Oral IL-23 inhibitor improves psoriasis through 1 year

Key takeaways:

• JNJ-77242113 is a targeted oral peptide that inhibits the IL-23 receptor.
• Patients with psoriasis showed improvement with JNJ-77242113, including those who crossed over from placebo.

Patients with moderate to severe psoriasis experienced higher rates of skin clearance through 1 year with oral JNJ-77242113 treatment compared with placebo, according to phase 2 study results.

“Treatment options for plaque psoriasis (PsO) have expanded with the approval of monoclonal antibodies that target inflammatory cytokines or their receptors,” Laura K. Ferris, MD, PhD, clinical vice chair of dermatology at the University of Pittsburgh at the time of the study and the current Clayton E. Wheeler Jr. Distinguished Professor and chair of the department of dermatology at University of North Carolina, Chapel Hill, and colleagues wrote. “While these biologics have demonstrated efficacy and acceptable long-term safety profiles, they are administered via subcutaneous injection, which may not be the preferred mode of administration for all patients.”

The FRONTIER-2 trial is a continuation of the randomized, double-blind, placebo-controlled, dose-ranging, phase 2b FRONTIER-1 trial in which patients who were originally randomly assigned to daily JNJ-77242113 25 mg daily, 25 mg twice daily, 50 mg daily, 100 mg once daily or 100 mg twice daily continued their dosing regimen, and those who were in the placebo group crossed over to JBJ-77242113 100 mg once daily from weeks 16 through 52.

The trial was continued by 89% of the 255 patients in the FRONTIER-1 trial, with 35 patients crossing over from placebo to treatment.

At week 52, PASI 75 was achieved by 49%, 58%, 70%, 65% and 76% of the respective original treatment groups and 66% of those in the crossover group.

At week 16, PASI 90 and PASI 100 was achieved by 60% and 40% of the twice-daily 100 mg group, which the researchers said was “generally maintained” through the end of the study.

IGA 0/1 was achieved by 73.8%, 60.5%, 60.5%, 46.3% and 37.2% of the twice-daily 100 mg, once-daily 100 mg, once-daily 50 mg, twice-daily 25 mg and once-daily 25 mg groups, along with 65.7% of the crossover group at week 52.

Patient-reported outcomes, as measured by least-squares mean (LMM) changes in Psoriasis Signs and Symptoms Diary (PSSD) sign and symptom scores also maintained clinically meaningful improvement between weeks 16 and 52 in all treatment groups, with 75% and 76% of the twice-daily 100 mg group reporting at least a 4-point improvement in itch and pain, respectively.

Adverse events were recorded in 59% of patients from week 16 through week 52, with no dose-dependent increase found. The most common adverse events were nasopharyngitis, upper respiratory tract infection and COVID-19. Serious adverse events occurred in 4% of patients, with all considered not related to the study drug.

“This study demonstrated that patients with moderate to severe PsO can attain sustained, advanced, efficacy and safety using an oral, targeted IL-23-receptor inhibitor,” the authors wrote.