At the 2025 ODAC Dermatology Conference, expert dermatologist Anthony Fernandez, MD, PhD presented a masterful talk on Advances in Psoriasis Treatment: Emerging Therapies and Future Directions. He explored emerging therapies and future directions in psoriasis management. Since 2004, the FDA has approved 14 novel systemic agents to treat moderate to severe psoriasis, 12 of which are biologics, and two are small molecule inhibitors. Despite the effectiveness of current treatments, promising research suggests the potential development of even better medications in the future.
Oral Small Molecule Cytokine Inhibitors
There are currently several oral cytokine inhibitors in development for treatment of psoriasis. IL-17 inhibitors, presently named DC806 and DC853, have completed phase 1C studies and results of the DC806 phase 1C study were released in 2022. The results showed significant efficacy compared to placebo, with a mean reduction of almost 44% in PASI score after four weeks in the high-dose group (800mg twice daily), versus a 13% reduction in the placebo group. As ownership of the above medications transitioned from Dice Therapeutics to being acquired by Eli Lilly, phase 2 study results for DC806 in psoriasis have not yet been released. The focus seems to have moved to DC853, which appears to be a more potent and stable IL-17 inhibitor than DC806. A multicenter phase 2 trial assessing efficacy and safety of DC853 in psoriasis patients is currently actively enrolling participants.
There has been more data shared about Johnson and Johnson’s oral IL-23 receptor antagonist, icotrokinra. Results of a phase 2 clinical trial were published in the New England Journal of Medicine in 2024. All dosing groups showed significant efficacy compared to placebo in meeting the trial’s primary endpoint (PASI 75 at week 16), with an acceptable adverse effect profile. Based on the phase 2 results, multiple phase 3 trials were designed. Two of these phase 3 trials, ICONIC-LEAD and ICONIC-TOTAL, have been completed and results support that icotrokinra was superior to placebo in meeting the co-primary endpoints (PASI 90 and IGA 0/1 responses at week 16). Two other phase 3 trials (ICONIC-ADVANCE 1 and 2), in which icotrokinra’s efficacy and safety is being compared to those of both placebo and deucravacitinib. Based on the results of ICONIC LEAD and ICONIC TOTAL, Dr. Fernandez expects the data to be submitted to the FDA in the near future, and a likelihood that icotrokinra will eventually be granted FDA approval for treating psoriasis.
Nanobodies
Nanobodies are fragments of monoclonal antibodies, specifically the variable domains that bind antigen. Advantages of nanobodies over monoclonal antibodies include greater stability and deeper penetration into diseased tissue due to their smaller size, potentially leading to more complete cytokine inhibition and better efficacy than traditional monoclonal antibodies. The most studied nanobody in dermatology is sonelokimab. It is composed of three domains: one domain inhibits interleukin 17F, one binds albumin, and the third potently inhibits either interleukin 17A or interleukin 17F. This nanobody is administered via subcutaneous injection every four weeks. Results of a phase 2B study looking at efficacy and safety of sonelokimab for treating psoriasis were published in The Lancet in 2021. Participants were randomized into different dosing groups of sonelokimab, as well as secukinumab and placebo. All dosing groups of sonelokimab had significantly better efficacy than placebo. At week 12, 76% of patients in the sonelokimab 120 mg augmented load group achieved a PASI 90 response, and a third achieved a PASI 100 response. Results were even better at week 24. Currently, there are no phase 3 trials occurring specifically for psoriasis. However, two phase 3 trials exploring the efficacy and safety of sonelokimab for treating psoriatic arthritis are actively recruiting patients. Additionally, there are two phase 3 trials looking at the safety and efficacy of sonelokimab for hidradenitis suppurativa also actively recruiting patients.
Strategies to Administer Interleukin-23 Inhibitors
The key pathogenic cell in psoriasis is the skin-resident memory Th17 cell, which requires interleukin-23 for maturation and survival. Based on this knowledge, Dr. Andy Blauvelt, a dermatologist who is well-known for his research in psoriatic disease, developed a hypothesis that aggressive treatment with interleukin-23 inhibitors may be able to eliminate these pathogenic Th17 cells, inducing long-term remissions or even cures. This is a strategy that has been termed, “knockout therapy”.
Dr. Blauvelt designed and carried out a phase 2 study (The “KNOCKOUT” study) to test this hypothesis. Patients with severe psoriasis (at least 10% body surface area involvement) were enrolled. Patients were aggressively treated with the interleukin-23 inhibitor, Risankizumab, at either 300 mg or 600 mg (double or quadruple the approved dosing, respectively) at week zero, week four, and week 16, and then treatment was stopped. Those patients were then followed over time. Lesional skin biopsies were performed at week zero and week 52 to assess the number of skin-resident memory Th17 cells. Patients were followed to week 100. At week 52, , 61% of patients maintained a PASI 90 response, and 44% still had complete skin clearance (PASI 100) despite not receiving IL-23 inhibitor or other psoriasis treatments since week 16. At week 88, > 25% of patients still maintained a PASI 90 response, and about 17% still had a PASI 100 response. Additionally, there was a significant reduction in skin-resident memory Th17 cells in lesional skin at week 52 compared to week zero. Based on the results of this trial, it is expected future, larger trials may further explore the more aggressive use of IL-23 inhibitors in hopes of inducing longer disease remissions and possibly altering the disease course of psoriasis.
Other Strategies in Development
Dr. Fernandez recommends paying close attention to the ongoing development of CAR T-cell therapy. It is being explored to treat numerous immune-mediated diseases, including lupus erythematosus and dermatomyositis, with early data being very promising. Although clinical trials assessing the efficacy and safety of CAR T-cell therapy for psoriasis have not been done, this technique is being explored as a future psoriasis treatment strategy.
In conclusion, despite the abundance of systemic medicines to treat psoriasis, ongoing research provides hope for even better outcomes for patients with psoriasis in the future.
This information was presented by Dr. Anthony Fernandez during the 2025 ODAC Dermatology Conference. The above session highlights were written and compiled by Dr. Kala Hurst.
