I have been interested in CD-40 for a couple of years now. Boehringer Ingelheim has developed a CD40 antigen inhibitor, BI 655064. Boehringer Ingelheim has terminated a phase I trial for immune thrombocytopenic purpura in the US this September. Adisinsight didn’t show any new reports on phase 1 studies in rheumatoid arthritis, which is strange as there had been two abstracts at the EULAR 2016 Annual Meeting in London and one abstract at the ACR 2016 Annual Meeting in Washington, which concluded just a couple of days ago.
S. Visvanathan and collegues presented at the EULAR 2016 [FRI0231]:“Treatment with BI 655064 (antagonistic anti-CD40 antibody) modulates biomarkers associated with Rheumatoid arthritis (RA)”. In conclusions we read: These results demonstrate that treatment of RA patients with BI 655064 decreases activated B cell subsets, inhibits the production of pathogenic autoantibodies, and reduces the level of circulaiting inflammatory and bone resorption biomarkers at 12 wks [weeks].”
S. Daniluk and collegues presented at the EULAR 2016 [SAT0147]: “Safety and efficacy of BI 655064, an antagonistic Anti-CD40 antibody in rheumatoid arthritis (RA) patients”. In conclusions the authors tell us: “In this relatively small proof-of-clinical-concept trial, treatment of
MTX IR RA patients with BI 655064 did not indicate a relevant safety concern and showed moderate efficacy, which might have been impacted by the relatively high placebo response rate and the imbalance in baseline CRP.”
S. Visvanathan and collegues presented at the ACR 2016 : “Treatment with BI 655064 (Antagonistic Anti-CD40 Antibody) Modulates Clinical and Biomarker Parameters Associated with Rheumatoid Arthritis (RA)”.In conclusion we read: “Treatment of MTX-IR RA [methotrexate inadequate responders rheumatoid arthritis] patients with BI 655064 resulted in moderate efficacy, […]. Treatment with BI 655064 decreased selected activated B cell subsets, inhibited RF [rheumatoid factor] production, and reduced levels of select circulating inflammatory and
bone resorption biomarkers through 12 wks [weeks] in RA patients.”
The studies show moderate efficacy in rheumatoid arthritis patients with inadequate response to MTX and a reduction of circulating inflammatory and bone resorption biomarkers, which might be a hint at the possibility to reduce or stop radiographic progression. Half a year ago AbbVie and Boehringer Ingelheim announced sharing responsibility for future clinical development. “AbbVie gains rights to an anti-CD-40 antibody, BI 655064, currently in Phase 1 development. [March 2016]”. Hopefully, a phase 2 study is initiated soon.
S. Visvanathan, M. Ramanujam, C. Schoelch, R. Vinisko,U. Mueller-Ladner, S. Padula, J.S. Fine, J. Steffgen: FRI0231 / TREATMENT WITH BI 655064 (ANTAGONISTIC ANTI-CD40 ANTIBODY) MODULATES BIOMARKERS ASSOCIATED WITH RHEUMATOID ARTHRITIS (RA). DOI: 10.1136/annrheumdis-2016-eular.2051
S. Daniluk, R. Ptaszynski, U. Mueller-Ladner, A. Petrikova, H. Kellner, E. Dokoupilova, B. Kwiatkowska, R. Alten, C. Schwabe, B. Rosenstock, T. Doan11, R. Thiedmann , F. Fleischer, J. Hilbert, S. Visvanathan, S. Padula, J. Steffgen: SAT0147 / SAFETY AND EFFICACY OF BI 655064, AN ANTAGONISTIC ANTI-CD40 ANTIBODY IN RHEUMATOID ARTHRITIS (RA) PATIENTS. DOI: 10.1136/annrheumdis-2016-eular.1271
Sudha Visvanathan, Meera Ramanujam, Corinna Schoelch, Patrick Baum, Richard Vinisko, Ralf Thiedmann, Ulf Müller-Ladner, Stefan Daniluk, Rafal Ptaszyński, Steven Padula, Jay S. Fine and Jürgen Steffgen : “Treatment with BI 655064 (Antagonistic Anti-CD40 Antibody) Modulates Clinical and Biomarker Parameters Associated with Rheumatoid Arthritis (RA)”. http://acrabstracts.org/abstract/treatment-with-bi-655064-antagonistic-anti-cd40-antibody-modulates-clinical-and-biomarker-parameters-associated-with-rheumatoid-arthritis-ra