The study showed positive results in a difficult-to-treat patient population.
AbbVie has announced positive top-line results from the phase 3 SELECT-BEYOND clinical trial evaluating upadacitinib (ABT-494) to treat patients with moderate to severe rheumatoid arthritis (RA) who did not adequately respond to or were intolerant to treatment with biological disease-modifying anti-rheumatic drugs (DMARDs/bDMARDs).
Rheumatoid arthritis affects an estimated 23.7 million people. Despite treatment progress, many patients do not achieve remission or low disease activity (LDA) targets, AbbVie said in a statement.
“Particularly exciting is the proportion of patients who achieved clinical remission by week 12 and 24, despite having inadequate responses with previous biologic therapies,” said Michael Severino, M.D., executive vice president, research and development and chief scientific order, AbbVie. “Together with previously reported results from SELECT-NEXT, these data further support the potential for upadacitinib to be a meaningful treatment option for rheumatoid arthritis patients.”
In the phase 3 study, the safety profile of upadacitinib was consistent with previously reported phase 2 trials and the phase 3 SELECT-NEXT clinical trial reported in June.
The SELECT program phase 3 RA program evaluated more than 4,000 patients with moderate to severe rheumatoid arthritis in 6 studies, including assessments of efficacy, safety and tolerability across multiple RA patient populations. Key measures evaluated include American College of Rheumatology Criteria (ACR) responses, disease activity and inhibition of radiographic progression.
SELECT-BEYOND is a phase 3, multicenter, randomized, double-blind, placebo-controlled study, evaluating the safety and efficacy of 2 once-daily doses — 15 mg and 30 mg — of upadacitinib in adult patients with moderate to severe arthritis. Patients participating in the study are on a stable dose of conventional synthetic DMARDs (csDMARDs) and have had an inadequate response or intolerance to bDMARDs.
Primary endpoints include the percent of subjects achieving an ACR20 response and LDA after 12 weeks of treatment. Secondary endpoints include the percentage of patients achieving ACR50 and ACR70 response at week 12. ACR is defined as improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.
Results from the SELECT-BEYOND trial showed that after 12 weeks of treatment, both once-daily doses of upadacitinib — 15 mg and 30 mg — met the primary endpoints of ACR20 and LDA. All ranked secondary endpoints were also achieved with both doses. Positive results were displayed in a difficult-to-treat population in which more than half had previously been treated with 2 or more biologics.
Week 12 results showed that of patients receiving an oral once-daily dose of 15 mg or 30 mg, ACR20/50/70 response was achieved in 65/34/12% of patients with the 15-mg dose, and 56/36/23% with the 30-mg dose, compared to 28/12/7% in the placebo group. The results were statistically significant compared to placebo for all comparisons except ACR70 for the 15-mg dose.
A significantly higher proportion of upadacitinib patients in both doses achieved LDA and clinical remission targets at week 12 compared to patients receiving placebo. LDA was achieved by 43% and 42% of patients in the 15 mg and 30 mg groups, compared to 14% of patients receiving placebo. Clinical remission was achieved by 29% and 24% of patients in the 15 mg and 30 mg groups, compared to 10% of patients receiving placebo.
Week 24 results were also encouraging, as patients treated with upadacitinib from study entry, ACR20/50/70 response was achieved in 62/43/22% of patients with the 15-mg dose and 59/43/24% with the 30-mg dose. LDA was achieved by 52% of patients receiving either dose. Clinical remission was achieved by 32% and 35% of patients in the 15-mg and 30-mg groups. Since all placebo patients received either upadacitinib 15 mg or 30 mg beginning at week 12, comparisons to placebo cannot be made.
During the placebo-controlled period, serious adverse effects occurred in 5/7/0% of patients in the 15 mg/30 mg/placebo groups. No new safety signals were detected. There were 2 death reports; 1 was a patient in the 15-mg dose group with cause of death unknown; the second was a patient in the 30-mg dose group who presented with fever and diarrhea, subsequent heart failure and presumed pulmonary embolism (PE) during hospitalization. Inclusive of the mentioned case, a total of 2 cases of PE and no deep vein thrombosis (DVT) were reported during the placebo-controlled period.
Further results of SELECT-BEYOND, the second of 6 studies in the SELECT RA clinical trial will be presented at a future medical meeting and published in a peer-reviewed publication.
Upadacitinib, an investigational oral JAK1-selective inhibitor, plays a role in the pathophysiology of rheumatoid arthritis and other immune-mediated inflammatory disorders. It’s being studied as a once-daily therapy in RA in the SELECT program and across multiple immune-mediated diseases like psoriatic arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis.
A press release was made available.