Investigational RA Drug Meets Phase 3 Study Endpoints

AbbVie recently announced promising findings from the phase 3 SELECT-NEXT trial that investigated the efficacy of investigational upadacitinib, an oral JAK1-selective inhibitor, in patients with moderate-to-severe rheumatoid arthritis (RA), according to a press release.

Upadacitinib achieved the trial’s primary endpoints of ACR20 and reduced disease activity among patients with RA who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs, according to AbbVie.

Secondary endpoints, including ACR50, ACR70, and clinical remission, were also met, AbbVie reported.

After 12 weeks of therapy with upadacitinib, 64% of patients treated with the 15-mg dose and 66% of patients treated with the 30-mg dose achieved ACR20, according to the release. Only 36% of placebo-treated patients reached this endpoint.

For ACR50, 38% and 43% of the 15-mg and 30-mg achieved the endpoint, respectively. In comparison, 15% of patients in the placebo cohort achieved ACR50.

Additionally, 21% of the 15-mg cohort and 27% of the 30-mg cohort reached ACR70, respectively, while only 6% of placebo-treated patients achieved this benchmark, AbbVie reported.

Overall, 48% of all upadacitinib-treated patients achieved low disease activity compared with 17% of placebo-treated patients.

"Achieving the target of 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 Gerd Burmester, MD, 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."

The researchers reported that 31% of the 15-mg group and 28% of the 30-mg group achieved clinical remission compared with 10% of the placebo cohort, according to the release.

The safety profile was consistent with phase 2 clinical trials, with no new safety signals detected.

AbbVie reported they are continuing to study the use of upadacitinib in other autoimmune conditions, including psoriatic arthritis, Crohn’s disease, ulcerative colitis, and atopic dermatitis, according to the release.

"We are excited by these promising results for upadacitinib. 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, AbbVie. "We are especially encouraged by the results on the more stringent measures of efficacy, such as ACR70, low disease activity and clinical remission. We look forward to seeing the full results from our phase 3 program."