AbbVie Gains FDA Approval for Upadacitinib, Its Successor to Humira

Drug maker AbbVie has received approval for upadacitinib (Rinvoq), an orally administered Janus kinase (JAK) inhibitor for the treatment of patients with rheumatoid arthritis (RA) who have not responded adequately to methotrexate.

AbbVie expects the drug to become available to US patients later this month. The small-molecule drug, given at a dose of 15 mg once daily, will launch at a list price of $59,000 per patient per year, under the approximately $60,000 per patient per year for AbbVie’s flagship RA therapy, adalimumab (Humira). AbbVie said in a statement that its patient support program and copay card may bring out-of-pocket costs for eligible commercially-insured patients to $5 per month.

Upadacitinib is expected to help AbbVie continue to lead in the immunology market after biosimilar competition emerges for adalimumab in 2023. The approval for the treatment of RA is one of 6 indications that AbbVie’s chief executive officer, Richard Gonzalez, said in a 2018 presentation that the company expects to have approved and launched by 2022.

Upadacitinib was approved on the basis of data from the SELECT program, which enrolled approximately 4400 patients in 5 studies.

In one of those studies, the SELECT-COMPARE study, upadacitinib outperformed both placebo and AbbVie’s blockbuster brand-name adalimumab, Humira, in terms of the proportion of patients who achieved the American College of Rheumatology’s criteria for 20% improvement (ACR20) at week 12. The JAK inhibitor was also superior to adalimumab in terms of the proportion of patients who reached ACR50 at week 12, as well as in reduction of pain and improvement in quality of life as measured by the Health Assessment Questionnaire Disability Index.

The proportion of patients with adverse events (AEs) was higher for those given upadacitinib than those given placebo, but similar to those given adalimumab. Notably, thromboembolic events were similar across the 3 arms; 6 venous thromboembolic events occurred, 1 in the placebo arm, 2 in the upadacitinib arm, and 3 in the adalimumab arm. In a previous phase 3 study in the SELECT clinical program, SELECT-MONOTHERAPY, some concerns arose about the safety of the drug with respect to thromboembolic events.

In its label, upadacitinib carries a boxed warning that indicates that JAK inhibitors as a class have been liked with thrombosis; Pfizer’s tofacitinib (Xeljanz) was recently given a boxed warning on its label noting an increased risk for pulmonary embolism with a 10-mg twice-daily dose of the drug, which is currently approved for patients with ulcerative colitis. Baricitinib (Olumiant) also carries such a boxed warning, and was approved only at the lower of 2 proposed doses after the FDA’s Arthritis Advisory Committee voted against recommending approval of a higher dose given concerns about the potential for dose-dependent adverse events including thrombosis.