Investigational drug achieves promising results in patients with rheumatoid arthritis who previously had an inadequate response to DMARD therapy.
Monotherapy with tasocitinib, an investigational novel oral Janus Kinase (JAK) inhibitor with blockbuster potential, achieved promising results in patients with rheumatoid arthritis (RA) who previously had an inadequate response to disease-modifying anti-rheumatic drug (DMARD) therapy. Results of the phase III ORAL Solo randomized, placebo-controlled trial showed that tasocitinib monotherapy significantly improved the signs and symptoms of RA as well as physical function compared to placebo after three months of treatment.
“These first results of the first phase III study of tasocitinib monotherapy demonstrate clinically and statistically significant efficacy, and safety was consistent with phase II RA data,” said Roy Fleischmann, University of Texas Southwestern Medical Center, Dallas, TX. Fleischmann presented these results at a late-breaking session during the 2010 Annual Scientific Sessions of the American College of Rheumatology.
ORAL Solo is one of six phase III trials in the large development program for tasocitinib, a drug that takes a novel approach to RA by targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network. According to information disseminated by Pfizer, Inc., the drug’s selective inhibition of JAK pathways blocks cytokine signaling, cytokine-induced gene expression, and activates cells involved in the immune and inflammatory response.
ORAL Solo was a six-month, randomized, double-blind, placebo-controlled study looking at the efficacy and safety of tasocitinib 5 mg or 10 mg twice daily versus placebo in patients with moderate to severe active RA who had a previous inadequate response to either traditional or biologic DMARD therapy. Patients were randomized 2:2:1 to tasocitinib 5 mg or 10 mg b.i.d versus placebo. At month 3, all placebo patients were blindly crossed over to either dose of the novel agent.
At month 3, both doses of tasocitinib were statistically superior to placebo as measured by ACR20 (20% improvement from baseline in the ACR scale) response rates (P<.0001 for both doses vs. placebo). At month 3, improvement on the Health Assessment Questionnaire Disability Index (HAQ-DI) was also statistically significant for both doses of tasocitinib versus placebo (P<.0001). A Disease Activity Score (DAS)-28-4 score of <2.6 was defined as remission, and although remissions were numerically greater in patients treated with the novel agent versus placebo, the difference was not statistically significant.
Response rates as measured by ACR50(50% improvement from baseline) and ACR 70 (70% improvement from baseline) were also significantly superior for both doses of tasocitinib at month 3, he said. P values were not available for the month 6 data, as all patients were on active therapy from months 3 to 6.
A similar frequency of adverse events was seen across all treatment groups. Adverse events were reported in 54.1% of patients over months 0 to 3 and in 40% over months 3 to 6. Serious adverse events were reported in 41% of patients, and serious infections occurred in six patients over six months of the study. Among patients treated with tasocitinib, significant decreases in neutrophil count and increases in LDL and HDL cholesterol were observed compared with placebo during months 0-3. Fleischmann said these changes were consistent with data from the global Phase II RA program. After month 3, these changes remained stable. Few patients in any treatment group had elevated transaminase levels.