OP-0252 –
Repeated Therapy with TRU-015 is Well Tolerated and Results in Consistent Pharmacodynamic Effects in Rheumatoid Arthritis Patients
Burge, Martin, Wallace, Bookbinder, Kirsch, Bass, Shu, Littlejohn III; Seattle, United States
Objectives
TRU-015 is an anti-CD20 molecule in early phase trials that differs from other B cell depleting agents in that its molecular structure is smaller than other monoclonal antibodies in the same class. Smaller structures may lead to a more durable response compared to larger antibody structures. Early (Phase I/II) efficacy and safety were presented.
Methods
RA patients who received a single course of TRU-015 were retreated with a single course of 5 or 15 mg/kg, depending on initial dosing of their first course and followed for safety, pharmacodynamics, and immunogenicity out to 24 weeks. A placebo group was not involved.
Results
Of the 54 patients eligible for retreatment, 38 were retreated. Of these, 36 had analyzable data. Two retreatments were received in 29 of these. The maximum number of courses of TRU-15 received by any patient was six. Women made up 76% of the subjects with a mean age of 54 years. Retreatment was generally well tolerated, with 4 patients reporting an adverse event on the day of retreatment (one each of insomnia, synovial cyst, facial flushing, and pruritis). No serious adverse events, deaths, or withdrawals due to adverse events were reported. Pharmacodynamic profiles for retreatments were similar to those seen with the initial treatment course. ACR responses were available in only 17 subjects and included ACR20, 50, and 70 responses of 50%, 25%, and 15%, respectively, which were, in general, sustained responses from initial treatment.
Conclusions
Repeat administration was associated with similar pharmacodynamics as the first treatment course, without an increase in adverse safety events or immunogenicity.
Editorial Comment
There are several potential new anti-CD20 agents being studied in RA. Presumably the efficacy of the agent would be similar to other anti-CD20 agents, provided that the novel antibody structure of the Fc portion does not interfere with the ability of the antibody to fix complement and/or participate in cell mediated killing. A head to head trial with other anti-CD20 agents would be required to establish an advantage in infusion reactions or durability of response compared to rituximab, a trial which is still in the future for this agent still in the early stages of development.
