Regulatory Decision Summary for Skyrizi

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract characteristically associated with relapsing and remitting symptoms of abdominal pain, chronic diarrhea, weight loss, and fatigue. Symptoms present as acute periods of active symptoms (active disease or flare) among periods of quiescence (remission). CD is a progressive disease that can result in severe morbidity, including bowel damage, which may require surgery. Inflammation is typically segmental, asymmetrical, and transmural.

The benefits of Skyrizi are primarily demonstrated by two phase 3, multicentre, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy and safety of risankizumab as induction treatment (induction studies) in subjects with moderately to severely active CD, and a subsequent phase 3, multicentre, placebo-controlled study designed to evaluate the efficacy and safety of risankizumab as maintenance treatment (maintenance study) in subjects who achieved clinical response during the previous induction studies.

The induction studies demonstrated greater proportions of subjects receiving Skyrizi 600 mg IV compared to placebo as induction regimen achieved improvement in signs and symptoms of CD. Stool frequency and abdominal pain score (SF/APS) clinical remission and endoscopic response – including mucosal healing derived from ulcer-free endoscopy – at Week 12 favoured Skyrizi over placebo. The treatment response in favour of Skyrizi was observed independent of prior biologic or conventional therapy failure. Additional benefits in favour of Skyrizi were observed in health related quality of life assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ).

The maintenance study demonstrated greater proportions of subjects receiving Skyrizi 360 mg SC compared to placebo as maintenance regimen achieved SF/APS clinical remission and endoscopic response at Week 52 among those subjects who achieved SF/APS clinical response during induction regimen. Maintenance of clinical remission – clinical remission at Week 52 among subjects who achieved clinical remission at Week 0 – favoured SKYRIZI 360 mg SC relative to placebo.

Based on the data submitted, the safety profile of Skyrizi in subjects with CD is generally consistent with that previously established for subjects with psoriasis and psoriatic arthritis; however, hepatic adverse event(s) have emerged as a potential safety issue. The risk of hepatic adverse events will be monitored by pharmacovigilance measures as set out in the agreed upon post-market commitments.

Overall, based on the data evaluated as part of this submission, the BRDD considers the benefit-risk profile of Skyrizi to be favourable for the treatment of adults with moderately to severely active CD who had failed previous conventional or biologic therapies.

An updated Risk Management Plan (RMP) for Skyrizi was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Skyrizi has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications."

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

The overall, the benefit-harm-uncertainty profile is favourable for Skyrizi and the dosage strengths,360 mg/2.4 mL, 60 mg/mL for the recommended indication. A Notice of Compliance (NOC) was issued.

For further details about Skyrizi, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.