Jonathan Silverberg, MD, PhD, MPH

On June 24, 2025, Nektar Therapeutics announced positive results from the 16-week induction phase of its ongoing phase 2b REZOLVE-AD trial, highlighting the efficacy and safety of rezpegaldesleukin, an IL-pathway agonist designed to expand regulatory T cells (Tregs), in adults with moderate-to-severe 

In the study, 393 patients were randomized to receive rezpegaldesleukin at 1 of 3 dosing regimens—24 µg/kg every 2 weeks, 18 µg/kg every 2 weeks, or 24 µg/kg every 4 weeks—or placebo every 2 weeks. Patients who achieved at least 50% improvement in Eczema Area and Severity Index (EASI-50) by week 16 were rerandomized to continue treatment every 4 or 12 weeks in the trial’s maintenance phase.

The trial met its primary endpoint, with all three active treatment arms achieving statistically significant mean improvements in EASI scores from baseline at week 16 compared to placebo (P < .001). Key secondary endpoints were also met across all dose arms, including:

vIGA-AD 0/1 (clear or almost clear skin),

Itch NRS reduction among patients with baseline scores ≥4.

The release from Nektar Therapeutics highlighted the 24 µg/kg every 2 weeks regimen also reached statistical significance for EASI-90 at week 16, with efficacy consistent across patients with vIGA-AD 3 and vIGA-AD 4.

Pharmacodynamic data revealed a dose-dependent increase in circulating Tregs, with the high-dose group showing up to a 6-fold increase at week 16. This observed Treg expansion correlated with reductions in Th2-related inflammatory biomarkers, including TARC/CCL17, IL-19, periostin, and MDC/CCL22, confirming robust biological activity.

“These data show a fast onset of both EASI response and itch relief within the first few doses of rezpegaldesleukin treatment,” said study investigator Jonathan Silverberg, MD, PhD, MPH,professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Science. “This broad-based Treg mechanism may offer a meaningful alternative to other immune-modulating therapies in atopic dermatitis.”

For more on this announcement, check out our interview with Silverberg:

REZOLVE-AD and Rezpegaldesleukin for Atopic Dermatitis, with Jonathan Silverberg, MD, PhD, MPH

Relevant disclosures of interest for Silverberg include AbbVie, lamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer Ingelheim, Bristol-Myers Squibb, and others.

REZOLVE-AD Phase 2b Study of Rezpegaldesleukin Meets Primary and Key Secondary Endpoints in Patients with Moderate-to-Severe Atopic Dermatitis. Nektar Therapeutics. June 24, 2025. Accessed June 25, 2025. 

https://ir.nektar.com/news-releases/news-release-details/rezolve-ad-phase-2b-study-rezpegaldesleukin-meets-primary-and

Videos

Silverberg discussers 16-week data for rezpegaldesleukin in atopic dermatitis from the phase 2b REZOLVE-AD trial.

approved dupilumab (Dupixent) for the treatment of adult patients with bullous pemphigoid, marking the first targeted therapy approved for this chronic, autoimmune 

. The approval, announced by Sanofi and Regeneron, is based on results from the pivotal ADEPT trial and represents the eighth approved indication for dupilumab in diseases driven by type 2 inflammation.

“By addressing two central drivers of the underlying type 2 inflammation that contributes to bullous pemphigoid, Dupixent is the first targeted medicine to allow patients the potential to achieve sustained remission and reduce itch," Alyssa Johnsen, MD, PhD, Global Therapeutic Area Head, Immunology and Oncology Development at Sanofi, said in a statement.1 "This approval in the U.S. is important for the thousands of patients living with bullous pemphigoid, and we look forward to working with regulators around the world to bring this innovative medicine to more patients in need.”

In the 36-week ADEPT trial, 106 adults with moderate-to-severe disease were randomized to receive dupilumab or placebo. Sustained remission was achieved by 18.3% of dupilumab-treated patients versus 6.1% with placebo (difference: 12.2%; 95% CI, –0.8% to 26.1%). Additionally, 38.3% of dupilumab recipients experienced clinically meaningful itch reduction, compared to 10.5% on placebo. Patients on dupilumab also used fewer oral corticosteroids, with a median cumulative dose of 2.8 grams compared to 4.1 grams in the placebo group.

The most common adverse events reported in the trial included joint pain, back pain, edema, upper respiratory infections, and conjunctivitis, with investigators noting the safety profile was consistent with that established in prior trials of dupilumab.

In a recent interview, Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Science, noted the approval as the most impactful news in dermatology for the first half of 2025. For more on the importance of the approval for dupilumab in bulls pemphigoid, check out our interview with Silverberg below:

Dupilumab in Bullous Pemphigoid Represents Leap Forward for Dermatology, with Jonathan Silverberg, MD, PhD, MPH

Relevant disclosures of interest for Silverberg include AbbVie, lamar, Aldena, Amgen, AObiome, Arcutis, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, and others.

Regeneron Pharmaceuticals Inc. Dupixent® (dupilumab) Approved in the U.S. as the Only Targeted Medicine to Treat Patients with Bullous Pemphigoid (BP) | Regeneron Pharmaceuticals Inc. Regeneron Pharmaceuticals Inc. Published June 20, 2025. Accessed June 20, 2025. 

https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-approved-us-only-targeted-medicine-treat

Silverberg discusses the significance of the dupilumab approval in BP and why he thinks it's the most important news in dermatology in 2025 so far.

025 Revolutionizing Atopic Dermatitis (RAD) Conference

 in Nashville, TN, a presentation titled ‘Recent Approvals in [Atopic Dermatitis] Therapy’ was given to attendees to highlight decisions in the atopic dermatitis space by the 

One presenter of this talk on recent atopic dermatitis approvals by the FDA was Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Science. Silverberg spoke with 

 in a new Q&A interview on this topic and on related research. The interview is listed below:

 In your talk ‘Recent Approvals in AD Therapy,’ what are some of the most notable takeaways regarding FDA approvals for atopic dermatitis covered in this session?

I just presented on recent atopic dermatitis approvals, particularly focusing on biologic and systemic therapies. We have 2 new therapies that were just approved in the past 12 months, which are nemolizumab and lebrikizumab as biologics. So I took a deep dive into both of those drugs and my own clinical pearls, as well as some thoughts about where and how to use them.

I also threw an update on data that we have now or recent data that we have for dupilumab as well as the oral JAK inhibitors, because we've had a lot of new insights, even though, technically, they're a little bit older therapies.

 With upcoming therapeutic research in atopic dermatitis, are there any drugs not approved yet which you are looking forward to?

Yeah, the pipeline for atopic dermatitis therapies is enormous right now, and it's really cool. There's a lot of stuff being tested with a lot of novel technologies. I think long-term, the bispecifics or multi-specific biologics are really cool. The ability to hit multiple targets simultaneously [is great], but without the off-target effects.

We're seeing all kinds of novel pathways being probed in atopic dermatitis, OX40 and 40 ligand, interleukin-18, interleukin-22 receptor. And we're not sure where all these are going to go. But these are really exciting and pushing the boundaries of science and the disease.

 Outside of atopic dermatitis, what are you looking forward to in terms of dermatology research?

I think there's a tremendous need, outside of atopic dermatitis and broadly-speaking within dermatology, for better diagnostics and better biomarkers. I think our classification system that we use in dermatology, while over 100 years old, and while we have great, skilled clinical dermatologists doing it, really needs to be brought into the modern era. We really need to have better prognostic tools, theranostic tools, and diagnostic tools across the variety of our different immune mediated diseases and just chronic inflammatory skin disorders.

You are the founder of RAD. What message would you share with colleagues, clinicians, and attendees?

 RAD was created to address this amazing increase in knowledge and treatment options that we have now for atopic dermatitis. It's hard for the clinician who's busy in the trenches to keep up with all the data and to really gain insights into all these new therapies that kind of hit us at once and are still coming really fast and furious.

How do we where should we use them? When should we use them? How do we keep up with all that? RAD is here to provide both cutting edge perspectives as well as that evidence-based approach, knowing that you're getting the top quality information all in a one-stop shop.

To find out more from Silverberg and other experts in the field of dermatology, view our 

The quotes used in this Q&A interview were edited for the purposes of clarity.

Articles

The 2025 Revolutionizing Atopic Dermatitis (RAD) Conference in Nashville featured a presentation on recent FDA approvals in atopic dermatitis therapy, focusing on biologic and systemic treatments. Jonathan Silverberg, MD, PhD, MPH, highlighted new therapies, including nemolizumab and lebrikizumab, and discussed updates on dupilumab and oral JAK inhibitors. He emphasized the promising pipeline of novel therapies targeting multiple pathways. Silverberg also stressed the need for improved diagnostics and biomarkers in dermatology. RAD aims to provide clinicians with cutting-edge, evidence-based insights into emerging treatments.

In this Q&A interview, Silverberg highlighted takeaways from his talk at RAD 2025 on recent FDA approvals for atopic dermatitis.

Recent FDA Approvals for Atopic Dermatitis, with Jonathan Silverberg, MD, PhD, MPH

Emerging Treatments for Atopic Dermatitis

Video content above is prompted by the following:

Are there any ongoing atopic dermatitis studies or emerging therapies that you are excited about?

What advice would you like to share with clinicians taking care of patients with moderate/severe atopic dermatitis?

Recent advancements in atopic dermatitis research have focused on novel therapies and ongoing clinical trials. Emerging treatments, such as biologics and small molecules, are showing promise in managing moderate to severe cases. Clinicians are advised to stay informed about these developments to optimize patient care. Emphasizing a personalized approach, considering patient-specific factors, and maintaining open communication with patients are crucial. Additionally, integrating new therapies with existing treatment regimens can enhance outcomes. Continuous education and collaboration with specialists are essential for improving management strategies in atopic dermatitis.

Looking to the future of atopic dermatitis treatment, the panel discusses ongoing research and promising emerging therapies. 