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 RA B-Cell DepletionAbstract 463 (Poster): TRU-015, a Small Modular ImmunoPharmaceutical (SMIPTM) Drug Candidate Directed Against CD20, Demonstrates Clinical Improvement in Subjects with Rheumatoid ArthritisAUTHORS: DJ Burge, C Shu, RW Martin, TW Littlejohn, DJ Wallace, J Taborn, WR Palmer, A Kivitz. METHODS: TRU-015 is a CD20-directed SMIP (single chain polypeptide) drug candidate that effectively depletes B lymphocytes in a dose-dependent manner. The present study was designed to assess safety and pharmacokinetics of TRU-015 and evaluate clinical responses in RA. Thirty-six RA subjects with active disease despite background MTX were enrolled in this randomized, double-blind, multi-center, placebo-controlled study. Subjects were enrolled into one of three cohorts in a 10:2 (active:placebo) ratio to receive TRU-015 as a single intravenous infusion of 5 mg/kg, two infusions of 2.5 mg/kg, or two infusions of 7.5 mg/kg. Subjects in cohorts with two infusions received the infusions one week apart. Subjects were pre-medicated with peri-infusional steroids. RESULTS: 24 week data was presented at the meeting. ACR 20 responses were observed in 72% of all evaluable subjects and 82% of RF+ subjects. ACR 50 responses were seen in approximately 30% and ACR70 responses in approximately 15% of subjects with higher responses also seen in RF positives. B cells were rapidly depleted and remained depressed through 168 days which was the last time reported. Two patients in the active treatment groups experienced moderate reactions with skin rash in one and flushing in another. No infectious or non-infectious serious AEs related to TRU-015 have been reported, and other AEs were similar in active versus placebo. EDITORIAL COMMENT: Placebo responses were not presented thus raising questions as to the significance of the very high ACR responses. This compound also effectively depleted B cells for prolonged periods with associated clinical efficacy. Though infusion reactions were not common, all patients received periinfusional steroids that may have masked the effect. As in other studies of agents targeting B cells, patients who are RF positive may represent a group that is more likely to respond to this strategy.
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