Derms on Drugs: Best of AAD 2025 – The Hottest of the Hot Dermatology Data

Podcast: Derms on Drugs
Host: Scholars in Medicine
Date: March 28, 2025
Featuring: Dr. Matt Zirwas (A), Dr. Laura Ferris (B), Dr. Tim Patton (C)

Episode Overview

In this high-energy, post-American Academy of Dermatology (AAD) conference episode, the three dermatologist hosts dissect their favorite late-breaking research unveiled at AAD 2025. With a tone mixing camaraderie, irreverence, and genuine clinical expertise, Matt Zirwas, Laura Ferris, and Tim Patton trade takes on the hottest data, speculate on future practice-changing treatment advances, and riff on comical moments only derm docs can appreciate. The focus: game-changing therapeutics in psoriasis, lupus, atopic dermatitis, new mechanisms of action for challenging diseases, and digital health innovations.

Key Research Highlights and Discussions

1. ICOTRA Kinra – A Promising Oral IL-23 Receptor Peptide for Psoriasis

Presented by: Laura Ferris
[01:16–03:59]

• Study: Phase 3, 200 mg once daily oral peptide, ICOTRA kinra, targeting the IL-23 receptor in moderate-to-severe psoriasis.
• Population: Mostly adults; ~33% bio-experienced; mean BSA ~25%.
• Results:
  • PASI 90: 50% at week 16; 65% at week 24
  • PASI 100: 27% at week 16; 40% at week 24
  • IGA 0/1: 65% at week 16; 74% at week 24
  • Scalp-specific IGA 0/1: 80% of affected patients at week 24
  • Safety: No new signals
• Comparison: Efficacy similar to Cosentyx (secukinumab) but slower onset; potential major upside is daily oral dosing.
• Quote:
  • “I think it's going to be interesting to see how this works in special sites, psoriatic arthritis, all kinds of stuff... it does seem like it worked as well as BID dosing, which I think is going to be important for an oral drug.” – Laura Ferris [02:39]
  • “You would say this looks like Cosentyx, but slower. But it's once a day oral.” – Laura Ferris [03:47]

2. Dukravacitinib for Cutaneous Lupus Erythematosus (CLE): Paisley CLE Study

Discussed by: Tim Patton
[04:06–06:24]

• Study: Global phase II, oral Tyk2 inhibitor (dukravacitinib), randomized against placebo for CLE.
• Primary Endpoint: Mean percent change from baseline in CLASI-A at week 16
• Results:
  • Placebo: 28.4% change
  • Dukra 3mg BID: 47%
  • Dukra 6mg: 50%
  • CLASI-70: Placebo 15.9%; Dukra 3mg BID 49.5%; Dukra 6mg lower (statistically non-significant, p=0.273)
• Meta-Analysis Reference: Dukra atop small molecule/biologic landscape for lupus (with caveats).
• Quotes:
  • “That's a huge difference. The higher dose Duker percentage was lower...that 70 data was weird, but overall looks like Dukra could be a good option for CLE patients.” – Tim Patton [05:24]
  • On mechanism:
    “It hits the interferon alpha pathway, right? So it totally makes sense for lupus. And...the pictures are pretty impressive.” – Laura Ferris [06:40]

3. QY201 – Dual JAK1/Tyk2 Inhibitor for Atopic Dermatitis

Presented by: Matt Zirwas
[07:00–09:28]

• Study: Phase 2 dose finding, 12-week trial, dual JAK1/Tyk2 inhibitor (QY201) vs. placebo in moderate–severe atopic dermatitis.
• Results (Highest Dose – 20mg BID):

  • 80% achieved EASI-75 at 12 weeks (noted as “by far the best I've ever seen”)

  • IGA 0/1: 70% (historically, high dose Rinvoq ~50–60%)
• Implications: If phase III confirms, QY201 may become the most effective oral agent for AD; contemplating use of combo JAK1+Tyk2 inhibition even now for toughest cases.
• Quotes:
  • “If these results are reproducible...it would be the most effective thing we've got.” – Matt Zirwas [07:43]
  • “Maybe that’ll also work in things like lupus...I think we’re just seeing the tip of the iceberg…” – Laura Ferris [08:59]

4. Next-Gen Tyk2 Inhibitors in Plaque Psoriasis

Summarized by: Laura Ferris
[09:33–12:59]

4.1. ESK001

• Claimed to provide “24-hour full inhibition” of Tyk2 (vs. partial for Sotyktu); 40mg BID
• At 12 weeks: PASI 75 – 64%
• At 52 weeks (open label): PASI 75 – 77.5%; PASI 90 – 61%; PASI 100 – 39%
• Comparison: “Better PASI 90 and 100 than Sotyktu.”

4.2. D2570 (Invent Bio, China)

• PASI 75 up to 90%; PASI 90 70–77%; PASI 100 39–50%

4.3. ICP488 (Iknowcare, China)

• PASI 75 – 78%; PASI 90 – 35–50%; PASI 100 – 11%

• Key Commentary:

  • “It’s hard to know...maybe one is less selective, or more selective, bioavailability...who knows?” – Laura Ferris [12:10]
  • “It’ll be an interesting race. Hopefully it’s not a race to the bottom—hopefully it’s finish line.” – Matt Zirwas [12:59]

5. Dupilumab in Bullous Pemphigoid (BP): LIBERTY-BP ADEPT Phase 2/3

Presented by: Tim Patton
[13:18–17:54]

• Trial Design: Double-blind, placebo-controlled, 52 weeks, Dupilumab (+steroid taper) in moderate–severe BP.
• Primary Endpoint: Sustained remission at week 36 – 20% on Dupilumab vs. 4% placebo (a tough composite endpoint).
• Clinical Pearls:
  • Cumulative steroid dose on Dupilumab group was 1678mg less (approx. 6.6mg/day reduction over 36 weeks)
  • Discuss clinical challenge: “How do we get them off steroids?”
• Quotes:
  • “If 80% of the patients are still on steroids, did you really, like, get you to your main goal?...but Doopy's easier to administer. Side effect profile is nice. I think more people will use it.” – Tim Patton [15:42]
  • “It’ll be the Otezla of BP…or maybe [biomarkers] will define which patients do best.” – Matt Zirwas [17:54]

6. Digital Health Innovation: Patient-Led, AI-Assisted Patch Testing

Presented by: Matt Zirwas
[18:03–21:54]

• New Protocol: Patients use an app to select allergens and apply only 20 allergens (10 on each forearm instead of traditional 80–100 on the back).
• Follow-up: AI visual reading after two days assesses reactions.
• Clinical Impact: Could vastly simplify patch testing logistics, making screening more accessible.
• Technical Note: Studies suggest volar forearm is a reliable site vs. back for application.
• Quotes:
  • “This could be a really big breakthrough…you could literally be like, ‘Hey, put this app on your phone, do the stuff…come back…we’ll put the tests on and go on your way.’” – Matt Zirwas [19:41]
  • On high “propolis” positives:
    “I never saw clinical relevance to it…clearly a reaction…but I never saw the people get better.” – Matt Zirwas [20:48]

7. Laser-Assisted Drug Delivery for Non-Melanoma Skin Cancer

Presented by: Laura Ferris
[21:54–24:39]

• Study Design: Small single-center, non-randomized; dual-wavelength non-ablative laser, then topical tirbanibulin (Klisyri) for basal and squamous cell carcinomas <2cm.
• Treatment: In-office application followed by 4 nights at home; follow-up 1, 6, 12 months.
• Results: 100% response rate (low-risk tumors, good cosmetic outcomes)
• Critique: Lack of controls—should have tested laser alone, drug alone, combination.
• Quotes:
  • “Maybe there are ways that we can deliver drugs…more creatively… deserves more work. Kudos to people in training doing clinical trials up against big pharma.” – Laura Ferris [23:46]

8. Intacel PH762: Intratumoral siRNA for Skin Cancer

Presented by: Tim Patton
[24:58–26:34]

• What is it? Intacel PH762 is an siRNA targeting PD-1 in T cells—functions like a “cellular PD-1 inhibitor.”
• Protocol: Four intratumoral injections in 3 weeks, then excision; small numbers so far (6 patients).
• Results: 2 complete responses, 2 partial, 2 non-responders among SCC patients; 1 metastatic melanoma patient no response.
• Quotes:
  • “Just a neat molecule…I don't think we have any big intratumoral data out of the PD1s or anything like that to see how these numbers compare.” – Tim Patton [26:34]

9. Novel Immunobiologics for Alopecia Areata & Atopic Dermatitis

9.1. Icabart – Dual IL-7/TSLP Blockade for Severe Alopecia Areata

Presented by: Matt Zirwas
[27:42–31:43]

• Mechanism: Monoclonal antibody blocks both IL-7 and TSLP receptors, potentially “turns off” autoimmune T cells sparing normal immunity.
• Study: Small phase 2a; hard-to-enroll as many switched to JAK inhibitors.
• Findings: “Some kept regrowing hair for 6 months after the end of the study,” suggesting durable immune reset.
• Quotes:
  • “This could be our first biologic for alopecia areata…it could be something that really has a long-term effect…like turning around this autoimmune process.” – Matt Zirwas [28:49]

9.2. Rocatinlumab – OX40 Antagonist for Atopic Dermatitis

Presented by: Matt Zirwas
[29:37–31:43]

• Mechanism: Blocks OX40, depleting pathogenic memory T cells for potential disease modification.
• Results: Eczema study—EASI-75 (33% at 24 weeks); lower than expected efficacy but key is potential for long-term remission and disease course alteration.
• Side Effects: 20% had severe flu-like reaction after first dose (“I wonder if that's a marker for efficacy...”)
• Quotes:
  • “Main benefit doesn’t seem to be rapid efficacy—it seems to be potential for long-term remission is the big takeaway.” – Matt Zirwas [31:43]

Notable Quotes & Memorable Moments

Skewering Conference Norms & Each Other

• “Not a nerd like Ferris.” – Matt Zirwas [15:29]
• “It’s very odd looking. I don’t know, it’s dystopian to me. Everyone’s...” – Tim Patton, on people snapping slides at conferences [15:34]
• “She was actually just trying to give you smallpox.” – Laura Ferris, joking about Matt’s mom’s vaccination paranoia [24:51]
• “Measles coming back. Smallpox is probably gonna come back.” – Tim Patton, deadpan [24:39]

On Dermatology Therapeutics

• “It’ll be an interesting race. Hopefully it’s not a race to the bottom—hopefully it’s finish line.” – Matt Zirwas, on the Tyk2 inhibitor pipeline [12:59]
• “It’ll be the Otezla of BP…or maybe [biomarkers] will define which patients do best.” – Matt Zirwas [17:54]

Segment Timestamps

| Segment | Start – End | |--------------------------------------------|----------------| | Welcome & Overview | 00:12 – 01:16 | | Oral ICOTRA kinra for Psoriasis | 01:16 – 03:59 | | Dukravacitinib for Cutaneous Lupus | 04:06 – 06:24 | | QY201 Dual JAK1/Tyk2 for Atopic Derm | 07:00 – 09:28 | | Next-gen Tyk2 inhibitors (ESK001, others) | 09:33 – 12:59 | | Dupilumab in BP (LIBERTY-BP) | 13:18 – 17:54 | | AI-Assisted Patch Testing | 18:03 – 21:54 | | Laser-assisted Drug Delivery for NMSC | 21:54 – 24:39 | | Intacel PH762 siRNA for Skin Cancers | 24:58 – 26:34 | | Icabart for Alopecia Areata | 27:42 – 31:43 | | Rocatinlumab (OX40) for Atopic Derm | 29:37 – 31:43 | | Closing & Sign-Off | 32:33 – 33:07 |

Final Thoughts

The “Best of AAD 2025” episode delivers a whirlwind review of transformative research—from new oral and biologic drugs poised to upend entrenched therapies, to clever digital health and drug delivery innovations. Equally valuable are the candid appraisals of trial results, recognition of real-world caveats, and speculation on what future game-changers may finally tip the balance for stubborn diseases. For clinicians and trainees hungry for the next big dermatologic breakthrough—or just keen to savor expert banter with a side of comic relief—this episode is a blueprint for what’s next in dermatology.