Phase III SELECT-EARLY trial of ABT 494 meets endpoint in rheumatoid arthritis.- AbbVie.

AbbVie announced positive top-line results from the phase III SELECT-EARLY trial showing that both doses of ABT 494 (upadacitinib monotherapy) (15 mg and 30 mg) met the primary endpoints of ACR50a at week 12 and clinical remission at week 24 versus methotrexate (MTX) in adult patients with moderate to severe rheumatoid arthritis. Additionally, all ranked secondary endpoints were met.

The ongoing study evaluates upadacitinib, an investigational oral JAK1-selective inhibitor, as a monotherapy treatment compared to methotrexate monotherapy in adults with rheumatoid arthritis who were methotrexate-naïve. A significantly higher proportion of upadacitinib patients in both doses achieved superior responses compared to patients on methotrexate at week 12 and 24. Results at week 12 showed that of patients receiving an oral once-daily dose of upadacitinib 15/30 mg, 52/56 percent achieved ACR50, respectively, compared with 28 percent of patients receiving methotrexate.

At week 24, clinical remission (based on Disease Activity 28 [DAS28] C-Reactive Protein [CRP]) was achieved by 48/50 percent of patients receiving upadacitinib 15/30 mg, respectively, compared to 18 percent of patients receiving methotrexate. At week 12, 76/77 percent of patients receiving 15/30 mg of upadacitinib, achieved ACR20, respectively, compared to 54 percent in the methotrexate group. Additionally, ACR70 was achieved by 32/37 percent of patients receiving 15/30 mg of upadacitinib, respectively, compared to 14 percent receiving methotrexate at week 12. Clinical remission was achieved by 36 percent and 41 percent of patients in the 15 mg and 30 mg groups, respectively, compared to 14 percent of patients receiving methotrexate at week 12. At week 24, 79/60/44 percent of patients receiving the 15 mg dose of upadacitinib and 78/66/50 percent of patients receiving the 30 mg dose of upadacitinib achieved ACR20/50/70 response, compared to 59/33/18 percent of patients receiving methotrexate.

Following 24 weeks of treatment, both doses of upadacitinib monotherapy significantly inhibited radiographic progression as measured by the change in modified total Sharp score (mTSS) from baseline, compared to methotrexate. The inhibition of joint damage is important for rheumatoid arthritis patients as this can lead to permanent loss of function and subsequent disability. In this study, the safety profile of upadacitinib was consistent with previously reported results from the other SELECT trials in rheumatoid arthritis. Further results from SELECT-EARLY will be presented at a future medical meeting and published in a peer-reviewed publication. AbbVie plans global regulatory submissions for upadacitinib in rheumatoid arthritis in the second half of 2018.