Trubion Pharmaceuticals, Inc. (Nasdaq: TRBN) today announced Pfizer's decision to discontinue development of TRU-015 (PF-05212374), an investigational drug in Phase 2 evaluation for the treatment of rheumatoid arthritis (RA) developed under the companies' CD20 collaboration. However, Pfizer has confirmed that it will continue to develop SBI-087 (PF-05230895), Trubion's next-generation, humanized, subcutaneous CD20 RA product candidate also in Phase 2 clinical evaluation.
Pfizer's decision is based on preliminary results from the Phase 2b (2203) randomized, parallel, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of two dosing regimens (a single dose of 800mg TRU-015 compared with an induction dose of 800mg TRU-015 followed by an additional dose of 800mg TRU-015 at week 12) in combination with methotrexate in patients with active rheumatoid arthritis.
Although the ACR (American College of Rheumatology) 20/50/70 results in the Phase 2 (2203) study were consistent with previous studies and similar to other B-cell-depleting therapies, the results did not meet the internally predefined primary endpoint, a 20% difference in ACR50 response compared with placebo at week 24 (p value = 0.06 for the single-dose group ACR 50 compared with placebo ands decision to discontinue development.
TRU-015 demonstrated biologic activity including peripheral B-cell depletion and a statistically significant decrease in C-reactive protein in both dose groups compared with placebo. Specifically, ACR 20 was 67.1% for the induction-dose group, 61.3% for the single-dose group and 43.2% for the placebo group. ACR 50 was 27.4% for the induction dose, 29.3% for the single dose and 16.2% for placebo. ACR 70 was 9.6% for the induction dose, 9.3% for the single dose and 2.7% for placebo. TRU-015 was generally well-tolerated, and serious adverse events and medically important infection rates in both dose groups were similar to placebo.
"Given the higher than usual placebo response, TRU-015 did not meet the internal hurdle for continued development," said Scott C. Stromatt, M.D., senior vice president and chief medical officer at Trubion. "It is evident that the drug has significant biological and clinical activity with no significant safety concerns, but market dynamics dictate that we pursue a differentiated and best-in-class product to bring into Phase 3 development. At this time our next-generation CD20 SMIP product candidate, SBI-087, meets that criteria, and its Phase 2 development will continue."
"Although we are not moving forward with this compound, we are encouraged by our analysis to date of SBI-087," said Evan Loh, senior vice president of BioTherapeutics Research and Development at Pfizer. "The goal of our collaboration with Trubion continues to be the development of best-in-class CD20 therapies, and we look forward to the results of the ongoing SBI-087 Phase 2 study."
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