Tremfya And Taltz Provide PsA Highlights At EULAR
Executive Summary
The spotlight was on anti-interleukin drugs at the Madrid meeting last week, especially their role in advancing the treatment of psoriatic arthritis.
Johnson & Johnson’s Tremfya has moved closer to joining other interleukin inhibitors in the psoriatic arthritis (PsA) space after promising late-stage data of the drug was presented at the European League Against Rheumatism congress in Madrid.
The healthcare giant unveiled topline data on 14 June from the DISCOVER-1 and DISCOVER-2 Phase III trials of Tremfya (guselkumab) in adults with moderate to severe active PsA. In both studies, the IL-23 inhibitor hit its primary endpoint of American College of Rheumatology 20% improvement (ACR20) at week 24 compared with placebo; multiple secondary endpoints were also assessed that included ACR50 and 70, resolution of soft tissue inflammation, disease activity improvement in physical function, skin clearance and quality of life.
The full data set will be presented at upcoming medical meetings and will serve as the basis of PsA submissions to the US Food and Drug Administration and the European Medicines Agency later this year. Tremfya, which is partnered with MorphoSys AG, is already approved for psoriasis and is the follow-up to J&J’s IL-23/IL-12 inhibitor blockbuster Stelara. (Also see "ECLIPSE: J&J's Tremfya Beats Novartis' Cosentyx For Long-Term Psoriasis Clearance" - Scrip, 12 Dec, 2018.)
Tremfya was not the only IL-23 inhibitor to make waves at the Madrid meeting for PsA as Sun Pharmaceutical Industries Ltd. presented promising Phase II data on Ilumya (tildrakizumab). Some 71% of participants in the 450-patient trial who were on the drug, which was given pride of place at one of the EULAR official press conferences, achieved ACR20 response after 24 weeks and lead investigator Philip Mease of the University of Washington told journalists that the results demonstrated a clear separation between tildrakizumab and placebo as early as eight weeks (see sidebar).
Tremfya, Ilumya and - further back - AbbVie Inc.'s IL-23 inhibitor Skyrizi (risankizumab), which has recently been approved on both sides of the Atlantic for psoriasis, have a lot of catching up to do in PsA on the IL-17 inhibitors, principally Novartis AG’s Cosentyx (secukinumab). The Swiss major presented new data at EULAR from the MAXIMISE trial evaluating the drug in the management of axial manifestations of PsA and also provided a new analysis from the FUTURE 5 trial showing no radiographic progression in almost 90% of PsA patients, plus significant ACR20, 50 and 70 responses. (Also see "Novartis MAXIMISEs Cosentyx PsA Position" - Scrip, 13 Jun, 2019.)
However the IL-17 inhibitor that got the most attention at EULAR was Eli Lilly & Co.'s Taltz (ixekizumab), which is already approved for PsA. What caught the eye was the full data set from the Phase IIIb/IV SPIRIT-H2H head-to-head trial of Taltz and AbbVie's anti-TNF mega-blockbuster Humira (adalimumab).
In the trial, the first head-to-head between two biologics in the treatment of PsA, patients were randomized to receive Taltz (n=234) or Humira (n=231) for 52 weeks, with the primary analysis conducted at 24 weeks. PsA patients who met the study criteria for moderate to severe plaque psoriasis also received Taltz (n=49) or Humira (n=52) for their skin.
At 24 weeks, the proportion of patients achieving both a reduction in disease activity as defined by ACR50 as well as complete skin clearance (PASI 100) was 36% for Taltz and 28% for Humira. Breaking those figures down, Lilly noted that Taltz showed non-inferiority to Humira for the percentage of patients achieving ACR50 (51% vs. 47%) and superiority in terms of PASI 100 (60% vs. 47%).
The results came as no great surprise, given that IL-17 inhibition has been proved in trials across the board to be more effective at clearing the skin than the anti-TNFs, while the benefit in joint symptoms is less marked.
Nevertheless, Lilly will be hoping that the SPIRIT-H2H data are robust enough to persuade more doctors to plump for Taltz instead of Humira in PsA. Mease noted that "head-to-head data like these are significant and help inform treatment decisions. This study underscores that Taltz is an important option." This could prove tricky, not least on the financial front, given that the anti-TNFs, and more significantly their cheaper biosimilars, are now available in Europe, which is impeding take-up of the IL inhibitors as first-line treatment.
While Taltz is the first IL inhibitor to have head-to-head data against Humira in PsA, Cosentyx is following closely behind with the EXCEED study. Novartis began the trial in January last year evaluating Humira versus Cosentyx in over 800 biologic-naïve patients with PsA, with a primary endpoint of statistical superiority for ACR20 response rates at one year, and secondary endpoints including PASI90, ACR50 and resolution of enthesitis. EXCEED is expected to read out before the end of 2019. (Also see "Novartis' Cosentyx Goes Head-To-Head With Humira" - Scrip, 9 Jan, 2018.)