Skyrizi (Risankizumab) Demonstrates Significant Improvement in Signs and Symptoms of Psoriatic Arthritis in Phase 3 Clinical Trials

November 7, 2021 /BioonBIOON/ -- AbbVie recently presented pooled data from two pivotal Phase 3 clinical trials (KEEPsAKE-1 and KEEPsAKE-2) at the 2021 American College of Rheumatology (ACR) Annual Meeting. These two studies evaluated the efficacy and safety of the novel anti-inflammatory IL-23 inhibitor Skyrizi (risankizumab) in adult patients with active psoriatic arthritis (PsA). Data show that,At 24 weeks of treatment, patients receiving Skyrizi demonstrated significant improvement in PsA symptoms and signs compared with placebo. No new safety signals were identified in the pooled analysis.

Specifically, at Week 24 of treatment, compared with the placebo group, the Skyrizi treatment groupA significantly higher proportion of patients achieved an ACR20 response (55.5% vs 31.3%). In addition, compared with the placebo group, patients in the Skyrizi treatment groupDemonstrated greater improvement in key clinical and patient-reported outcome endpoints.

In the pooled data, the safety profile of Skyrizi was generally consistent with that observed in patients with psoriasis, with no new safety signals identified. Serious treatment-emergent adverse events (TEAEs) occurred in 4.4% and 3.0% of patients in the Skyrizi and placebo groups, respectively; serious infections in 1% and 1.6%, respectively; and discontinuations due to adverse events in 0.8% and 1.4%, respectively. There was one death in the Skyrizi treatment group, assessed by the investigator as unrelated to the study drug, and one major adverse cardiovascular event (MACE) was reported.

Many PsA patients continue to experience significant symptoms, including joint pain, skin redness and scaling, and other manifestations of the disease.Data from this pooled analysis show that Skyrizi has the potential to provide a valuable treatment option, helping patients achieve meaningful relief from the symptoms and signs of PsA.

Currently, the new indication application for Skyrizi for the treatment of PsA is under review by the U.S.FDAand the review by the European Medicines Agency (EMA). In October this year, the EMA's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending the approval of Skyrizi: administered via subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter, as monotherapy or in combination with methotrexate (MTX), for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response to or are intolerant of one or more disease-modifying antirheumatic drugs (DMARDs). The European Commission (EC) is expected to make a final review decision by the end of this year.

If approved, this would be the second indication for Skyrizi. In 2019, Skyrizi was approved in the United States and the European Union for the treatment of adult patients with moderate to severe plaque psoriasis.

PsA is a systemic inflammatory disease affecting the skin and joints, affecting approximately 30% of patients with psoriasis. In pivotal Phase 3 studies,Patients treated with Skyrizi receive 4 maintenance doses annually following 2 initial doses. Compared with placebo, Skyrizi significantly improved skin and joint symptoms and physical function, with a higher proportion of patients achieving minimal disease activity.

The application for the new indication of Skyrizi for the treatment of PsA is based on data from two pivotal Phase 3 clinical trials (KEEPsAKE-1 and KEEPsAKE-2). These trials were conducted in adult patients with active PsA, and the enrolled patients included adult patients with active PsA who had an inadequate response to or intolerance of biologic and/or non-biologic disease-modifying antirheumatic drugs (DMARDs).

The results showed that,Compared with the placebo group, a significantly higher proportion of patients in the Skyrizi (150 mg) treatment group achieved the primary endpoint of ACR20 response at Week 24: in two studies, at Week 24 of treatment, 57% and 51% of patients in the Skyrizi treatment group achieved an ACR20 response, compared with 34% and 27% in the placebo group, respectively (p < 0.001).

Regarding secondary endpoints:At Week 24 of treatment, compared with the placebo group, the Skyrizi treatment group showed significant improvements in skin clearance (measured by at least 90% improvement in the Psoriasis Area and Severity Index [PASI 90]), physical function (measured by the Health Assessment Questionnaire-Disability Index [HAQ-DI]), and minimal disease activity (MDA).

In the KEEPsAKE-1 study, the PsA Sharp/van der Heijde score (PsA mTSS) at the secondary endpoint of Week 24 was 0.23 and 0.32 for the Skyrizi and placebo groups, respectively (p=0.496 [Note: lower scores indicate slower radiographic progression]). In both studies, the safety profile of Skyrizi was generally consistent with that observed in the treatment of plaque psoriasis, with no new safety risks identified.

The active pharmaceutical ingredient of Skyrizi is risankizumab, a monoclonal antibody that selectively blocks the immune-inflammatory mediator interleukin-23 (IL-23) in the body by specifically targeting the IL-23p19 subunit. IL-23 is a cytokine believed to play a pivotal role in numerous chronic immune-mediated diseases. Risankizumab was originally developed by the German pharmaceutical company Boehringer Ingelheim (BI), and AbbVie acquired the global commercialization rights to risankizumab in February 2016 by paying an upfront fee of $600 million.

In 2019, Skyrizi was approved in the United States and the European Union for the treatment of adult patients with moderate to severe plaque psoriasis. Currently, Skyrizi is in Phase III clinical trials for the treatment of Crohn's disease and psoriatic arthritis. Additionally, AbbVie is also evaluating Skyrizi for the treatment of ulcerative colitis and other inflammatory andImmunologyDisease.

Skyrizi is entering a highly crowded market, where it will compete with multiple drugs, including:NovartisCosentyx and Ilaris,Eli Lilly's Taltz, Valeant's Siliq, Johnson & Johnson's Tremfya, Sun Pharmaceutical's Ilumya, etc. Among these drugs, Tremfya and Ilumya are also biologic therapies that selectively target IL-23.

However, despite facing all these competitors, Skyrizi delivered robust sales performance, with global sales reaching $1.59 billion in 2020, representing a year-over-year increase of over 100%. With a series of Phase 3Clinical Trialsuccess, AbbVie optimistically projects that sales of Skyrizi and another oral anti-inflammatory JAK inhibitor, Rinvoq, will reach $15 billion in 2025, which will be able to offset the decline that flagship product Humira (adalimumab) has been facing in the U.S. market since 2023BiosimilarSales losses due to competition. (Bioon.com)

Original Source:AbbVie Presents Integrated Efficacy and Safety Data From Two Phase 3 Trials on Risankizumab (SKYRIZI) in Psoriatic Arthritis at ACR Convergence 2021