Nektar Therapeutics Shares 52-Week REZOLVE-AA Data as Rezpeg Boosts SALT ≤20 Responses in Alopecia Areata

Key Points

• Extended dosing to 52 weeks increased the proportion achieving SALT ≤20 from 15.6% at week 36 to 27.6% at week 52, with the high‑dose versus placebo comparison reaching statistical significance (p=0.049).
• In the 16‑week blinded extension of prior non‑responders, 8 new SALT ≤20 responders were seen among 27 patients on rezpeg (29% at 18 mcg/kg, 31% at 24 mcg/kg), and patients achieving ≥75% SALT reduction rose from 4% at week 36 to 26% at week 52.
• The 52‑week dataset showed no new safety signals and no extension discontinuations, with mostly mild‑to‑moderate AEs and a median injection‑site reaction resolution of five days; Nektar is planning an FDA end‑of‑Phase‑2 meeting in Q2 to align on Phase 3 strategy.

Nektar Therapeutics NASDAQ: NKTR presented 52-week top-line results from a 16-week blinded treatment extension of its Phase 2b REZOLVE-AA study evaluating rezpegaldesleukin (rezpeg) in adults with severe to very severe alopecia areata, emphasizing that additional dosing beyond 36 weeks increased the proportion of patients reaching the FDA registrational endpoint of SALT score ≤20.

Company focus on Treg mechanism and multiple indications

President and CEO Howard Robin said the company’s strategy is to advance a “first-in-class regulatory T cell, or Treg mechanism,” targeting autoimmune and inflammatory diseases. Rezpeg is “a first-in-class IL-2 pathway biologic designed to selectively expand regulatory T cells,” Robin said, adding that Nektar’s Phase 2 program spans atopic dermatitis, alopecia areata, and type 1 diabetes.

Robin said Nektar plans to initiate the Phase 3 ZENITH-AD atopic dermatitis studies “around the middle of this year,” and, if successful, expects first pivotal data in “mid-2028” and a first BLA submission “by the end of 2029.” He also noted rezpeg is being studied in new-onset stage 3 type 1 diabetes through a TrialNet-sponsored and funded Phase 2 study, with initial data expected in 2027.

Why Nektar sees an opening in alopecia areata

Chief Research and Development Officer Jonathan Zalevsky said alopecia areata affects “roughly 160 million people worldwide,” with about “30 million new cases diagnosed every year.” He described the current systemic treatment landscape as dominated by oral daily JAK inhibitors, which he said carry “multiple box warnings” and “high relapse rates after patients stop treatment.”

Zalevsky argued that a less frequent dosing option and a therapy with “an extended biologic pharmacodynamic effect” could improve durability and persistence, and suggested rezpeg’s Treg expansion mechanism may help restore immune tolerance at the hair follicle. He also cited an anonymous survey of 131 board-certified dermatologists indicating many would consider alternatives before initiating a JAK inhibitor, as well as an external analysis of Symphony claims data showing poor persistence on low-dose baricitinib, with a median time on therapy of approximately 3.7 months among patients who stayed on 2 mg treatment.

REZOLVE-AA design and what the extension tested

Chief Medical Officer Mary Tagliaferri reviewed the Phase 2b REZOLVE-AA design: 92 adult patients were randomized to subcutaneous rezpeg 24 mcg/kg every two weeks, rezpeg 18 mcg/kg every two weeks, or placebo. The initial 36-week induction period results were previously reported in December, she said.

Tagliaferri emphasized the 16-week blinded extension was designed differently than a typical maintenance phase. “The alopecia areata study selected for the non-responders to continue treatment,” she said, with the goal of determining whether continuing dosing beyond 36 weeks could increase the number of patients achieving SALT ≤20. Patients who had already reached SALT ≤20 by week 36 were not eligible to continue dosing in the extension, though Tagliaferri noted one placebo patient advanced to the extension after an investigator requested special dispensation while remaining blinded.

According to Tagliaferri, 31 patients with SALT >20 at week 36 entered the extension (13 on 24 mcg/kg, 14 on 18 mcg/kg, and four on placebo), and 94% completed treatment to week 52.

Key 52-week efficacy readouts and safety overview

Tagliaferri said the extension data showed “deepening of responses” among those continuing treatment. Among the 31 extension participants, she reported that at the end of 36 weeks, 4% achieved a 75% or greater reduction in baseline SALT score, rising to 26% after 52 weeks of treatment.

In the extension population, Tagliaferri reported eight new SALT ≤20 responders among 27 patients receiving rezpeg (four in each dose group), with 29% of patients in the 18 mcg/kg arm and 31% in the 24 mcg/kg arm achieving new SALT ≤20 responses during weeks 36 to 52; there were no new SALT ≤20 responses in the placebo arm.

Across the full study population, she said the SALT ≤20 response rate increased from 15.6% at week 36 to 27.6% at week 52 with additional treatment, and that the high dose versus placebo comparison reached statistical significance with a p-value of 0.049. She also said “no patient who achieved a SALT 20 score or better in the 36-week induction period relapsed while on treatment.”

Tagliaferri also discussed other exploratory endpoints, including SALT ≤30 (representing at least 70% scalp hair coverage). She said the high-dose cohort’s SALT ≤30 response rate increased from 29% at week 36 to 35% at week 52 and was statistically significant compared with placebo.

On safety, Tagliaferri said the 52-week dataset represents the longest twice-monthly dosing duration studied in the rezpeg program and that there were “no new safety findings.” She said no patients discontinued during the 16-week extension due to an adverse event, and “nearly all AEs were mild to moderate in severity and self-resolve.” She added that the injection-site reaction (ISR) profile was consistent with prior studies, with a median time to resolution of five days, and noted no indications of increased risks for a range of adverse events she listed, including thromboembolic and malignancy signals. She also said rezpeg’s known adverse event profile “should not require the extensive laboratory testing or monitoring typically associated with JAK inhibitors.”

Physician panel: adoption expectations and Phase 3 considerations

During Q&A, dermatologist and alopecia areata experts discussed how they might use rezpeg if Phase 3 data replicate the findings. Dr. Jonathan Silverberg of George Washington University said that, outside of a small minority of needle-phobic patients, “realistically, 90% or more of my patients” would be started on rezpeg first-line. Dr. David Rosmarin of Indiana University similarly said “90% of my patients” would receive rezpeg first for new starts, citing ongoing concern about boxed warnings on oral JAK inhibitors. Dr. Benjamin Ungar of the Icahn School of Medicine said he expects a “very high proportion” of patients would start on rezpeg and highlighted interest in longer-term questions such as dosing interval and durability.

On upcoming milestones, Tagliaferri said Nektar plans an end-of-Phase 2 meeting with the FDA in the second quarter to align on Phase 3 registrational strategy in alopecia areata, and expects to report blinded 24-week off-treatment follow-up data from REZOLVE-AA in the fourth quarter to help inform maintenance dosing and long-term extension design.

About Nektar Therapeutics NASDAQ: NKTR

Nektar Therapeutics NASDAQ: NKTR is a biopharmaceutical company dedicated to discovering and developing novel drug candidates through its proprietary chemistry and immunology platforms. The company focuses on polymer conjugate technology, which enables the creation of longer-acting versions of existing drugs, and on T-cell modulatory therapies aimed at harnessing the body's immune system to treat cancer and other serious diseases.

Nektar's product portfolio and pipeline include a range of clinical-stage and partnered programs.

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