Novel biologic agent shows promise in severe AA

Rezpegaldesleukin led to reductions in Severity of Alopecia Tool (SALT) scores in the modified intention-to-treat (mITT) cohort. At the higher dose, SALT scores in patients with alopecia areata (AA) decreased by approximately 30% at week 36.

A first-in-class biologic agent targeting regulatory T cells was investigated in the Rezolve AA (NCT06340360), a phase 2b study in patients with severe-to-very severe AA [1]. Rezpegaldesleukin (“rezpeg”), as referred to by the presenter, Prof. David Rosmarin (Indiana University School of Medicine, IN, USA), stimulates regulatory T-cell activity via the interleukin-2 (IL-2) receptor without activating conventional T cells [1,2]. The drug is also under investigation for other dermatologic indications, including atopic dermatitis [1].

The study enrolled 92 adult patients, randomised in a 3:3:2 ratio to receive rezpeg at 24 µg/kg every 2 weeks (Q2W), 18 µg/kg Q2W, or placebo [1]. The primary endpoint was the mean percentage reduction in SALT score at week 36. The study included a 24-week post-treatment follow-up and a 16-week blinded extension for patients with a partial response.

Baseline characteristics included a mean age of approximately 40 years, with 62.9%–78.4% female participants, and mean baseline SALT scores of 80.7 (24 µg/kg) and 76.3 (18 µg/kg). The median time since AA onset ranged from 6.1 to 7.0 years.

In the primary analysis, reductions in SALT score were -28.2% (24 µg/kg), -30.3% (18 µg/kg), and -11.2% (placebo), with neither comparison reaching statistical significance (P=0.186 and P=0.121). However, 4 patients with major protocol deviations (e.g. inadequate washout or unstable disease) were identified and excluded in a post hoc mIIT analysis. In this analysis, results were more favourable: -29.6% (24 µg/kg; P=0.049), and -30.4% (18 µg/kg; P=0.042) versus -5.7% for placebo.

Among secondary endpoints in the mITT population, 29.0% and 21.9% of patients achieved SALT ≤30, and 15.6% and 14.8% achieved SALT ≤20, compared with 8.4% and 6.7% in the placebo arm. Prof. Rosmarin further reported that during the blinded extension phase, additional patients reached these thresholds, with increases of 3 patients for SALT ≤20 and 7 for SALT ≤30. Full extension data up to 1 year are expected soon.

SALT ≤10 responses (mITT) were observed in 11.5% (higher dose) and 8.3% (lower dose) of patients, compared with 0.7% in the placebo group. The mITT analysis demonstrated improvements in eyebrow and eyelash regrowth, with placebo-adjusted rates of 15% and 7%, and 18% and 15%, respectively.

In terms of safety, injection-site reactions, mostly mild-moderate, were the most common treatment-emergent adverse events, occurring in 91.7% of rezpeg-treated patients versus 30% in the placebo group.

According to Prof. Rosmarin, cumulative exposure to rezpeg across 11 studies (approximately 381 patient-years) has not been associated with increased risks of major cardiovascular events, thrombosis, infections, malignancies, acne, or Janus kinase (JAK) inhibitor-associated adverse events requiring laboratory monitoring.

Phase 3 development of Rezpegaldesleukin in AA is planned using a higher dose of 24 µg/kg Q2W.

Rosmarin D, et al. Novel regulatory T-cell enhancing biologic rezpegaldesleukin: phase 2b efficacy and safety results following 36-weeks of therapy in severe-to-very-severe alopecia areata. S023 Late-Breaking Research: Session 1. AAD 2026, 27–31 March, Denver, CO,USA.
Dixit N, et al. J Transl Autoimmun. 2021:4:100103.