WCD News: Janssen's Oral IL-23 Blocker Shows Promise in Phase 2b PsO Study

JNJ-2113 is a novel oral IL-23R antagonist peptide that binds with high affinity to the IL-23R and has properties that allow it to be absorbed with oral dosing.

Janssen’s novel oral interleukin-23 receptor (IL-23R) antagonist peptide JNJ-2113 performed well in the Phase 2b FRONTIER 1 clinical trial of adults with moderate-to-severe plaque psoriasis (PsO), the Company reports.

JNJ-2113 is a novel oral IL-23R antagonist peptide that binds with high affinity to the IL-23R and has properties that allow it to be absorbed with oral dosing. The IL-23/IL-23R signaling pathway plays a critical role in the pathogenesis of immune-mediated inflammatory diseases, including PsO, and JNJ-2113 selectively and potently blocks IL-23 signaling and downstream inflammatory cytokine production. 

A greater proportion of patients who received JNJ-2113 achieved Psoriasis Area and Severity Index (PASI) 75 (primary endpoint) as well as PASI 90 and PASI 100, compared to placebo, at week 16, according to the study which was presented at the 25th World Congress of Dermatology in Singapore.

Now, Janssen plans to advance JNJ-2113 into Phase 3 development for moderate-to-severe plaque PsO and initiate a Phase 2b clinical trial for adults living with ulcerative colitis. 

“This is a really exciting new molecule for the treatment of psoriasis,” Laura Korb Ferris, MD, PhD, tells DermWire. “It is getting a biologic level in activity in an oral medication,” says Dr. Ferris, a professor of dermatology and Director of the University of Pittsburgh Department of Dermatology Clinical Trials Unit at the University of Pittsburgh.

Here’s a breakdown of the Phase 2b FRONTIER 1 results:

PASI 75 Results – Primary Endpoint

The proportions of adult patients receiving JNJ-2113 (n=255)7 who achieved PASI 75 demonstrated the following dose responses at week 16 compared to 9.3% of patients receiving placebo (n=43) (nominal p ≤0.002 for all comparisons):

• 37.2 % at 25 mg daily (n=43)

• 51.2% at 25 mg twice daily (n=41)

• 58.1% at 50 mg daily (n=43)

• 65.1% at 100 mg daily (n=43)

• 78.6% at 100 mg twice daily (n=42)

PASI 90 Results – Secondary Endpoint

The proportions of adult patients receiving JNJ-2113 who achieved PASI 90 demonstrated the following dose responses at week 16 compared to 2.3% of patients receiving placebo (n=43) (nominal p ≤0.002 for all comparisons):

• 25.6% at 25 mg daily (n=43) 
• 26.8% at 25 mg twice daily (n=41) 
• 51.2% at 50 mg daily (n=43) 
• 46.5%at 100 mg daily (n=43) 
• 59.5% at 100 mg twice daily (n=42) 

PASI 100 Results – Secondary Endpoint 

The proportions of adult patients receiving JNJ-2113 who achieved PASI 100 also demonstrated the following dose responses at week 16 compared to 0 percent of patients receiving placebo (n=43) (nominal p ≤0.05 for all comparisons):

• 11.6% at 25 mg daily (n=43) 
• 9.8% at 25 mg twice daily (n=41) 
• 25.6% at 50 mg daily (n=43) 
• 23.3% at 100 mg daily (n=43) 
• 40.5% at 100 mg twice daily (n=42) 

Treatment was generally well tolerated, and the proportions of patients with adverse events were comparable between patient groups. The proportion of participants experiencing one or more adverse events (AEs) was 52.4% (n=111) in the combined JNJ-2113 group and 51.2% (n=52) in the placebo group. Although there was variability across the treatment groups, there was no evidence of a dose-dependent increase in the occurrence of specific AEs across the JNJ-2113 treatment groups.1 The most frequent system organ class involved in AEs in all groups was infections and infestations, which were 30.2% (n=64) vs. 27.9% (n=12) in the combined JNJ-2113 group vs. placebo group, respectively; of these, the most common were comparable between groups: COVID-19 (10.8% [n=23] vs. 11.6% [n=5]), nasopharyngitis (7.1% [n=15] vs. 4.7% [n=2]), and upper respiratory tract infection (2.4% [n=5] vs. 2.3%  [n=1]).