FDA regulatory application heralds a new contender in ankylosing spondylitis with AbbVie’s Rinvoq

Rinvoq has seen good news this last month with AbbVie’s announcement of topline results for Rinvoq (upadacitinib) in its second pivotal Phase III trial in atopic dermatitis, Measure Up 2, and now AbbVie has also submitted an application for FDA regulatory approval of its JAK inhibitor in adult patients with ankylosing spondylitis (AS), a serious form of axial spondyloarthritis (axSpA). The submission was made based on results of the pivotal Phase II / III SELECT Axis 1, where 52% of participants treated with Rinvoq achieved a 40% improvement in symptoms when measured by the Assessment of Spondyloarthritis International Society response criteria (ASAS40) at Week 14 compared to 26% in the placebo group. With an expected US launch date of 2023, GlobalData anticipates Rinvoq will accumulate 2028 sales of $113M in ankylosing spondylitis across the seven major markets (US, France, Germany, Italy, Spain, UK, and Japan).

The SELECT Axis 1 trial is a multicenter, randomised, double-blind, placebo-controlled study evaluating the safety and efficacy of Rinvoq in 187 patients with active ankylosing spondylitis who have responded inadequately to at least two different nonsteroidal anti-inflammatory drugs (NSAIDs) but have not yet been exposed to any form of biologic therapy. During the study, concomitant treatment with NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), or oral corticosteroids was allowed if the participants had been on a stable dose for at least 28 days prior to entering the study. Secondary endpoints examined participant response on a range of commonly used clinical scales, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). The safety profile of the drug was consistent with results in other studied indications. Although Rinvoq is widely expected to be prescribed as a third- or fourth-line therapy in the ankylosing spondylitis treatment algorithm, post-treatment with an anti-tumor necrosis factor (TNF) agent and Eli Lilly’s recent anti-interleukin (IL)-17 contender, Taltz (ixekizumab), the fact that AbbVie only recruited biologic-naïve patients in the SELECT Axis 1 study suggests that the company believes its drug has a chance at being prescribed to biologic-naïve patients, before market staples like the anti-TNFs and the anti-IL-17s. However, recommendations made in the 2019 update of the American College of Rheumatology’s (ACR) axSpA treatment guidelines suggest this will not be the case, as Pfizer’s Xeljanz (tofacitinib), another JAK inhibitor seeking approval in AS, is recommended as a treatment option only after a patient experiences primary or secondary nonresponse with an anti-TNF and then an anti-IL-17 drug.

On top of the treatment algorithm placing, Rinvoq will have to face other difficulties when entering the ankylosing spondylitis market. With Xeljanz and Galapagos’ filgotinib both aiming for an ankylosing spondylitis approval as well, Rinvoq is looking at fierce competition within its own drug class and will also have to contend with cheaper biosimilar options launching at various points in the next few years. Infliximab biosimilars are already available and adalimumab biosimilars will be launching in the US in 2023. However, AbbVie is already conducting a Phase III study, named SELECT Axis 2, that is examining the safety and efficacy of Rinvoq in patients with a milder form of axSpA, called non-radiographic axSpA (nr-axSpA). With approval in nr-axSpA, Rinvoq could substantially increase its patient pool, although it will still see competition in this patient segment from UCB’s Cimzia (certolizumab pegol), Novartis’ Cosentyx (secukinumab), and Taltz. Overall, Rinvoq has an uncertain future in the axSpA market.