Upadacitinib Superior to Adalimumab in Phase 3 Trial in RA

This week, drug manufacturer AbbVie announced positive top-line results from its phase 3 SELECT-COMPARE clinical trial that investigated upadacitinib, a Janus kinase (JAK) inhibitor, versus placebo and versus adalimumab, an anti—tumor necrosis factor inhibitor, in patients with rheumatoid arthritis (RA).

AbbVie reports that the trial of 15 mg of orally-administered, once-daily upadacitinib met its primary endpoints, with 71% of patients achieving 20% improvement based on American College of Rheumatology criteria (ACR20), and 29% achieving clinical remission.

Furthermore, upadacitinib was superior to adalimumab on ranked secondary endpoints: at week 12, 45% of patients receiving upadacitinib achieved ACR50 (versus 29% of patients receiving adalimumab), and upadacitinib also demonstrated greater reductions of pain (measured by the Patient's Assessment of Pain) and greater improvements in physical function (measured by Health Assessment Questionnaire-Disability Index) at week 12. Upadacitinib also inhibited radiographic progression of RA versus placebo at week 26.

“These results show a significant impact on both signs and symptoms and radiographic progression compared to placebo, as well as improvements in important measures such as ACR response and low disease activity compared to adalimumab,” said Michael Severino, MD, executive vice president of research and development and chief scientific officer of AbbVie in a statement. “We are excited by these strong results which add to the body of evidence that support the potential of upadacitinib to be an important treatment option for patients with [RA].”

The safety profile of upadacitinib was consistent with previously reported results, and no new safety signals were detected. Through week 26, serious adverse events (AEs) occurred in 3.7% of patients receiving upadacitinib, 4.3% of patients receiving adalimumab, and 2.9% of patients on placebo. No deaths were reported in the upadacitinib group, but 2 deaths were reported in both the adalimumab group and the placebo group though week 26.

The positive data from this phase 3 trial continue to support AbbVie’s goal of finding a new foothold in the RA space after it loses its patent exclusivity for Humira, allowing biosimilars of the drug to enter the market. The reference adalimumab grossed $18 billion in sales last year, and one analyst believes that, should upadacitinib receive FDA approval, it could net around $6.5 billion in sales each year.

Despite positive results in this trial, a prior phase 3 study in the same clinical program, SELECT-MONOTHERAPY, raised questions about safety; 1 patient taking the study drug died of a hemorrhagic stroke, caused by a ruptured aneurysm. In the study, serious AEs occurred in 5% and 3% of patients receiving 15-mg and 30-mg doses of the drug, respectively.

Additional results of the SELECT trials will be presented at a future medical meeting, said AbbVie. According to a recent statement, the drug maker plans global regulatory submissions for upadacitinib for RA later this year.