Upadacitinib Meets Primary, Secondary Endpoints for RA Treatment

Global pharmaceutical company AbbVie has announced positive top-line results in the phase III trial of upadacitinib, an investigational oral JAK1-selective inhibitor for the treatment of moderate to severe rheumatoid arthritis (RA).

The current trial tested the drug specifically for RA patients who did not adequately respond to treatment with conventional synthetic DMARDs, according to an AbbVie statement.

“Selective inhibition of the JAK1 pathway may offer a novel treatment for rheumatoid arthritis patients who do not adequately respond to conventional therapies,” said Michael Severino, MD, executive vice president, research and development and chief scientific officer at AbbVie. “We are especially encouraged by the results on the more stringent measures of efficacy, such as ACR70, low disease activity and clinical remission.”

AbbVie’s phase III trial evaluated more than 4,000 patients with moderate to severe RA in six studies, including assessments of efficacy, safety and tolerability across multiple RA patient populations. Results of the phase III trial showed that after a 12 week treatment period, 15mg and 30mg once-daily doses of upadacitinib met the study’s primary endpoints of ACR20 and low disease activity.

The key secondary endpoints of ACR50, ACR70 and clinical remission were also met.

64% of patients receiving a 15 mg oral, once-daily dose of upadacitinib, and 66% of patients receiving a 30 mg dose achieved ACR20, compared to 36% of patients receiving placebo, according to the study.

Similar results were realized for ACR50 — 38% of patients receiving 15 mg doses and 43% of patients receiving 30 mg doses achieved ACR50 compared to just 15% of patients receiving placebo.

ACR70 responses were achieved by 21% and 27% of patients in the 15 mg and 30 mg groups, respectively, compared to 6% of patients receiving placebo.

48% of patients receiving either dose of upadacitinib were able to achieve low disease activity, while only 17% of patients receiving placebo achieved the same endpoint.

Finally, 31% of patients receiving the 15 mg dose of upadacitinib and 28% of patients receiving the 30 mg dose were able to achieve clinical remission, compared to 10% of patients who received placebo.

“Achieving the target low disease activity in nearly half of the patients by 12 weeks and doing so at both high and low dose levels is encouraging,” said Professor Gerd Burmester, professor of medicine, Department of Rheumatology and Clinical Immunology, Charité Berlin. “Current treatment recommendations recognize the importance of this clinical target for patients, as achieving low disease activity has remained an unmet need in rheumatoid arthritis.”

According to AbbVie, upadacitinib’s safety profile was consistent with that observed in the drug’s phase II trial. No new safety signals were detected. Serious adverse events were 4% in the 15 mg dose arm and 3% in the 30 mg dose arm, compared to 2% in placebo. No deaths were reported.

The company plans to continue testing the upadacitinib’s potential for the treatment of psoriatic arthritis, Crohn’s disease, ulcerative colitis and atopic dermatitis.