Regulatory Decision Summary for Skyrizi

The efficacy of Skyrizi was assessed in 1,407 patients 18 years and older with active PsA in two phase 3, double blind, and placebo-controlled studies: 964 patients in KEEPSAKE1 and 443 patients in KEEPSAKE2. In both studies, patients were randomized to receive Skyrizi 150 mg or placebo at Weeks 0, 4, and every 12 weeks thereafter.

Patients had a diagnosis of PsA for at least 6 months, a median duration of PsA of 4.9 years, and active PsO or nail psoriasis at baseline. In KEEPSAKE1, all patients had a previous inadequate response or intolerance to non-biologic DMARD therapy (DMARD-IR) and were biologic naïve. In KEEPSAKE2, 53.5% of patients were DMARD-IR and 46.5% of patients had a previous inadequate response or intolerance to biologic therapy. In both studies, 59.6% of patients received concomitant methotrexate (MTX), 11.6% received concomitant non-biologic DMARDs other than MTX, and 28.9% received Skyrizi monotherapy.

The primary endpoint in both studies was the proportion of patients who achieved an American College of Rheumatology (ACR20) response at Week 24. Key secondary endpoints included ACR20/ACR50/ACR70 responses, Resolution of Enthesitis/Dactylitis, and Minimal Disease Activity at Week 24. Treatment with Skyrizi resulted in clinically meaningful and statistically significant improvements in measures of disease activity compared with placebo at Week 24. A clinically meaningful proportion of patients treated with Skyrizi vs. placebo had resolution of enthesitis and dactylitis at Week 24. Results from KEEPSAKE1 were suggestive of an inhibition of progression of structural damage and improvement in physical function with Skyrizi vs placebo at Week 24.

The primary and key secondary efficacy endpoints were achieved in the pivotal clinical trials. The benefits of Skyrizi were demonstrated in adults with active PsA.

In the PsA studies, 1,542 subjects received 1 or more dose of risankizumab with a median duration of 279 days. Of these, 464 subjects had 12 or more months of exposure to risankizumab. The most frequently reported treatment-emergent adverse events were upper respiratory tract infections at comparable rates in the risankizumab and placebo groups. The safety profile of Skyrizi in PsA is considered acceptable and not clinically meaningfully different from what has been reported in the previously authorized indication.

No relationship was observed between risankizumab exposure and percentage of subjects who experienced any adverse event (AE), serious adverse event (SAE), infection, or serious infection over the first 24 weeks.

Overall, the benefits outweigh the risks of Skyrizi in adult patients with active PsA. The benefit/risk profile of Skyrizi is considered favourable in the target patient population.