Ahead of US Biosimilar Competition for Humira, FDA to Give AbbVie's Upadacitinib Priority Review

AbbVie has announced that the FDA has accepted for priority review its New Drug Application for upadacitinib for the treatment of rheumatoid arthritis (RA). Upadacitinib is a proposed once-daily, small-molecule, oral Janus kinase inhibitor that, if approved, could be an alternative to therapy with such injectable biologics as AbbVie’s flagship RA treatment, adalimumab (Humira), which will face biosimilar competition in the United States by 2023.
Kelly Davio
February 20, 2019
AbbVie has announced that the FDA has accepted for priority review its New Drug Application (NDA) for upadacitinib for the treatment of rheumatoid arthritis (RA). Upadacitinib is a proposed once-daily, small-molecule, oral Janus kinase (JAK) inhibitor that, if approved, could be an alternative to therapy with such injectable biologics as AbbVie’s flagship RA treatment, adalimumab (Humira), which will face biosimilar competition in the United States by 2023.

AbbVie has long reassured investors that upadacitinib will help the company continue to lead in the immunology market after biosimilars of adalimumab reach the United States. In a 2018 presentation, Richard Gonzalez, chairman of the board and chief executive officer of AbbVie, said that upadacitinib—which AbbVie expects to launch in 6 indications by 2022, beginning with RA in 2019—will help the company’s immunology leadership to “…evolve from a single product to a portfolio of therapies.”

The NDA for the drug is supported by data from 5 of the 6 phase 3 SELECT trials in RA, which cumulatively enrolled more than 4900 patients with moderate to severe RA.

In October 2018, results of the phase 3 SELECT-COMPARE trial, presented during the American College of Rheumatology’s 2018 annual meeting, showed that upadacitinib outperformed both placebo and adalimumab in treating RA.1 The study met its primary end points of noninferiority and superiority of upadacitinib versus adalimumab at week 12 and radiographic inhibition for upadacitinib versus placebo at week 26. In the trial, the proportion of patients with adverse events (AEs) was higher for those given upadacitinib than those given placebo, but similar to those given adalimumab.

However, a patient death in the phase 3 SELECT-MONOTHERAPY trial dampened some enthusiasm about the product; while the study met all of its primary and key secondary end points, 1 patient taking a 15-mg dose of the study drug had a fatal hemorrhagic stroke caused by a ruptured aneurysm. There was also 1 event of pulmonary embolism in the study, also in a patient taking a 15-mg dose.

JAK inhibitors have, as a class, come under some scrutiny for their potential for AEs; in April 2018, the FDA’s Arthritis Advisory Committee voted to recommend a low dose of Eli Lilly’s JAK inhibitor, baricitinib, but voted against recommending approval of a higher dose given concerns about the potential for dose-dependent AEs such as thrombosis.

AbbVie says that it anticipates an FDA decision on upadacitinib in the third quarter of 2019.

Reference
1. Fleischmann R, Pangan AL, Mysler E, et al. A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Presented at: American College of Rheumatology 2018 Meeting; October 19-24, 2018; Chicago, Illinois. Abstract 890. acrabstracts.org/abstract/a-phase-3-randomized-double-blind-study-comparing-upadacitinib-to-placebo-and-to-adalimumab-in-patients-with-active-rheumatoid-arthritis-with-inadequate-response-to-methotrexate/.

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