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Dual JAK-ROCK Inhibitor Shows Promise for Active RA

June 27, 2025
in Health News
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TOPLINE:

Patients with rheumatoid arthritis (RA) tolerated a novel Janus kinase/Roh-associated protein kinase (JAK-ROCK) inhibitor without typical side effects.

METHODOLOGY:

  • Phase 2 clinical trial at nine hospitals and clinics in Poland and Ukraine to assess efficacy of CPL’116, a novel JAK-ROCK inhibitor, for RA.
  • Overall, 106 adults (mean age, 54.4 years; 75% women) with RA were randomly assigned to receive oral CPL’116 at 60 mg (n = 27), 120 mg (n = 25), or 240 mg (n = 26) or placebo (n = 28) twice daily for 12 weeks.
  • Primary endpoint analysis focused on the change from baseline in Disease Activity Score based on 28 joints and C-reactive protein (DAS28-CRP) at week 12.

TAKEAWAY:

  • A 240-mg dose of CPL’116 significantly reduced DAS28-CRP at week 12 (least-squares mean difference, -0.89; P = .010), but reductions with lower doses did not reach statistical significance.
  • In week 2, a case of nonfatal non-ST-elevation myocardial infarction in the 60-mg dose group was possibly related to CPL’116 but a case of bladder cancer in the 240-mg dose group was not.
  • Total cholesterol, low- and high-density lipoprotein cholesterol, triglyceride, or creatine kinase levels were not significantly elevated in any CPL’116 groups compared with the placebo group.

IN PRACTICE:

“The novel mode of action is intriguing, and the concept that targeting ROCK alongside JAK might offset the lipid effects seen with isolated JAK inhibition is of interest; indeed, the study reported an absence of significant changes in lipid parameters or creatine kinase,” experts wrote in an accompanying editorial.

SOURCE:

The study was led by Maciej Wieczorek, PhD, Research and Development Centre, Celon Pharma in Kazuń Nowy, Poland. It was published online on June 11, 2025, in Lancet Rheumatology.

LIMITATIONS:

The trial was conducted exclusively in Poland and Ukraine, and all participants were White individuals, potentially limiting the applicability of results to other regions and ethnic backgrounds. The ongoing military conflict in Ukraine may have caused limited access to advanced medical treatments in these regions. Additionally, the study focused only on patients with inadequate response to methotrexate, which narrows generalizability. 

DISCLOSURES:

This study was funded by Celon Pharma and the National Centre for Research and Development (Poland). One author disclosed being the founder, chief executive officer, and majority owner of Celon Pharma, and held stocks in the company. Five authors reported being employees or former employees of Celon Pharma during the trial and receiving salaries. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.



Source link : https://www.medscape.com/viewarticle/dual-jak-rock-inhibitor-shows-promise-active-ra-2025a1000h9y?src=rss

Author :

Publish date : 2025-06-27 11:04:00

Copyright for syndicated content belongs to the linked Source.

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