Oral Rheumatoid Arthritis Drug Achieves Positive Results in Phase 3 Trial

An oral rheumatoid arthritis (RA) drug achieved top-line results from a phase 3 trial of patients with moderate-to-severe RA, who did not adequately respond to treatment with conventional synthetic DMARDS (csDMARDs).

Upadacitinib is an oral investigational drug designed to selectively inhibit Janus kinases (JAK) enzymes, according to a press release.

The multicenter, double-blind, placebo-controlled, randomized phase 3 SELECT-NEXT trial was designed to evaluate the safety and efficacy of a 15-mg dose and a 30-mg dose of upadacitinib in adult patients with moderate-to-severe RA taking a stable dose of csDMARDs who had an inadequate response to treatment.

The primary endpoints of SELECT-NEXT was the percentage of participants who achieve an ACR20 response and low disease activity (LDA) after 12 weeks of treatment.

Key secondary endpoints included the proportion of patients who achieved ACR50 and ACR70 responses and clinical remission at 12 weeks, according to the release.

After 12 weeks, the results of the study showed that patients in both the 15-mg dose arm and the 30-mg dose arm met the primary endpoints. The key secondary endpoints were also achieved. The full results of the trial will be presented at an upcoming medical meeting and published in a peer-review publication.

“We are excited by these promising results for upadacitinib,” Michael Severino, MD, executive vice president of research and development and chief scientific officer at AbbVie, said in a release. “Selective inhibition of the JAK1 pathway may offer a novel treatment for rheumatoid arthritis patients who do not adequately respond to conventional therapies.

“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. AbbVie’s longstanding leadership in the treatment of immune-mediated diseases provides an opportunity to build upon our understanding and develop innovative therapies to address unmet patient needs.”

Findings at week 12 showed that 64% of participants administered the 15-mg oral, once-daily dose of upadacitinib and 66% participants administered the 30-mg dose achieved ACR20, compared with 36% who received the placebo.

Thirty-eight percent of patients in the 15-mg dose arm and 43% in the 30-mg arm achieved ACR50 responses compared with 15% of patients administered the placebo.

ACR70 responses were achieved by 21% and 27% of patients in the 15-mg and 30-mg groups, respectively, compared with 6% of pateints in the placebo arm, according to the release.

Forty-eight percent of patients administered either dose of upadacitinib achieved low disease activity, compared with 17% of patients administered the placebo. Clinical remission was achieved by 31% of pateints administered 15 mg of upadacitinib and 28% administered who received 30 mg, respectively, compared with 10% administered placebo.

The safety profile was found to be consistent with the phase 2 upadacitinib trials, and no new safety signals were observed. Serious adverse events occurred in 4% of patients in the 15-mg dose arm and 3% in the 30-dose mg arm, compared with 2% in placebo.

“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,” Gerd Burmester, professor of medicine, Department of Rheumatology and Clinical Immunology, Charité Berlin, said in the release. “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.”

Upadacitinib is currently being evaluated in ongoing phase 3 trials for the treatment of psoriatic arthritis. The drug is also being investigated to treat atopic dermatitis, Crohn’s disease, and ulcerative colitis, according to the release.