AbbVie recently announced that it has submitted a new indication application for the oral anti-inflammatory drug Rinvoq (upadacitinib, 15 mg once daily) to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) This medicine is a selective and reversible JAK inhibitor for the treatment of adult patients with active psoriatic arthritis (PsA).
Michael Severino, MD, Vice Chairman and President of AbbVie, said: "Psoriatic arthritis is a complex heterogeneous disease that manifests across multiple areas, including joints and skin, causing daily pain, fatigue and stiffness. We look forward to I work with the regulatory authorities and hope to bring Rinvoq to patients with this debilitating disease as soon as possible."
This new indication application is based on data from two Phase III clinical studies, SELECT-PsA-1 (NCT03104400) and SELECT-PsA-2 study (NCT03104374). These two studies enrolled more than 2000 patients with active PsA. The results showed that in both studies, Rinvoq reached the primary endpoint of ACR20 response compared to placebo. In addition, the 15 mg dose of Rinvoq and adalimumab showed non-inferiority in response to ACR20 at week 12 of treatment. Patients receiving Rinvoq also had greater improvements in physical function (HAQ-DI) and skin symptoms (PASI 75), and a greater percentage of patients achieved the lowest disease activity. Among PsA patients, the safety of Rinvoq is consistent with the results of the previously reported phase III rheumatoid arthritis clinical trial, and no new major safety risks have been found.
——SELECT-PsA-1: is a multicenter, randomized, double-blind, parallel group, positive drug and placebo-controlled phase III study in 1705 patients modified at least one abiotic disease anti-rheumatic drug (DMARD) Conducted in adult patients with under-responsive PsA, the efficacy and safety of two doses of Rinvoq (15 mg and 30 mg once daily) relative to placebo and adalimumab were evaluated. In the study, patients were randomly assigned to receive Rinvoq 15 mg, Rinvoq 30 mg, adalimumab (40 mg, every other week [EOW]), and placebo. The primary endpoint was the proportion of patients who achieved an ACR20 response at week 12 in the two-dose Rinvoq treatment group compared with the placebo group. Secondary endpoints include: change in the Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline at week 12, the proportion of patients who achieved PASI75 (psoriasis area severity index improvement by 75%) at week 16, and the lowest disease at week 24 Proportion of patients with activity (MDA).
The data showed that the study reached the primary endpoint: at week 12, 71% and 79% of patients in the 15 mg and 30 mg groups achieved ACR20 responses, respectively, and 36% in the placebo group (p<0.0001). When compared with adalimumab, the two doses of Rinvoq achieved non-inferiority in the ACR20 response rate at the 12th week of treatment, and only the 30 mg dose showed superiority. Regarding the ACR50 response rate at the 12th week of treatment, the 15 mg group, 30 mg group, and placebo group were 38%, 52%, and 13%, respectively (nominal p<0.0001). In terms of ACR75 response rate at the 12th week of treatment, 16%, 25%, and 2% in the 15 mg group, 30 mg group, and placebo group (nominal p<0.0001).
According to the measurement of the HAQ-DI score, the physical function of patients receiving Rinvoq also improved significantly at week 12: the HAQ-DI scores of patients in the 15mg and 30mg Rinvoq treatment groups changed from baseline by -0.42 and -0.47, respectively. The group change was -0.14 (p<0.0001). At week 16, Rinvoq also showed improvement in skin symptoms. Among patients receiving 15 mg and 30 mg doses of Rinvoq, 63% and 62% of patients achieved PASI75, respectively, and 21% of placebo (p<0.0001). The proportion of patients who achieved MDA at the 24th week of treatment was 37% and 45% in the 15 mg and 30 mg Rinvoq treatment groups, respectively, and 12% in the placebo group (p<0.0001). After 24 weeks of treatment, 15 mg and 30 mg of Rinvoq significantly inhibited radiological progression compared to placebo (p<0.01, assessed by change from baseline with PsA Sharp/van der Heijde score). The suppression of joint damage is important for patients with psoriatic arthritis because it affects physical function and disability. In the study, Rinvoq's safety was consistent with previous reports, and no new safety risks were found.
——SELECT-PsA 2: A multi-center, randomized, double-blind, parallel group, placebo-controlled study conducted in active PsA patients with insufficient response to at least one biological disease-modified anti-rheumatic drug (bDMARD), The aim is to evaluate the efficacy and safety of Rinvoq relative to placebo. In the study, patients were randomly assigned to receive Rinvoq 15 mg, Rinvoq 30 mg, and placebo. At week 24, they received oral Rinvoq 15 mg or Rinvoq 30 mg.
The primary endpoint of the study was the percentage of patients who achieved ACR20 remission after 12 weeks of treatment. Secondary endpoints included changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) from baseline, the proportion of patients who achieved ACR50 and ACR70 at week 12, and The proportion of PASI 75 reached at week 16 and the proportion of patients who reached the minimum disease activity (MDA) at week 24. The trial is ongoing and the long-term expansion trial is still blinded to assess the long-term safety, tolerability, and efficacy of 2 once-daily doses (15 mg and 30 mg) of Rinvoq in patients who have completed the placebo-controlled phase.
The results showed that both doses of Rinvoq (15 mg and 30 mg once daily) reached the primary endpoint of ACR20 remission at week 12 compared to placebo. In addition, the two doses of Rinvoq showed significantly greater relief at all secondary endpoints compared to placebo.
The specific data are: (1) At the 12th week of treatment, 57% and 64% of patients in the 15-mg and 30-mg Rinvoq treatment groups achieved ACR20 remission, respectively, and 24% in the placebo group (p<0.0001). (2) At the 12th week of treatment, 32% and 28% of patients in the 15-mg and 30-mg Rinvoq treatment groups achieved ACR50 remission, respectively, and 5% in the placebo group (p<0.0001). (3) At the 12th week of treatment, 9% and 17% of patients in the 15-mg and 30-mg Rinvoq treatment groups achieved ACR70 remission, respectively, and 0.5% in the placebo group (p<0.0001). (4) At the 12th week of treatment, the physical function (HAQ-DI evaluation) of the patients treated with Rinvoq was further improved. (5) Rinvoq-treated patients showed improvement in skin symptoms. In the 16th week of treatment, 52% and 57% of patients in the 15- and 30-mg Rinvoq treatment groups achieved PASI75 remission, respectively, and 16% in the placebo group (p<0.0001). (6) In the 24th week of treatment, 25% and 29% of patients in the 15- and 30-mg Rinvoq treatment groups achieved MDA, respectively, and 3% in the placebo group (p<0.0001). (7) In this study, Rinvoq's safety is consistent with previous research results, and no new safety risks have been found.
The active pharmaceutical ingredient of Rinvoq is upadacitinib, which is an oral selective and reversible JAK1 inhibitor discovered and developed by AbbVie. It is being developed to treat several immune-mediated inflammatory diseases. JAK1 is a kinase that plays a key role in the pathophysiology of various inflammatory diseases.
In August 2019, Rinvoq received the world's first batch for the treatment of moderately to severely active rheumatoid arthritis (RA) adults with insufficient or intolerant response to methotrexate (MTX). In December 2019, Rinvoq was approved by the European Union for the treatment of adults with moderate to severe RA who are under-responsive or intolerant to one or more disease-modified anti-rheumatic drugs (DMARD). In RA, the approved dose of Rinvoq is 15 mg.
Currently, Rinvoq treats psoriatic arthritis (PsA), RA, axial spondyloarthritis (axSpA), Crohn's disease (CD), atopic dermatitis (AD), ulcerative colitis (UC), Phase III clinical studies of cellular arteritis (GCA) are ongoing.
The industry is very optimistic about Rinvoq's business prospects. The pharmaceutical market research agency EvaluatePharma previously released a report predicting that Rinvoq's global sales in 2024 will reach 2.57 billion US dollars, making it the world's 5th best-selling anti-rheumatic drug.