan, Italy, 7–10 September.

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Posted on 5 November 2022