Nektar Therapeutics Announces Completion of Target Enrollment in REZOLVE-AD Phase 2b Clinical Trial of Rezpegaldesleukin in Patients with Moderate-to-Severe Atopic Dermatitis

Rhea-AI Summary

Nektar Therapeutics (NKTR) has completed target enrollment in its REZOLVE-AD Phase 2b study of rezpegaldesleukin for moderate-to-severe atopic dermatitis. The 396-patient trial, initiated in October 2023, reached full enrollment in just 14 months across approximately 110 global sites.

The study focuses on patients who haven't previously received biologic or JAK inhibitor therapies. Participants are randomized across three dose regimens or placebo for a 16-week induction treatment period. The primary endpoint measures improvement in EASI score, with secondary endpoints including vIGA-AD, EASI-75, and Itch NRS improvements.

Geographic distribution of enrollment includes: 67% in European countries, 17% in the United States, 11% in Canada, and 5% in Australia. Previous clinical trials demonstrated that rezpegaldesleukin safely increased Tregs and improved disease outcomes, with effects lasting up to 36 weeks post-treatment.

Positive

• Completed enrollment target of 396 patients ahead of schedule in 14 months
• Strong patient and physician interest in the trial
• Previous trials showed promising durability of treatment effects up to 36 weeks
• Large market potential with less than 10% of 30 million eligible patients currently receiving biologics

Negative

• Topline data won't be available until Q2 2025
• Treatment requires ongoing maintenance therapy

Insights

Clinical Research Analyst

The completion of target enrollment in REZOLVE-AD Phase 2b trial represents a significant milestone for Nektar's rezpegaldesleukin program. The 396-patient study achieved enrollment in just 14 months, indicating strong interest from both physicians and patients. The trial's design is particularly robust with its multi-regional approach spanning Europe (67%), US (17%), Canada (11%) and Australia (5%).

The study's focus on treatment-naïve patients (no prior biologics/JAK inhibitors) is strategically important, as it targets the 90% of eligible patients not currently receiving biological treatments. The trial's comprehensive endpoint structure, including EASI score improvement, vIGA-AD, EASI-75 and Itch NRS, will provide valuable efficacy data across multiple clinically relevant measures.

Key differentiators include the novel IL-2R agonist mechanism and the potential for durable response up to 36 weeks post-treatment cessation, which could represent a significant advantage over existing therapies. The maintenance phase design, comparing monthly versus quarterly dosing, could establish optimal treatment protocols for long-term management.

Market Research Analyst

From a market perspective, this development is particularly compelling given the substantial untapped market in atopic dermatitis treatment. With only 10% of 30 million eligible patients currently receiving biologics in the US and Europe, there's significant room for market penetration. The rapid enrollment pace suggests strong market demand and physician buy-in for novel treatment mechanisms.

The trial's strategic patient selection criteria and global site distribution enhance the commercial viability of the results. The focus on moderate-to-severe cases, coupled with the exclusion of biologic-experienced patients, positions rezpegaldesleukin to potentially capture a significant portion of the first-line biologic treatment market.

The Q2 2025 timeline for topline data readout could position Nektar well in the competitive landscape, especially if the durability advantage is confirmed. For a company with a market cap of $210 million, positive trial results could significantly impact valuation, particularly given the large addressable market and current treatment gaps.

SAN FRANCISCO, Jan. 10, 2025 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced the company has completed target enrollment in its REZOLVE-AD Phase 2b study of rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis.

Rezpegaldesleukin is a first-in-class interleukin-2 receptor (IL-2R) agonist that proliferates and activates regulatory T cells (Tregs) with promising dose-dependent clinical activity in multiple skin disease settings. Results from multiple clinical trials showed that rezpegaldesleukin safely and dose-dependently increased Tregs and rapidly improved measurable exploratory disease outcomes in patients with moderate-to-severe atopic dermatitis that were largely durable for at least 36 weeks after ceasing treatment, demonstrating proof-of-concept in this indication.¹ Proof-of-concept efficacy and safety data from a Phase 1b study of rezpegaldesleukin in atopic dermatitis patients were presented at the 2023 EADV Congress in October 2023 (Presentation Link).

"We are pleased to announce that we reached our target enrollment for our 396-patient Phase 2b trial of rezpegaldesleukin," said Howard W. Robin, President and CEO of Nektar Therapeutics. "We are grateful to the patients and physicians whose strong interest in this novel mechanism, together with the proof-of-concept clinical data, led to completing enrollment of the study in just 14 months. Less than 10% of the 30 million atopic dermatitis patients who can receive biologics in the US and Europe are currently receiving treatment and we believe that novel mechanisms are key to helping more patients with this chronic and serious skin disorder. We look forward to announcing the topline data from the 16-week induction treatment period in this study in the second quarter of 2025."

The REZOLVE-AD (NCT06136741) study enrolled patients with moderate-to-severe atopic dermatitis who had not previously received treatment with biologic or JAK inhibitor therapies. Patients were randomized across three different dose regimens of rezpegaldesleukin or placebo for a 16-week induction treatment period. Following this period, patients who meet an Eczema Area and Severity Index (EASI) score threshold for advancement to maintenance are re-randomized to one of two maintenance regimens at their original dose level to receive maintenance therapy either once a month or once every three months.

The primary endpoint of the Phase 2b study is mean improvement in EASI score at the end of the 16-week induction treatment period. Secondary endpoints include the proportion of patients achieving Validated Investigator Global Assessment (vIGA-AD) of 0 or 1, those achieving EASI-75, and those achieving a greater than or equal to a 4-point improvement in Itch Numeric Rating Scale (NRS).

This trial was initiated in October 2023. Patients were enrolled across approximately 110 sites globally with: 67% enrolled in the European countries of Poland, Bulgaria, Germany, Czechia, Spain, Croatia and Hungary; 17% enrolled in the United States; 11% enrolled in Canada; and 5% enrolled in Australia. Patient randomization was stratified based on baseline disease severity measured by vIGA-AD and geographic region.

Enrollment criteria in the study included a minimum EASI score of 16.0, a minimum Body Surface Area (BSA) of 10% and a minimum vIGA-AD of 3 at both screening and randomization. Patients who experienced an unstable course of atopic dermatitis between screening and randomization per investigator assessment were excluded from the study.

About Rezpegaldesleukin

Autoimmune and inflammatory diseases cause the immune system to mistakenly attack and damage healthy cells in a person's body. A failure of the body's self-tolerance mechanisms enables the formation of the pathogenic T lymphocytes that conduct this attack. Rezpegaldesleukin is a potential first-in-class resolution therapeutic that may address this underlying immune system imbalance in people with many autoimmune and inflammatory conditions. It targets the interleukin-2 receptor complex in the body in order to stimulate proliferation of powerful inhibitory immune cells known as regulatory T cells. By activating these cells, rezpegaldesleukin may act to bring the immune system back into balance.

Rezpegaldesleukin is being developed as a self-administered injection for a number of autoimmune and inflammatory diseases. In addition to the REZOLVE-AD study, it is also being evaluated in the REZOLVE-AA study, a randomized, double blind, placebo-controlled Phase 2b clinical trial for treatment of patients with severe-to-very-severe alopecia areata (NCT06340360). Rezpegaldesleukin is wholly-owned by Nektar Therapeutics.

About Atopic Dermatitis

Atopic Dermatitis is the most common type of eczema, affecting approximately 30 million people in the United States.² AD is characterized by a defect in the skin barrier, which allows allergens and other irritants to enter the skin, leading to an immune reaction and inflammation.

About Nektar Therapeutics

Nektar Therapeutics is a clinical-stage biotechnology company focused on developing treatments that address the underlying immunological dysfunction in autoimmune and chronic inflammatory diseases. Nektar's lead product candidate, rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class regulatory T cell stimulator being evaluated in two Phase 2b clinical trials, one in atopic dermatitis and one in alopecia areata. Nektar's pipeline also includes a preclinical bivalent tumor necrosis factor receptor type II (TNFR2) antibody and bispecific programs, NKTR-0165 and NKTR-0166, and a modified hematopoietic colony stimulating factor (CSF) protein, NKTR-422. Nektar, together with various partners, is also evaluating NKTR-255, an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer, in several ongoing clinical trials. Nektar is headquartered in San Francisco, California. For further information, visit www.nektar.com and follow Nektar on LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements which can be identified by words such as: "will," "announce," "potential," "advance," "anticipate," "can," and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for, rezpegaldesleukin. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of rezpegaldesleukin are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin is an investigational agent and continued research and development for this drug candidate is subject to substantial risks, including negative safety and efficacy findings in future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) rezpegaldesleukin is in clinical development, and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vi) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 8, 2024. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For Investors:

Vivian Wu of Nektar Therapeutics
628-895-0661

For Media:

Madelin Hawtin
LifeSci Communications
603-714-2638
mhawtin@lifescicomms.com

1. Silverberg, J.I., Rosmarin, D., Chovatiya, R. et al. The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials. Nat Commun 15, 9230 (2024). https://doi.org/10.1038/s41467-024-53384-1
2. Hanifin, J. M., Reed, M. L. & Eczema Prevalence and Impact Working Group. A population-based survey of eczema prevalence in the United States. Dermatitis 18, 82–91 (2007).

 

View original content to download multimedia:https://www.prnewswire.com/news-releases/nektar-therapeutics-announces-completion-of-target-enrollment-in-rezolve-ad-phase-2b-clinical-trial-of-rezpegaldesleukin-in-patients-with-moderate-to-severe-atopic-dermatitis-302347728.html

SOURCE Nektar Therapeutics

FAQ

When will Nektar (NKTR) release topline data for the REZOLVE-AD Phase 2b trial?

Nektar plans to announce topline data from the 16-week induction treatment period in the second quarter of 2025.

How many patients were enrolled in NKTR's REZOLVE-AD Phase 2b trial?

The REZOLVE-AD Phase 2b trial enrolled 396 patients across approximately 110 global sites.

What are the primary endpoints for Nektar's REZOLVE-AD Phase 2b trial?

The primary endpoint is mean improvement in EASI score at the end of the 16-week induction treatment period.

What is the geographic distribution of NKTR's REZOLVE-AD trial enrollment?

The trial enrollment distribution is 67% in European countries, 17% in the United States, 11% in Canada, and 5% in Australia.

How long did previous trials show rezpegaldesleukin's effects could last?

Previous trials showed that treatment effects were largely durable for at least 36 weeks after ceasing treatment.