CCX 354-C at the EULAR 2012

CCX 354-C is an oral CCR1-specific antagonist, which doesn´t have anything to do with Credence Clearwater Rivival. CCR-1, the C-C chemokine receptor 1 is expressed on macrophages, which produce pro-inflammatory cytokines like TNFα, IL-1, and IL-6. I was looking at the EULAR 2012 in Berlin for the results of the study: “Study to Evaluate Safety and Efficacy of CCX 354-C in Subjects With Rheumatoid Arthritis (CARAT-1)”, but for a long time I couldn’t find anything, also there hasn’t been anything in the ACR 2011 Abstracts book. As I found out, the study had been presented as late breaking poster L11 at the ACR and so it isn’t in the book.


Now P.P. Tak and colleagues presented a phase 2 study on CCX 354-C at the EULAR 2012 in Berlin, which sums up the data I was looking for. Primary objective has been the evaluation of safety and tolerability of CCX354-C in patients with rheumatoid arthritis. Secondary objective has been the evaluation of efficacy; the study assessed rheumatoid arthritis disease response measurements: “ACR, DAS28, CRP, and ESR, as well as bone turnover markers”. Results showed an ACR20 in 62% of the 200 mg QD group, which was only 27% in the placebo group at p=0.002. CCX354-C at 200 mg QD was well tolerated and showed clinical efficacy.


[OP0203] ORALLY-ADMINISTERED CCR1 ANTAGONIST CCX354-C IN A PHASE 2 RHEUMATOID ARTHRITIS STUDY
P.P. Tak1, A. Balanescu2, V. Tseluyko3, S. Bojin4, E. Drescher5, D. Dairaghi6, S. Miao6, V. Marchesin6, J. Jaen6, T.J. Schall6, P. Bekker6, and the CARAT-2 Study Group. 1AMC/University of Amsterdam, Amsterdam, Netherlands; 2University of Medicine and Pharmacy, Bucharest, Romania; 3City Clinical Hospital, Kharkiv, Ukraine; 4Spitalul Judetean de Urgenta "Dr. Fogolyan Kristof", Sf. Gheorghe, Romania; 5Veszprém Megyei Csolnoky Ferenc Kórház Nonprofit Zrt., Veszprém, Hungary; 6Chemocentryx, Inc., Mountain View, United States
Conclusions: The novel oral CCR1-specific antagonist CCX354-C at 200 mg QD showed clinical and biologic activity, and appears safe and well tolerated in this study. This is the first demonstration of clinical efficacy in RA with a CCR1 inhibitor, consistent with previous in vitro studies and a synovial biopsy study in humans on the effects of CCR1 blockade.


But let’s have a late brake here. The study may not be in the book, but here is the abstract of the poster presented at the ACR 2011 as “late breaking” in Chicago: https://acr.confex.com/acr/2011/webprogram/Paper24548.html.


Safety and Efficacy of Oral Chemokine Receptor 1 Antagonist CCX354-C in a Phase 2 Rheumatoid Arthritis Study
Paul P. Tak1, Andra Balanescu2, Vira Tseluyko3, Silvia Bojin4, Edit Drescher5, Dan Dairaghi6, Shichang Miao6, Vittorio Marchesin7, Juan Jaen6, Pirow Bekker8 and Thomas J. Schall6, 1EULAR & FOCIS Center of Excellence, AMC/University of Amsterdam, Amsterdam, Netherlands, 2University of Medicine and Pharmacy, Bucharest, Romania, 3City Clinical Hospital, Kharkiv, Ukraine, 4Spitalul Judetean de Urgenta “Dr. Fogolyan Kristof”, Sf. Gheorghe, Romania, 5Veszprém Megyei Csolnoky Ferenc Kórház Nonprofit Zrt., Veszprém, Hungary, 6ChemoCentryx, Inc., Mountain View, CA, 7ChemoCentryx, Mountain View, CA, 8Chemocentryx, Inc., Mountain View, CA
Conclusion: The novel oral CCR1-specific antagonist CCX354-C at 200 mg QD showed clinical and biologic activity, and appears safe and well tolerated in this study. This is the first demonstration of clinical efficacy in RA with a CCR1 blocker, consistent with previous studies in in vitro models of RA and a synovial biopsy study in humans on the effects of CCR1 blockade.


Let’s face it: it’s the same study, it’s the same text, it’s the same …, but I’m still very interested to look into further results during the next meetings. Maybe half a year is not enough. And maybe some people have another definition of “first” than my humble self.