FDA Approves Upadacitinib (Rinvoq), New JAK Inhibitor for RA

Megan Brooks

August 19, 2019

The US Food and Drug Administration (FDA) has approved the oral Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) for adults with moderately to severely active rheumatoid arthritis (RA) who fail to respond adequately or are intolerant to methotrexate (MTX), according to a company news release.

Upadacitinib 15 mg is taken once daily. The company expects it to be available in the United States later this month and that its price will be $59,000 a year, according to a report in Reuters. AbbVie said it plans to offer a copay card that could reduce out-of-pocket costs to $5 per month for eligible, commercially insured patients. It also has a patient support program.

The efficacy, safety, and tolerability of upadacitinib for RA was studied in five phase 3 studies from the SELECT program. The studies enrolled a variety of RA patients, including those who experienced treatment failure with or were intolerant of biologic disease-modifying antirheumatic drugs (csDMARDs-IR) and who were naive to or who responded inadequately to methotrexate (MTX-IR).

Across the studies, upadacitinib met all primary and ranked secondary endpoints, the company said in its news release.

In SELECT-EARLY, at week 12, 52% of MTX-naive patients who were treated with upadacitinib had experienced an improvement of at least 20% in American College of Rheumatology criteria (ACR20), as compared with 28% who were treated with MTX. Upadacitinib is not indicated for methotrexate-naive patients.

In the SELECT-MONOTHERAPY study, at week 14, 68% of MTX-IR patients who were treated with upadacitinib had achieved ACR20, compared with 41% of those who continued with MTX .

In SELECT-COMPARE, at week 12, 71% of MTX-IR patients who were treated with upadacitinib plus MTX had achieved ACR20, as compared with 36% who were treated with placebo plus MTX.

In SELECT-NEXT, at week 12, 64% of csDMARD-IR patients who were treated with upadacitinib plus csDMARDs had achieved ACR20, compared with 36% of patients treated with placebo plus csDMARDs.

In SELECT-BEYOND, at week 12, 65% of biologic-IR patients who were treated with upadacitinib plus csDMARDs had achieved ACR20, as compared with 28% of those treated with placebo plus csDMARDs.

About 30% of patients treated with upadacitinib had achieved clinical remission, as assessed by disease activity score in 28 joints–C-reactive protein <2.6 (DAS28-CRP<2.6), at week 12 in SELECT-COMPARE and at week 14 in SELECT-MONOTHERAPY, compared with 6% of patients who received placebo plus MTX and 8% who received MTX. Durable remission rates were observed up to week 26, the company said.

The most common side effects associated with upadacitinib include upper respiratory tract infections, nausea, cough, and pyrexia.

The drug's label has warnings of a serious risk for serious infections and lymphoma.

The FDA recently added a black box warning to tofacitinib (Xeljanz, Pfizer) regarding an increased risk for pulmonary embolism and death, although the risk was associated with use of higher doses of the drug for ulcerative colitis. Tofacitinib is a JAK inhibitor.

"Despite the availability of multiple treatment options with varying mechanisms of action, many patients still do not achieve clinical remission or low disease activity — the primary treatment goals for rheumatoid arthritis," Roy M. Fleischmann, MD, primary investigator for SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center at Dallas, said in a news release from AbbVie.

"With this FDA approval, Rinvoq has the potential to help additional people living with RA achieve remission who have not yet reached this goal," he said.

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