FDA Extends Review of AbbVie’s RINVOQ Supplemental New Drug Application for Active Psoriatic Arthritis Due to Safety Concerns

Compiled by LiLi

On March 17, foreign media reported that AbbVie announced the U.S. FDA had extended the review period for the supplemental new drug application (sNDA) of its anti-inflammatory drug RINVOQ for the treatment of adult patients with active psoriatic arthritis (PsA). The updated Prescription Drug User Fee Act (PDUFA) action date has been extended by three months to the end of the second quarter of 2021. As of the afternoon of March 17, AbbVie’s stock price fell more than 6% to $104.18.

AbbVie recently received information from the FDA requesting an updated assessment of the benefit-risk profile of RINVOQ for the treatment of psoriatic arthritis. AbbVie responded to this request, and the FDA will require additional time to conduct a comprehensive review of the submitted documents.

RINVOQ (upadacitinib) is an oral, once-daily, selective, reversible JAK inhibitor discovered and developed by AbbVie scientists for the treatment of various immune-mediated inflammatory diseases. The drug exhibits greater inhibitory activity against JAK1 compared to JAK2, JAK3, and TYK2.

The drug achieved success in a large-scale Phase III clinical study for the treatment of adult psoriatic arthritis (PsA) last year. The study was conducted in adult patients with active psoriatic arthritis who had an inadequate response to or were intolerant of one or more non-biologic disease-modifying antirheumatic drugs (DMARDs).

This study was a multicenter, randomized, double-blind, parallel-group, active-drug and placebo-controlled Phase III trial conducted in 1,705 adult patients with psoriatic arthritis (PsA) who had an inadequate response to at least one non-biologic DMARD. It evaluated the efficacy and safety of two doses of Rinvoq (15 mg and 30 mg, once daily) compared with placebo and adalimumab. Patients were randomized to receive Rinvoq 15 mg, Rinvoq 30 mg, adalimumab (40 mg every other week [EOW]), or placebo. The primary endpoint was the proportion of patients achieving an ACR20 response at Week 12 in the two Rinvoq dose groups compared with the placebo group. Secondary endpoints included the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 12, the proportion of patients achieving PASI75 (≥75% improvement in the Psoriasis Area and Severity Index) at Week 16, and the proportion of patients achieving Minimal Disease Activity (MDA) at Week 24.

Data showed that the study met its primary endpoint: at Week 12, 71% and 79% of patients in the 15 mg and 30 mg groups, respectively, achieved an ACR20 response, compared with 36% in the placebo group (p < 0.0001). In comparison with adalimumab, both doses of Rinvoq demonstrated non-inferiority in ACR20 response rates at Week 12, with superiority observed only for the 30 mg dose. At Week 12, the ACR50 response rates were 38%, 52%, and 13% in the 15 mg, 30 mg, and placebo groups, respectively (nominal p < 0.0001). At Week 12, the ACR75 response rates were 16%, 25%, and 2% in the 15 mg, 30 mg, and placebo groups, respectively (nominal p < 0.0001).

Based on HAQ-DI assessments, patients treated with Rinvoq demonstrated substantial improvements in physical function at Week 12: the mean changes from baseline in HAQ-DI scores were -0.42 and -0.47 for the 15 mg and 30 mg Rinvoq groups, respectively, compared with -0.14 for the placebo group (p<0.0001). At Week 16, Rinvoq also showed improvement in skin symptoms, with 63% and 62% of patients in the 15 mg and 30 mg Rinvoq groups, respectively, achieving PASI75, versus 21% in the placebo group (p<0.0001). The proportions of patients achieving MDA at Week 24 were 37% and 45% in the 15 mg and 30 mg Rinvoq groups, respectively, compared with 12% in the placebo group (p<0.0001). After 24 weeks of treatment, both 15 mg and 30 mg doses of Rinvoq significantly inhibited radiographic progression compared with placebo (p<0.01, assessed by change from baseline in the PsA-modified Sharp/van der Heijde score). Inhibition of joint damage is important in patients with psoriatic arthritis, as it impacts physical function and disability. The safety profile of Rinvoq in this study was consistent with previously reported data, with no new safety risks identified.

In August 2019, RINVOQ received the world’s first approval in the United States for adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. RINVOQ also received approval from the European Commission for adult patients with moderately to severe RA who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs), as well as for the treatment of active psoriatic arthritis (PsA) and active ankylosing spondylitis (AS) in such adult patients.

The approved dose of RINVOQ for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis is 15 mg. Currently, AbbVie is developing Rinvoq for the treatment of various inflammatory diseases, with Phase III clinical trials underway for psoriatic arthritis (PsA), rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), Crohn's disease (CD), atopic dermatitis (AD), ulcerative colitis (UC), and giant cell arteritis (GCA).

The industry holds a very optimistic view of Rinvoq’s commercial prospects. EvaluatePharma, a pharmaceutical market research firm, previously released a report predicting that Rinvoq’s global sales would reach $2.57 billion in 2024, making it the fifth best-selling anti-rheumatic drug worldwide.

Additionally, AbbVie has received a similar request from the FDA regarding the supplemental new drug application for the use of RINVOQ in the treatment of atopic dermatitis, which is currently being prepared and will be submitted to the FDA shortly.

Reference Sources:

1.AbbVie Announces Extension of Review for Supplemental New Drug Application of Upadacitinib for the Treatment of Adults with Active Psoriatic Arthritis

2.RINVOQ (upadacitinib) Meets Primary and Key Secondary Endpoints in Phase 3 Study in Psoriatic Arthritis

3.FDA extends review period for Rinvoq sNDA