Risankizumab Demonstrates Superiority in Primary, Secondary Endpoints for Adults with Moderate to Severe Plaque Psoriasis in Head-to-head Phase 3 Trial Advances

Late-breaking data from a phase 3b open-label study showed risankizumab had superior rates of skin clearance to secukinumab over 52 weeks of treatment of moderate to severe plaque psoriasis.¹

Of the patients who received risankizumab, 66% achieved 100% clearance in the Psoriasis Area and Severity Index (PASI) at week 52 vs only 40% of those receiving secukinumab. This most recent update, presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2020, builds upon previously published results that also demonstrated risakizumab’s superiority at week 52.²

The IMMerge trial,² a phase 3, international multicenter, randomized, open-label, assessor-blinded comparator study, evaluated the safety and efficacy of risankizumab compared to secukinumab in the treatment of adults with moderate to severe plaque psoriasis. Patients were randomized (1:1) to receive either risankizumab 150 mg (two 75-mg subcutaneous injections at baseline and at 4 weeks, then subsequently every 12 weeks) or secukinumab 300 mg (two 150-mg subcutaneous injections at baseline and weeks 1, 2, 3, and 4, then every 4 weeks thereafter).

The study primary endpoints were noninferiority at week 16 (margin of 12%) and superiority at week 52, both at PASI 90, and ranked secondary endpoints were PASI 100, static Physician Global Assessment (sPGA) score of clear or almost clear (0/1), and PASI 75, all at week 52. Any missing data throughout the 52-week study period was imputed using nonresponder imputation.

Overall, the study included 327 adult patients with psoriasis, including 164 in the risankizumab arm and 163 in the secukinumab arm. Of the patients, 37.8% receiving risankizumab and 35.6% secukinumab had previous biologic use.³ Patients had a mean baseline PASI score of 19.8 ± 13.8 in the risankizumab group and 20.1 ± 8.06 in the secukinumab group, with sPGA scores of 3 (risankizumab, n=140; secukinumab, n=137) and 4 (risankizumab, n=24; secukinumab, n=25) for all patients.

At week 16 of treatment, 74% achieved PASI 90 at with risankizumab vs 66% with secukinumab; the adjusted difference using 96.25% CI was 8.2% (2.2, 18.6), effectively establishing noninferiority.

After 52 weeks, 87% of patients treated with risankizumab achieved PASI 90 compared with 57% treated with secukinumab (P<.001). Further, 66% of the risankizumab arm achieved PASI 100 vs 40% of secukinumab.

The trial also demonstrated the superiority of risankizumab compared with secukinumab for all ranked secondary endpoints (PASI 100, sPGA 0/1, PASI 75).

In the late-breaking research presentation at AAD VMX 2020, Richard B. Warren, BSc (Hons), MBChB (Hons), MRCP, PhD, noted that 151 (92.1%) patients who received risankizumab and 135 (82.8%) patients receiving secukinumab completed the study at week 52. Prof Warren highlighted that the number of patients receiving secukinumab was approximately 10% lower, explaining, "that's being driven by a slightly higher dropout related to adverse events and a higher dropout related to a lack of efficacy."³

Safety data from this trial was consistent with previously reported studies^4,5 with no new safety signals observed. The rate of adverse events (AEs) was similar between the two biologics; 71% of both treatment arms reported adverse events.¹ Common AEs included nasopharyngitis, upper respiratory tract infection, headache, arthralgia and diarrhea. Serious AE rate was 5.5% for risankizumab and 3.7% for secukinumab; however, AEs led to the discontinuation of the study biologic in 1.2% of patients receiving risankizumab compared with 4.9% receiving secukinumab.

The phase 3b study¹ also showed a significantly higher proportion of the risankizumab arm achieved sPGA 0/1 vs the secukinumab arm (88% vs 58%, respectively).

Risankizumab is an IL-23 inhibitor that selectively targets the p19 subunit. It gained FDA approval in April 2019.

References
1. AbbVie presents new late-breaking data showing SKYRIZI® (risankizumab-rzaa) achieves superior rates of complete skin clearance versus COSENTYX® (secukinumab) at 52 weeks. Press release. AbbVie; June 12, 2020. Accessed July 7, 2020. https://news.abbvie.com/news/press-releases/abbvie-presents-new-late-breaking-data-showing-skyrizi-risankizumab-rzaa-achieves-superior-rates-complete-skin-clearance-versus-cosentyx-secukinumab-at-52-weeks.htm
2. New head-to-head phase 3 data show Skyrizi™ (risankizumab) superior to Cosentyx®* (secukinumab) across primary and all ranked secondary endpoints in adults with moderate to severe plaque psoriasis at 52 weeks. Press release. AbbVie; January 14, 2020. Accessed July 7, 2020. https://news.abbvie.com/news/press-releases/new-head-to-head-phase-3-data-show-skyrizi-risankizumab-superior-to-cosentyx-secukinumab-across-primary-and-all-ranked-secondary-endpoints-in-adults-with-moderate-to-severe-plaque-psoriasis-at-52-weeks.htm
3. Warren RB. Risankizumab versus secukinumab in patients with moderate-to-severe plaque psoriasis: a phase 3 trial. Presented at: American Academy of Dermatology Virtual Meeting Experience 2020; June 10-12, 2020.
4. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-661. doi:10.1016/S0140-6736(18)31713-6
5. Reich K, Gooderham M, Thaçi D, et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019;394(10198):576-586. doi:10.1016/S0140-6736(19)30952-3