AbbVie’s New Drug Application (NDA) for upadacitinib for the treatment of adult patients with moderate-to-severe rheumatoid arthritis (RA) has been granted priority review by the FDA, according to a press release.
RA affects an estimated 23.7 million individuals worldwide. Although methotrexate is commonly used as a first-line therapy, many patients do not respond to or cannot tolerate the therapy.
Upadacitinib is an investigational, once-daily oral Janus kinase 1-selective inhibitor. The NDA is supported by data from the phase 3 SELECT trial program evaluating more than 4000 patients with moderate-to-severe RA across 5 studies. These studies included assessments of efficacy, safety, and tolerability across a broad range of patients with RA.
In the first phase of the fifth pivotal SELECT-EARLY
phase 3 study, patients were randomized to receive upadacitinib 15 mg or 30 mg daily, or methotrexate. At both doses, upadacitinib monotherapy met the primary endpoints of ACR50 at week 12, and clinical remission at week 24 versus methotrexate. At week 12, 52% and 56% of patients who received 15 mg and 30 mg of upadacitinib, respectively, achieved ACR50, compared with 28% of patients who received methotrexate.
Clinical remission was achieved by 36% and 41% of patients in the 15 mg and 30 mg groups, respectively, compared with 14% of patients receiving methotrexate at week 12. Additionally, low disease activity based on DAS28(CRP) was achieved by 53% and 55% of patients in the 15 mg and 30 mg groups, respectively, compared with 28% of patients receiving methotrexate at week 12.
Following 24 weeks of treatment, both doses of upadacitinib monotherapy significantly inhibited radiographic progression as measured by the change in modified total Sharp score from baseline compared with methotrexate.
The trial included a Japan sub-study, in which subjects were randomized to receive upadacitinib 7.5 mg, 15 mg, 30 mg daily or methotrexate. In all SELECT phase 3 studies, upadacitinib met all primary and ranked secondary endpoints, according to AbbVie.
In this study, the safety profile of upadacitinib was consistent with previously reported results from the other SELECT trials in RA. The most common serious adverse events were infections.
Phase 3 trials of upadacitinib are also ongoing in atopic dermatitis, psoriatic arthritis, Crohn disease, and ulcerative colitis, according to the press release. It is also being investigated to treat ankylosing spondylitis.
AbbVie anticipates a regulatory decision in Q3 2019, according to the press release.
AbbVie Announces New Drug Application Accepted for Priority Review by US FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis [news release]. AbbVie. https://news.abbvie.com/news/press-releases/abbvie-announces-new-drug-application-accepted-for-priority-review-by-us-fda-for-upadacitinib-for-treatment-moderate-to-severe-rheumatoid-arthritis.htm?view_id=3018
. Accessed February 19, 2019.
Upadacitinib Monotherapy Meets All Primary and Ranked Secondary Endpoints Versus Methotrexate in a Phase 3 Study in Rheumatoid Arthritis [news release]. AbbVie. https://news.abbvie.com/news/upadacitinib-monotherapy-meets-all-primary-and-ranked-secondary-endpoints-versus-methotrexate-in-phase-3-study-in-rheumatoid-arthritis.htm
. Accessed February 19, 2019.