AbbVie Announces Positive Top-Line Phase 3 Results for Upadacitinib in RA

Global pharmaceutical company AbbVie has announced positive top-line results from its phase 3 clinical trial evaluating upadacitinib (ABT-494), an investigational janus kinase 1 or JAK1-selective inhibitor. The trial studied the drug as a once-a-day oral therapy at doses of 15 mg and 30 mg, and was conducted in patients diagnosed with moderate-to-severe rheumatoid arthritis (RA) who did not respond adequately to treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Doses of both 15 mg and 30 mg achieved all primary and secondary study endpoints with high statistical significance, and the results demonstrated consistency with the safety profile observed in the drug’s phase 2 trials.

After 12 weeks of treatment, both doses of the agent met the study’s primary endpoints of low disease activity and ACR20, or the American College of Rheumatology 20% improvement 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.

Secondary endpoints included ACR50 and ACR70 (a 50% improvement and 70% improvement in the above areas, respectively) as well as clinical remission.

The findings are as follows:

• Low Disease Activity reported in 48% of the 15-mg arm (n = 221) and 48% of the 30-mg arm (n = 219)
• ACR20 achieved in 64% (15-mg arm) and 66% (30-mg arm)
• ACR50 achieved in 38% (15-mg arm) and 43% (30-mg arm)
• ACR70 was achieved in 21% (15-mg arm) and 27% (30-mg arm)
• Clinical remission was reported in 31% (15-mg arm) and 28% (30-mg arm)

No new safety signals were detected in this trial, and serious adverse events were reported in 4% of the 15-mg arm and 3% of the 30-mg arm. No patient deaths were reported. AbbVie will present full trial results at an upcoming medical meeting and in a peer-reviewed journal.

"We are excited by these promising results for upadacitinib,” said Michael Severino, MD, executive vice president of research and development and chief scientific officer for AbbVie. “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.”AbbVie is also evaluating upadacitinib in several other immune-mediated conditions, including psoriatic arthritis, Crohn’s disease, ulcerative colitis, and atopic dermatitis.

AbbVie’s redoubled focus on upadacitinib may well be a response to its blockbuster drug adalimumab (Humira) recently losing patent protection. Though the compound patent for Humira expired last year, AbbVie has been defending a number of smaller patents related to the drug, including one patent, struck down by The Patent Trial and Appeal Board in May, that protected the drug for subcutaneous dosing in the treatment of RA. As rival manufacturer Coherus moves forward with its biosimilar adalimumab product (CHS-1420), AbbVie may be seeking to maintain its hold on the market for RA treatment with this innovative drug.