Background/Purpose: While interleukin-6 (IL-6) blockade with monoclonal antibodies is an established, clinically validated mechanism for the treatment of rheumatoid arthritis (RA), the need for significant quantities of protein due to the potency and half-life of available agents with resultant high cost has limited patient access to these medications. We have developed gerilimzumab, a highly potent anti-IL6 cytokine antibody with a long half-life, to address this problem. Gerilimzumab is a humanized llama antibody with femtomolar potency and a Fc region mutation engineered to prolong half-life. A 20-24-day half-life in cynomolgus monkeys was observed. We now evaluate the safety of gerilimzumab in healthy volunteers and whether the long half-life seen in monkeys translates to a long half-life in human subjects.

Methods: The primary objective of our multi-ascending dose study was to assess the safety and tolerability of gerilimzumab when administered as three SC doses at 4-weekly intervals to healthy adult participants. Two cohorts were included in the study: a gerilimzumab 5 mg and 20 mg cohort. Each cohort included 6 subjects treated with active drug and 3 subjects treated with placebo.

Results: No SAEs or deaths were observed during the study. All adverse events were mild or moderate in severity. One participant was withdrawn due to a mild urticarial rash. Only injection-site erythema occurred in a dose dependent manner. No laboratory, vital signs or ECG findings of clinical significance were assessed by the investigator. All participants in the placebo and gerilimzumab groups recorded negative ADA test results at all time points. While steady state was not achieved in this study, the estimated half-life of gerilimzumab was approximately 50 days for the 20 mg cohort and exposure was dose-proportional. No anti-drug antibodies were detected over the course of the study. A numeric decrease from baseline in C-reactive protein, a pharmacodynamic marker of an anti-IL6 effect, was observed in the gerilimzumab groups.

Conclusion: Overall, gerilimzumab (within the dose range 5 mg to 20 mg) appeared safe and well tolerated when administered as three SC injections with an inter-dosing interval of 28 days to healthy volunteers. Gerilimzumab’s long half-life and expected potency (based upon preclinical data) differentiate it from other anti-IL6 monoclonal antibodies and provides the potential for a very low cost and conveniently dosed biologic therapy for RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-development-of-a-new-anti-interleukin-6-blocker-for-rheumatoid-arthritis-patients/