CC-99677: A NOVEL, ORAL, SELECTIVE MK2 INHIBITOR WITH SUSTAINABLE MULTI-CYTOKINE INHIBITION FOR THE TREATMENT OF ANKYLOSING SPONDYLITIS AND OTHER INFLAMMATORY DISEASES
Authors: Kofi Mensah et al.
The p38 Mitogen-activated protein kinases (MAPK) participate in the signaling cascade controlling cellular responses to cytokines. Previous studies with p38 MAPK inhibitors have failed because of tachyphylaxis. The protein kinase MK2 is activated downstream of p38 in the signaling cascade. Activation of MK2 increases expression of cytokines such as IL-17, IL-6 and TNFα. This study reports the results of a Phase 1 trial with the MK2 inhibitor CC-99677 in healthy volunteers. The treatment was safe and well tolerated. In doses between 10 and 150mg/d a sustained reduction of TNFα and other cytokine and chemokine production in blood cells of patients ex vivo was observed.
This study shows promising results with a new kinase inhibitor targeting MK2. In contrast to previous attempts to target p38 who have failed because of a rapid loss of effect, MK2 inhibition showed a sustained effect on the production of various cytokines. A phase 2 study is planned in patients with spondyloarthritis. The development of new kinase inhibitors may offer new therapeutic options for various rheumatic diseases.