⚡New agent for dialysis-associated pruritus

Good morning — it’s Saturday, August 30, and we’re covering a new kappa agonist for hemodialysis-associated pruritus, the second pivotal trial of upadacitinib in alopecia areata, and more.

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A Phase 3 trial published in The BMJ found that anrikefon significantly reduced itch intensity in hemodialysis patients with pruritus.

Anrikefon is a novel, peripherally restricted kappa opioid receptor agonist that targets the imbalance between kappa and mu opioid receptor signaling implicated in chronic kidney disease-associated pruritus.

Investigators randomized 545 hemodialysis patients with moderate-to-severe pruritus to intravenous anrikefon (0.3 μg/kg) or placebo three times weekly for 12 weeks, followed by a 40-week open-label extension.

At baseline, patients reported severe pruritus, with a mean score of 7/10 on the Worst Itch Numeric Rating Scale (WI-NRS; range 0–10).

By Week 12, 37% of patients receiving anrikefon achieved a clinically meaningful ≥4-point reduction in WI-NRS versus 15% on placebo. Quality of life also improved more with anrikefon on the 5-D itch scale (−5 vs −3 with placebo; range 5–25). Both outcomes were significant (P < 0.001). In the open-label phase, quality-of-life scores continued to improve, supporting durability of benefit.

The drug was generally well tolerated, although dizziness occurred more frequently with anrikefon.

Limitations included the absence of an active comparator and no evaluation of physical dependence. However, a preclinical study suggests low misuse potential, and a prior Phase 2 study found no withdrawal symptoms following discontinuation.

Anrikefon’s trial design mirrored that of difelikefalin, the first kappa agonist approved in the US and Europe for pruritus in patients on hemodialysis. Difelikefalin achieved similar efficacy but was associated with higher rates of diarrhea. Still, cross-trial comparisons should be interpreted with caution. 

> Upadacitinib advances in severe alopecia areata as second pivotal trial confirms efficacy: AbbVie announced positive topline results from Study 1 of the pivotal Phase 3 UP-AA program, supporting the efficacy of upadacitinib (Rinvoq) in severe alopecia areata. The findings closely mirrored results of the companion trial (Study 2) reported last month. Study 1 randomized adults and adolescents with severe alopecia areata to upadacitinib 15 mg or 30 mg, or placebo for 24 weeks. Baseline scalp coverage was low, averaging 16% (mean Severity of Alopecia Tool [SALT] score 84; range 0–100). By Week 24, 45% and 55% of patients on upadacitinib 15 mg and 30 mg achieved ≥80% scalp coverage (SALT ≤20), compared with just 2% on placebo (P < 0.001). Key secondary endpoints were also met, including SALT ≤10 responses and improvements in eyebrow and eyelash regrowth. Safety findings were consistent with prior studies. Serious adverse events occurred in 2% of upadacitinib-treated patients versus 1% of placebo patients. One case of breast cancer was reported in the 15 mg arm, though causality remains uncertain. An approval in alopecia areata would add to Rinvoq’s growing immunology footprint. The JAK inhibitor generated $2.03 billion in global sales in Q2 2025, a 42% year-over-year increase.

> Ameluz-PDT clears superficial basal cell carcinoma with favorable safety and cosmetic outcomes: A Phase 3 trial published in JAAD found that red light photodynamic therapy (PDT) with 10% aminolevulinic acid gel (Ameluz) achieved significantly higher clearance of superficial basal cell carcinoma (sBCC) than placebo-PDT, while maintaining favorable safety and cosmetic outcomes. Investigators randomized 187 patients with sBCC to 1–2 cycles of Ameluz-PDT or vehicle-PDT. All main target lesions were excised 12 weeks post-treatment to confirm histological clearance. Clinical clearance was 83% with Ameluz-PDT vs 21% with vehicle-PDT, and histological clearance was 76% vs 19% (both P < 0.0001). In the Ameluz-PDT group, clearance rates declined with size, ranging from 91% for small tumors (≤81 mm²) to 73% for larger ones (≥165 mm²). Notably, even non-cleared lesions shrank by a median of 42%, and nearly 90% of patients rated cosmetic outcomes as good or very good. Treatment was well tolerated, with no discontinuations or severe complications. Pain scores averaged 4.5/10 with Ameluz-PDT and declined in the second cycle. Limitations included the small number of face/scalp lesions (2%) and short follow-up, though 60-month monitoring is ongoing. The authors highlight Ameluz-PDT as a potential alternative to excision in selected patients, with shrinkage of tumors in non-cleared cases indicating a possible neoadjuvant role. Biofrontera, the study sponsor, plans FDA submission of Ameluz for sBCC.

> Low- vs high-fluence picosecond alexandrite laser for Nevus of Ota: A randomized split-lesion trial published in JAAD found that low-fluence picosecond alexandrite laser (LF-PSAL) was non-inferior to high-fluence PSAL (HF-PSAL) for treating Nevus of Ota in children under 5 years, while producing fewer adverse effects. Sixty-four patients underwent three sessions with each lesion split to receive HF-PSAL (immediate whitening endpoint) or LF-PSAL (erythema endpoint). Clearance was graded on a 5-point scale, from 1 (<25%) to 5 (≥95%). Among children under 5, mean clearance scores were similar for LF- and HF-PSAL (4.5 vs 4.6; P = 0.68), but in older patients HF-PSAL was superior (4.5 vs 4.0; P < 0.05). Adverse events were markedly lower with LF-PSAL, including scabbing (7% vs 100%), blistering (0% vs 37%), and post-inflammatory hypopigmentation (0% vs 35%). Two women developed persistent melasma on HF-treated sides. Mean pain scores were lower with LF-PSAL (3.2 vs 4.9; range 0–10; P < 0.001). The authors suggest the age-related difference in clearance reflects thinner skin and a more superficial distribution of lesions in younger children. They concluded that LF-PSAL may offer a safer treatment option, particularly for young children and patients at risk of melasma.

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