Nektar Therapeutics (NKTR) Study Result summary

Study objectives and design

• The Phase II-B/2b REZOLVE-AA trial evaluated rezpegaldesleukin (REZPEG) in 92 adults with severe-to-very-severe alopecia areata, using subcutaneous dosing every two weeks for 36 weeks, with a 16-week extension for responders and a 24-week off-drug follow-up.

• Patients were randomized to REZPEG 24 or 18 mcg/kg (or μg/kg) or placebo, stratified by baseline SALT score; enrollment capped very severe cases at 25%.

• Primary endpoint was mean percent reduction in SALT score at week 36; key secondary endpoints included deeper hair regrowth (SALT ≤30, ≤20, ≤10), responder analyses, and eyebrow/eyelash regrowth.

• Study included patients from Poland, Canada, and the US, median age 39, 71% women, average baseline SALT 78, and mean disease duration 2.78 years.

• Exclusion criteria included unstable disease, inadequate washout of prior treatments, and other forms of alopecia.

Efficacy results

• Both REZPEG arms more than doubled the mean percent SALT reduction at week 36 versus placebo (approx. -30% vs -6%), with statistical significance achieved after excluding four ineligible patients.

• 42% of REZPEG-treated patients achieved ≥30% SALT reduction, 36% achieved ≥50%, and 17% achieved ≥75%, all exceeding placebo.

• Dose response observed for SALT ≤30 (29% vs 8% placebo), SALT ≤20 (15.6%/14.8% vs 6.7%), and SALT ≤10 (11.5%/8.3% vs 0.7%).

• Meaningful hair regrowth, including eyebrows and eyelashes, was observed in treated patients.

• High-dose REZPEG (24 mcg/kg) demonstrated superior efficacy and is recommended for phase III.

Safety and tolerability

• REZPEG was well tolerated, with most adverse events mild or moderate and self-resolving; no new safety findings with extended dosing.

• Discontinuation due to adverse events was low (1.4%), with no discontinuations for injection site reactions.

• No increased risk of infection, MACE, thrombosis, malignancy, or JAKI-like lab abnormalities; no serious lab abnormalities requiring monitoring.

• Injection site reactions were mostly mild.

• Safety profile supports chronic use and addresses key barriers to JAK inhibitor use.