IL-23 inhibitor QX004N shows safety, efficacy in plaque psoriasis

Key takeaways:

• 100% of patients treated with 150 mg, 300 mg and 600 mg of QX004N achieved PASI 75 at week 12 and PASI 90 at week 16.
• 87.5% of QX004N-treated patients reported treatment-emergent adverse events.

QX004N, an interleukin-23 inhibitor, showed safety and efficacy in the treatment of moderate to severe plaque psoriasis, according to a study.

“In recent decades, multiple new biologic agents targeting the core inflammatory pathways of the disease have been developed,” Xiaojiao Li, PhD, of the phase 1 clinical trial center at the First Hospital of Jilin University in Changchun, China, and colleagues wrote. “Evidence increasingly supports the pivotal role of the IL-23/helper T cell 17 pathway in the pathogenesis of psoriasis ... establishing IL-23 inhibitors as effective management options for psoriasis.”

QX004N (Qyuns Therapeutics Co. Ltd.) is one such option, according to Li and colleagues.

Administered via subcutaneous injection, QX004N is a humanized immunoglobulin G1 gamma monoclonal antibody that targets IL-23 and has shown results comparable to risankizumab (Skyrizi, AbbVie), an IL-23a inhibitor indicated for multiple inflammatory conditions including plaque psoriasis and psoriatic arthritis.

In a phase 1 clinical trial, Li and colleagues investigated the safety and efficacy of QX004N for the treatment of moderate to severe plaque psoriasis.

The trial was split into two parts. The first was a phase 1a trial that evaluated the drug in healthy participants, whereas the second was a phase 1b trial that investigated the drug’s efficacy in patients with plaque psoriasis.

Phase 1a results

The phase 1a study was a double-blind, randomized, placebo-controlled, single-ascending-dose trial of 55 healthy participants who were assigned to one of five single-injection QX004N treatment groups (10 mg, n = 4; 50 mg, n = 8; 100 mg, n = 8; 300 mg, n = 16; 600 mg, n = 8) or a placebo group (n = 11).

Safety results in this part of the trial showed that 81.8% (n = 36) of QX004N-treated patients and 63.6% (n = 7) of placebo-treated patients reported treatment-emergent adverse events. Most of these adverse events were reported as being drug related in both the QX004N (63.6%; n = 28) and placebo (54.5%; n = 6) groups.

In the QX004N group, 50% of participants treated with 10 mg, 50 mg and 300 mg reported adverse events, whereas 75% and 100% of participants in the 100 mg and 600 mg groups, respectively, reported the same.

The most commonly reported drug-related treatment-emergent adverse events, defined as occurring in more than 10% of participants, in the treatment vs. placebo groups were hypertriglyceridemia, hyperuricemia, hematuria, increased blood uric acid and decreased neutrophil count. According to the study, the events were not contingent on the dose.

While most adverse events were considered grade 1 or 2, there was one grade 3 event (hypertriglyceridemia), as well as one serious adverse event (biochemical pregnancy/abortion). Both the grade 3 and serious adverse event were deemed possibly unrelated to the study drug. No deaths were reported.

Phase 1b results

The second part of the study was a 24-week, double-blind, randomized, placebo-controlled, multiple dose-escalation trial of 30 patients with moderate to severe plaque psoriasis. Eight patients were assigned to each QX004N treatment group — 150 mg, 300 mg and 600 mg — and six received placebo, all given as single injections at weeks 0, 2 and 4. One patient in the placebo cohort withdrew due to lack of efficacy.

Results showed that 100% of patients treated with 150 mg, 300 mg and 600 mg of QX004N achieved PASI 75 at week 12 and PASI 90 at week 16 compared with 33.3% (n = 2) in the placebo group.

Additionally, all patients in the 150 mg, 300 mg and 600 mg QX004N groups reached an IGA score of 0 or 1, whereas the highest proportion of those in the placebo group achieving the same was 66.7% (n = 4).

Overall, 87.5% (n = 21) of QX004-treated patients reported treatment-emergent adverse events vs. 66.7% (n = 4) in the placebo group.

“These results support the continued development of QX004N as a potential treatment option for patients with moderate to severe plaque psoriasis, demonstrating its potential to substantially improve patient outcomes,” the authors concluded.