FDA Accepts Upadacitinib New Drug Application for Rheumatoid Arthritis

Investigational daily oral therapy upadacitinib is a step closer towards marketing indication as a rheumatoid arthritis (RA) treatment.

The US Food and Drug Administration (FDA) has accepted and granted Priority Review to AbbVie’s New Drug Application (NDA) for upadacitinib as a therapy for adult patients with moderate to severe RA. The oral Janus kinase 1 (JAK1) inhibitor is currently being considered for multiple immunologic indications, but will receive FDA regulatory decision for RA in the second half of 2019.

AbbVie submitted the NDA with supporting data from the SELECT phase 3 program assessing the drug in 4000-plus adults with moderate to severe RA across 5 studies. The studies included efficacy, safety, and tolerability across a broad range of patients with RA. Investigators assessed for benefits in American College of Rheumatology (ACR) criteria responses, Disease Activity Score, and radiographic progression inhibition.

In data presented at the ACR/Association for Rheumatology Health Professionals (ARHP) Annual Meeting in Chicago last October, investigators from the phase 3 SELECT-MONOTHERAPY trial showed that patient-reported outcomes including joint pain, physical function, health-related quality of life, and morning stiffness were significantly improved in patients with moderate to severe RA who previously did not respond adequately to methotrexate.

The findings were particularly significant for these patients who had failed to report such improvements while on previous monotherapies such as methotrexate. Investigators noted that joint pain improvements were reported in some patients administered either 15 mg or 30 mg upadaticinib as soon as 2 weeks. By week 14, 65% and 69% on the therapy doses, respectively, had reported physical function improvements, compared to just 45% of those administered methotrexate (P < .001).

The SELECT-MONOTHERAPY trial, like the 4 other phase 3 studies included in the upadaticinib NDA, showed the therapy met its primary and ranked secondary endpoints.

“These results show that the improvements in clinical symptoms are accompanied by improvement in outcomes important to patients,” AbbVie vice president of Global Immunology Development Marek Honczarenko, MD, PhD, said at the time. “These results reinforce upadacitinib's therapeutic potential across diverse rheumatoid arthritis patient populations and its use as a monotherapy treatment option."

The therapy is also currently being explored as a treatment for atopic dermatitis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis in phase 3 trials.