- Kim BS, et al. A phase 2 study of oral difelikefalin for moderate-to-severe pruritus in subjects with notalgia paresthetica (KOMFORT). D1T01.3I, EADV Congress 2022, Milan, Italy, 7–10. September.
In the phase 2 KOMFORT trial (NCT04706975), the kappa-opioid receptor agonist difelikefalin in an oral preparation was evaluated for the treatment of moderate-to-severe pruritus in patients with a confirmed diagnosis of notalgia paresthetica, a common sensory neuropathy of the back characterised by chronic pruritus. After a run-in-period, participants were treated with difelikefalin (2 mg, twice daily) or placebo for 8 weeks.
The primary study endpoint was the change from baseline in the weekly mean change of daily ≥4-point improvement (reduction) in their worst itch numerical rating scale (WI-NRS) at 8 weeks. After the double-blind study phase, there was an ongoing 4-week active extension. At the EADV meeting, Prof. Mark Lebwohl (Icahn School of Medicine at Mount Sinai, NY, USA) presented the 8-week results.
At this time, the change from baseline in WI-NRS score was −4.0 for participants treated with difelikefalin versus −2.4 for placebo (P= 0.001). “A significant difference was seen as early as day 1,” Prof. Lebwohl commented. Difelikefalin was also superior regarding a couple of secondary study endpoints: 41% of participants treated with difelikefalin achieved a ≥4-point improvement in WI-NRS score at week 8 compared with 18% in the placebo group (P= 0.007). In addition, 23% of participants treated with difelikefalin experienced a complete response at week 8 compared with 5% for placebo (P= 0.008).
The most commonly reported treatment-emergent adverse events with difelikefalin were dizziness and nausea. All adverse events were mild-to-moderate in severity. “Dizziness was common on day 1 and 2 but disappeared quickly,” Prof. Lebwohl pointed out.
The study underscores that difelikefalin has the potential to fill an urgent unmet need and warrants further clinical development in notalgia paresthetica, Prof. Lebwohl concluded.