VRTX: Oral Selective JAK3 Inhibitor VX-509 Showed Statistically Significant Improvements in Signs and Symptoms of Rheumatoid Arthritis After 12 Weeks of Treatment in Phase 2b Study
-All doses of VX-509 showed statistically significant ACR20 and ACR50 responses compared to placebo and statistically significant improvement from baseline in DAS28 compared to placebo-
-Three highest doses of VX-509: ACR20 of 58% to 68% versus 18% for placebo; statistically significant ACR70 responses versus placebo-
-Results to be presented at American College of Rheumatology (ACR) Annual Meeting; late-breaker abstract published today on ACR website-
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced 12-week results from an ongoing Phase 2b study of VX-509, an investigational oral, selective Janus kinase 3 (JAK3) inhibitor, dosed once or twice daily in people with active rheumatoid arthritis (RA) taking methotrexate. The study met its primary endpoints of both the proportion of people who achieved at least a 20 percent improvement in signs and symptoms of RA, as measured by the ACR improvement criteria (ACR20), and the change from baseline in Disease Activity Score for 28 joints (DAS28). All doses of VX-509 showed statistically significant ACR20 and ACR50 responses versus placebo and statistically significant improvement from baseline in DAS28 versus placebo. The three highest dose groups showed ACR20 responses of between 58 percent and 68 percent, compared to 18 percent for placebo, and statistically significant ACR70 responses versus placebo.
In the study, the discontinuation rate due to adverse events was 6.6 percent for the pooled VX-509 treatment group and 8.5 percent for the placebo group. Overall, adverse event rates were 51.2 percent in the pooled VX-509 treatment groups compared to 38.0 percent for those who received placebo, and the majority of adverse events observed in the study were mild to moderate.
The results were published online today as part of a late-breaker abstract accepted for an oral presentation at the American College of Rheumatology (ACR) annual meeting. The study is ongoing, and Vertex expects 24-week data to be available in early 2014.
“These results are encouraging and provide further support for the development of VX-509 as a new approach to treating RA and potentially other immune-mediated and inflammatory diseases by selectively targeting JAK3,” said Robert Kauffman, M.D. Ph.D., Senior Vice President and Chief Medical Officer at Vertex. “In this study, treatment with VX-509 showed good tolerability and resulted in significant improvements in the signs and symptoms of RA across all doses tested. We look forward to the presentation of these data at the ACR annual meeting later this month.”
About the Phase 2b Study
This double-blind, randomized, placebo-controlled 24-week Phase 2b study of VX-509 enrolled and dosed 358 people with RA who had active disease despite methotrexate treatment. Patients continued to receive stable doses of methotrexate during the study. Up to 20 percent of people in the study could have previously been treated with a single tumor necrosis factor (TNF) inhibitor. People in the study were randomized to receive placebo or one of four doses of VX-509 (100 mg once daily (QD), 150 mg once daily, 200 mg once daily or 100 mg given twice daily (BID)) for 24 weeks. The data announced today reflect an analysis of the primary endpoints completed after 12 weeks of treatment, which was the pre-specified primary endpoint of the study.
Efficacy Data
The primary endpoints of the study were the proportion of people who achieved an ACR20 response at week 12 and the change from baseline in DAS28 at week 12. Additional secondary endpoints were used to evaluate the clinical activity of VX-509, including ACR50 and ACR70 responses at week 12. In all VX-509 treatment groups, the proportion of people achieving ACR20 and ACR50 and the decrease from baseline in DAS28 were significantly greater than in placebo. The three highest dose groups showed ACR20 responses of between 58 percent and 68 percent, compared to 18 percent for placebo, and statistically significant ACR70 responses versus placebo. Efficacy results are provided below:
In the study, adverse events led to discontinuation in 6.6 percent and 8.5 percent of people in the VX-509 and placebo groups, respectively. Through 12 weeks, adverse event rates were 51.2 percent for the pooled VX-509 treatment group compared to 38.0 percent for those who received placebo, and the majority of adverse events observed in the study were mild to moderate. The most common adverse events in the pooled VX-509 treatment group were headache (8.0 percent), hypercholesterolemia (3.8 percent) and nasopharyngitis (3.5 percent). The safety profile of VX-509 was comparable across all treatment groups. Serious adverse events occurred in equal proportions of people across the pooled VX-509 and placebo treatment groups (5.6 percent). Infections occurred in 22.0 percent of people in the pooled VX-509 treatment group compared to 15.5 percent in the placebo group, and serious infections occurred in 2.8 percent of people in the VX-509 group compared to 1.4 percent for placebo. One death, deemed unrelated to study drug, occurred in the VX-509 100 mg BID group and was due to cardiac failure. Elevations in transaminase levels and decreases in median neutrophil and lymphocyte counts were observed in the VX-509 groups and were generally mild.
Presentation at ACR Annual Meeting
These results were accepted for presentation at the ACR annual meeting, being held October 25-30 in San Diego, CA. The presentation of the results will take place in the “ACR Late-Breaking Abstract Oral Session” on October 29 from 2:30 – 4:00 p.m. PT. The abstract presentation number is “L3.”
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