New Treatments and Breakthroughs in Dermatology: Key Highlights From Maui Derm NP+PA Fall

George Martin, MD, founder of the Maui Derm meeting, and Ted Rosen, MD, of Baylor College of Medicine, joined forces once again to deliver the now-signature new products and therapies update at Maui Derm NP+PA Fall 2024 meeting, held September 15-18, 2024, in Nashville, Tennessee.

The pair provided a rundown of recently approved therapies for various disease states within dermatology and included a sneak peek at what’s in the pipeline. Here are the key takeaways from their session:

Acne

For acne, providers now have a triple combination treatment available in the form of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide (BPO). But how does it compare to a 2-drug combination (BPO/adapalene gel, clindamycin/adapalene gel, or clindamycin/BPO gel)? Phase 2 studies have shown that more than 50% of patients treated with the triple combination IDP-126 gel achieved treatment success (defined as at least a 2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 [clear] or 1 [almost clear]) compared with 2-drug regimens.

Atopic Dermatitis

Currently, there’s a healthy topical armamentarium for mild-to-moderate atopic dermatitis (AD) and it continues to grow with the July 2024 approval of roflumilast 0.15% for patients 6 years and older. Also currently approved for psoriasis (0.3% cream) and seborrheic dermatitis (0.3% foam), the PDE-4 inhibitor continues to be studied for vitiligo.

Providers also expect an approval before end-of-year for tapinarof for moderate-to-severe AD in patients 2 years and older. The 1% cream formulation is applied every day and is ideal for continuous use. The data, according to Rosen and Martin, are excellent. In the ADORING phase 3 program, greater than 55% of patients treated with the study drug achieved at least 75% improvement in Eczema Area and Severity Index (EASI) scores by week 8. There is an understood incidence of follicular events when on the drug (in 10% of patients in the ADORING trials) but it is not enough to deter use.

Other current or upcoming options for AD include:

1. Crisaborole: Approved as a once-a-day treatment that works as a long-term solution, it may sting or burn at first with application but it goes away with repeated use, Rosen says.
2. Ruxolitinib: This topical JAK inhibitor “is going to be a go-to” in patients aged 2 to 6 and 7 to 12, Rosen says. It has a very good safety profile and boasts “dramatic” efficacy, Martin added.
3. Delgocitinib: Not yet approved, this topical pan-JAK inhibitor has been studied in moderate-to-severe chronic hand dermatitis in the phase 3 DELTA 2 trial. That study compared the twice-a-day application of delgocitinib cream with vehicle for 16 weeks (and then a 36-week open-label extension). The primary end point was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) score of 0/1 with 2-grade improvement at week 16. Ultimately, a greater percentage of patients who received the study drug had IGA-CHE treatment success (29.1%) versus vehicle (6.9%) (P = 0.001).
4. Upadacitinib versus dupilumab: The Level Up study pitted upadacitinib head-to-head against dupilumab in adults with moderate-to-severe AD. An initial regimen of upadacitinib 15 mg escalated to 30 mg demonstrated superiority over dupilumab in terms of the primary end point (achievement of EASI 90 and WP-NRS 0/1 at week 16), as well as all secondary end points. The other upside of upadacitnib, Rosen pointed out, is that it is a pill versus an injection, and patients tend to prefer pill formulations.
5. Monoclonal antibodies and oral systemics: “As we move forward in dermatology, JAKs should replace systemic and topical steroids in your armamentarium,” Martin said. “They're safer than steroids, both topically and systemically.”

Tralokinumab is another IL-13 monoclonal antibody approved for AD in adolescents aged 12 to 17 years. This one really selectively targets IL-13 and, in adolescents, is initiated with a loading dose of 300 mg, followed by a 150-mg dose every 2 weeks. For adults aged 18 and older, the loading dose is 600 mg, followed by a 300-mg dose every 2 weeks. That frequency can be extended to every 4 weeks in adults at 16 weeks granted they are recording IGA scores of 0/1 and weigh less than 220 pounds.

A very recent addition to the AD armamentarium is lebrikizumab, which was approved September 13, 2024, for moderate-to-severe AD all the way down to age 12. IGA scores 0/1 and EASI 75 and 90 levels are the “highest we have seen for a biologic,” Rosen and Martin said, but there have been no comparator trials yet. It is initiated with a 500-mg loading dose (given as 2 separate 250-mg pre-filled syringes administered at weeks 0 and 2), followed by 250 mg every 2 weeks until 16 weeks, at which point doses can be stretched to every 4 weeks given adequate clinical response.

Conjunctivitis is still a concern with this class of medication, and it makes sense why, Martin explained, because the ocular surface is an epithelium the same way your skin is. The conjunctivitis is managed in the vast majority of patients and doesn’t cause any major issues.

Another AD treatment awaiting approval is nemokizumab, which is currently approved for patients 18 years or older with prurigo nodularis. This drug is unique because it is an IL-31 receptor antibody. Its signaling actually triggers nerve elongation and branching, which decreases itch. Contrary to what many believe, these non-histamine sensory neurons are the key drivers of itch, which explains why patients never really respond to antihistamines.

“Do we have a comparator trial against tralokinumab, dupilumab, and now lebrikizumab?” Martin asked. “No, but understand that this is also going to be a player in itch, and we're going to have to get experience with this and ferret out which type of patient is going to respond best.”

Lastly is the OX40 and OX40L inhibitors, a new group of drugs that enhance T-cell activity and the production of cytokines that can contribute to or augment AD activity. Two drugs, rocatinlimab and amlitelimab, are currently under investigation in phase 2 trials and, so far, the efficacy and safety look good, with no hypersensitivity reported. Interestingly, this class of molecule actually blocks the development of resident memory T cells.

“So when you stop [the drug], there's no resident memory T cells in the dermis to keep driving the disease, and that's why you have these incredibly long sustained remissions,” Martin explained.

Hidradenitis Suppurativa

Providers now have an FDA-approved option for hidradenitis suppurativa (HS) in the form of IL-17A antagonist secukinumab. The metric used in clinical trials for HS therapies is Hidradenitis Suppurativa Clinical Response (HiSCR) 50, which means > 50% reduction in abscess and inflammatory nodules compared with baseline, as well as no increase in the number of abscesses or number of draining fistulas compared with baseline.

In the SUNSHINE and SUNRISE phase 3 trials of secukinumab for HS, 71% of participants had a > 50% improvement in abscesses and inflammatory nodules compared with baseline while 83% had np new draining tunnels. In SUNRISE, 78% of participants experienced zero HS flares, and the 70% who started the trial reporting moderate-to-severe pain reported mild or no pain after treatment.

Patients with HS should be initiated with a 300-mg loading dose of secukinumab at weeks 0, 1, 2, 3, and 4, followed by 300 mg every 4 weeks after. Providers can consider increasing the dosage to 300 mg every 2 weeks after the loading dose for patients who are not responding, Rosen and Martin advised.

Bimekizumab for HS is currently being studied in phase 3 trials, where it is demonstrating positive efficacy and durable response.

Chronic Spontaneous Urticaria

Currently, there is 1 approved and 2 pending treatment options for chronic spontaneous urticaria (CSU), which is characterized by the presence of wheals and angioedema that persist for at least 6 weeks. Martin explained that the management of CSU has bounced between dermatology providers and allergists in the past but is swinging back toward the dermatology realm as of late.

Many providers are concerned by the presence of angioedema and fear anaphylaxis, but Martin says that one is not indicative of the other. “According to the urticaria gurus, 37% of the patients who have urticaria also have angioedema, and 6% just have angioedema. That’s what’s been published,” he said. “In my experience, it’s not quite that high, not quite that common, but just keep in mind it doesn’t mean they’re going to stop breathing [or] won’t be able to swallow.”

Omalizumab is a monoclonal antibody that was approved for CSU in 2014. Besides that, phase 3 trials of dupilumab and remibrutinib have concluded. The FDA requested additional scientific data on dupilumab for CSU, but Rosen and Martin believe it will ultimately receive approval. The drug significantly reduced both itch and the presence of hives in patients involved in the LIBERTY-CSU CUPID phase 3 trials.

Remibrutinib is another future option for CSU. This drug is an oral BTK inhibitor offered in pill form. The dosing is 25 mg twice a day, and it met all primary and secondary end points in the phase 3 REMIX trials.

Reference:

Rosen T, Martin G. New products and new therapies. Presented at: Maui Derm NP+PA Fall; September 15-18, 2024; Nashville, Tennessee.