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Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

Objective: Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor in development for treatment of several immunological diseases. Efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks.

Methods: This placebo-controlled, dose-ranging, phase IIb study randomized participants to brepocitinib 10 mg once daily (QD), 30 mg QD, 60 mg QD, or placebo, advancing to brepocitinib 30 or 60 mg QD at week 16. The primary endpoint was American College of Rheumatology (ACR)20 response rate at week 16. Secondary endpoints included response rates of ACR50/70, 75% and 90% improvement in Psoriasis Area and Severity Index (PASI75/90), and Minimal Disease Activity (MDA) at weeks 16 and 52. Adverse events (AEs) were monitored throughout.

Results: Overall, 218 participants were randomized and treated. At week 16, brepocitinib 30 and 60 mg QD groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus placebo (43.3%) and significantly higher ACR50/70, PASI75/90, and MDA response rates. Response rates were maintained or improved through week 52. AEs were mostly mild/moderate; serious AEs (15) in 12 (5.5%) participants included infections in 6 (2.8%) in brepocitinib 30 and 60 mg QD groups. No major adverse cardiovascular events or deaths occurred.

Conclusion: Brepocitinib 30 and 60 mg QD were superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study with a safety profile consistent with other brepocitinib clinical trials.

 

Comments:

The study described is a phase IIb clinical trial that evaluated the efficacy and safety of brepocitinib, a tyrosine kinase 2/Janus kinase 1 inhibitor, in the treatment of psoriatic arthritis (PsA). PsA is an immunological disease characterized by inflammation of the joints and skin.

The study employed a placebo-controlled, dose-ranging design and enrolled participants with moderately-to-severely active PsA. The participants were randomly assigned to receive brepocitinib at different doses (10 mg once daily [QD], 30 mg QD, or 60 mg QD) or placebo. At week 16, participants initially receiving placebo were switched to brepocitinib 30 or 60 mg QD.

The primary endpoint of the study was the American College of Rheumatology (ACR)20 response rate at week 16. ACR20 refers to a 20% improvement in certain measures of arthritis signs and symptoms. Secondary endpoints included ACR50/70 response rates (50%/70% improvement), 75% and 90% improvement in the Psoriasis Area and Severity Index (PASI75/90), and Minimal Disease Activity (MDA) at weeks 16 and 52. Adverse events (AEs) were monitored throughout the study.

A total of 218 participants were randomized and treated in the study. At week 16, the groups receiving brepocitinib 30 and 60 mg QD showed significantly higher ACR20 response rates (66.7% and 74.6%, respectively) compared to the placebo group (43.3%). Furthermore, the brepocitinib groups demonstrated significantly higher response rates for ACR50/70, PASI75/90, and MDA. These response rates were sustained or improved through week 52.

In terms of safety, brepocitinib was generally well tolerated over the 52-week study period. Most adverse events reported were mild to moderate in severity. Serious adverse events occurred in 12 participants (5.5%), with a total of 15 events. Infections accounted for six of the serious adverse events, observed in participants receiving brepocitinib 30 and 60 mg QD. Notably, no major adverse cardiovascular events or deaths were reported.

In conclusion, the study demonstrated that brepocitinib at doses of 30 mg and 60 mg QD was superior to placebo in reducing signs and symptoms of PsA. Brepocitinib exhibited a favorable safety profile consistent with previous clinical trials of the drug. These findings support the potential use of brepocitinib as a treatment option for PsA, although further studies are needed for regulatory approval and long-term safety evaluation.

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