CFZ533, Novel Anti-CD40 Monoclonal Antibody at the ACR 2016 Annual Meeting in Washington

CFZ533 (or OM11-62-MF) is a a novel anti-CD40 MAB. CFZ533 is fully human, non-agonistic Fc-silent, and has been developed for the treatment of autoimmune diseases and the prevention of organ transplant rejection. This MAB is different to BI 655064, which is an antagonistic anti-CD40 MAB.

Alan Slade an colleagues presented [1582]: “Assessment of Safety, Pharmacokinetics and Pharmacodynamics of a Novel AntiCD40 Monoclonal Antibody, CFZ533, in Healthy  Volunteers and in Rheumatoid Arthritis Patients”. “The objective of present study was to assess the safety, pharmacokinetics (PK) and pharmacodynamics activity (PD) of CFZ533 in humans”. The double-blinded, placebo controlled study tested 48 healthy volunteers and 12 rheumatoid arthritis patients. Conclusion: “The favorable safety and tolerability profile of CFZ533 coupled with a predictable concentration-CD40 receptor occupancy relationship and suppression of a primary T cell-dependent antibody response supports future clinical trials of CFZ533 in select autoimmune diseases and transplantation”.

The idea behind CFZ533 in rheumatoid arthritis is blocking the CD40-CD154 pathway to prevent T cell-dependent antibody responses. Studies on BI 655064 showed moderate efficacy in rheumatoid arthritis patients and a reduction of circulating inflammatory and bone resorption biomarkers, but this has yet to be shown in CFZ533. Both MABs address CD-40, but both are different. It isn’t clear yet, if the companies involved invest in further development of the two MABs. And it will take years to do the necessary studies.

Reference:

Slade A, Koo P, He Y, Espie P, Auger-Sarrazin A, Rush JS, Gergely P. Assessment of Safety, Pharmacokinetics and Pharmacodynamics of a Novel Anti-CD40 Monoclonal Antibody, CFZ533, in Healthy Volunteers and in Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/assessment-of-safety-pharmacokinetics-and-pharmacodynamics-of-a-novel-anti-cd40-monoclonal-antibody-cfz533-in-healthy-volunteers-and-in-rheumatoid-arthritis-patients/. Accessed December 2, 2016.

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BI 655064, an Antagonistic Anti-CD40 Antibody, in the Treatment of Rheumatoid Arthritis at the 2016 Annual Meetings of EULAR and ACR

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 [1588]: “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.

Links:

http://rheumatologe.blogspot.de/2012/08/targeting-cd-40-preliminaries-at-eular.html

http://adisinsight.springer.com/drugs/800035513

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 [1588]: “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

AbbVie and Boehringer Ingelheim announce global collaboration on promising immunology compounds  https://www.boehringer-ingelheim.com/press-release/abbvie-boehringer-ingelheim-immunology-compounds

 

 

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