4 Oral Biologics in Development for Atopic Dermatitis

David Rosmarin, MD

Oral therapy offers patients with chronic disease more flexible regimen options and intermittent treatment capability. It is simplistic, patient-centric, and generally considered the last step of assuring drug adherence in patients who need a daily, weekly, monthly treatment.

In a field exploding with emerging therapy research like atopic dermatitis, oral agents are looked at with particular interest by prescribers and patients alike.

In the second segment of his presentation at the Revolutionizing Atopic Dermatitis (RAD) 2023 Spring Conference in Washington, DC, David Rosmarin, MD, chair of the department of dermatology at Indiana University School of Medicine, highlighted 4 exciting oral biologic therapies under development for the treatment of atopic dermatitis.

CBP-201

An interleukin 4 (IL-4) receptor agonist, CBP-201 has been touted by some as representing the “next generation” of atopic dermatitis treatment due to its higher binding affinity and slower drug elimination. He expressed some doubt on the substantiveness of those claims, though believes “it is a similar medication (to IL-4 inhibitors) and we could definitely use more in this class.”

A trial in China assessed the agent as a 300 mg treatment administered every 2 weeks. At 16 weeks, data showed 30.3% of treated patients achieved Investigators Global Assessment (IGA) scores of 0-1, indicating clear or almost clear skin; 62.9% achieved Eczema Area Severity Index 75% improvement (EASI 75); 35.8% achieved EASI 90; and 35.0% achieved Peak Pruritus Numerical Rating Scale (PP-NRS) scores of ≤4, indicating reduction in itch.

Investigators are considering a 4-week dosing schedule in future use of CBP-201.

Nemolizumab

As an IL-31 receptor agonist, nemolizumab’s mechanism of action has been promoted for its capability to mitigate pruritus, one of the most common and burdensome symptoms of atopic dermatitis.

“A lot of people consider this the ‘itch cytokine,’” Rosmarin said about IL-31. “I think that’s an oversimplification—there are roles in inflammation—but it definitely can be quite potent for itch.”

Indeed, data suggest benefit beyond itch relief. Recent phase 2B data assessing 3 different doses of nemolizumab plus topical corticosteroids (TCS) versus placebo in patients with prurigo nodularis showed 30 mg dose of the investigative drug was associated significant improvement in patient EASI scores at 24 weeks.

The data additionally showed the 30 mg treatment arm reported a 67.3% mean change in PP-NRS score from baseline at week 24, compared to just 35.8% in the placebo arm (P <.001).

“In my mind, maybe this is a little bit like difelikefalin or tradipitant where it will do really well in that population that has a really high itch burden, but maybe not a low IGA burden,” Rosmarin said. “Again, this would be a welcome addition to our arsenal.”

Rocatinlimab

A phase 2B trial assessing 4 different doses of the OX40 inhibitor versus placebo in adult patients with moderate to severe atopic dermatitis showed significant percent EASI reductions for each arm at 16 weeks—anywhere from -48.1% to -61.1% among patients in each regimen, versus just -15.0% in placebo patients.

“And this is targeting memory T cells, so we have the possibility of maybe longer-term remissions with this drug—maybe some drug holidays,” Rosmarin said.

Though the safety outcomes with such mechanism of action may be alarming, Rosmarin suggested the clinical data may show “redundancies” with rocatinlimab’s impact on the immune system that doesn’t lead to significant infection risks.

LEO138559

Interestingly, the investigative IL-22 receptor agonist may also inhibit IL-20 and IL-24—a concept that has Rosmarin very excited to learn more about in advanced-stage trials.

In the currently available phase 2A data, 58 adult patients were randomized 1:1 to either 450 mg LEO138559 every 2 weeks or placebo. At 16 weeks, investigators observed that 41.6%, 30.8% and 20.9% of treated patients achieved EASI 75, EASI 90 and even EASI 100, respectively. Comparatively, only 13.7%, 3.5%, and 0% of patients on placebo achieved those marks, respectively.

Another 27.3% of overall treated patients achieved validated IGA for atopic dermatitis, versus 7.0% of placebo patient.

Rosmarin noted the easy comparison that could be made to fezakinumab, an IL-22 inhibitor that generally did not provide significant benefit to patients with atopic dermatitis. The key difference, he explained, may be that fezakinumab targets the IL-22 cytokines, while LEO138559 directly targets the receptor.

“When you block the receptor, you’re also blocking IL-20 and IL-24; those are not as well characterized as we would like right now, but they seem to play role in atopic dermatitis, and maybe that’s even a future target,” Rosmarin said. “So, I’m very optimistic about this medicine and the safety profile from the phase 2 trial looked quite good.”

References

1. ^{Rosmarin D. Emerging AD Therapies Beyond 2023. Presentation at: Revolutionizing Atopic Dermatitis 2023 Spring Conference; April 29 – May 1, 2023; Washington, DC. May 1, 2023.}