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FDA News Issue 11 May 2019

Published on 5/10/2019 4:04:00 PM


FDA Approves SKYRIZI (risankizumab-rzaa) for the Treatment of Moderate-to-Severe Plaque Psoriasis in Adults who are Candidates for Systemic Therapy or Phototherapy

On April 23, 2019, the US Food and Drug Administration (FDA) approved SKYRIZI (risankizumab-rzaa) for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The approved recommended dosage of SKYRIZI is 150 mg (two 75 mg injections) administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.
 
SKYRIZI may increase the risk of infections. Treatment with SKYRIZI should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SKYRIZI. Do not administer SKYRIZI to patients with active TB. Avoid use of live vaccines in patients treated with SKYRIZI. Additional information regarding these warnings and precautions can be found in the full prescribing information linked below.
 
Mechanism of Action (MOA) and Pharmacokinetics (PK)

  • MOA: Risankizumab-rzaa is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds to the p19 subunit of human interleukin 23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor. Risankizumab-rzaa inhibits the release of pro-inflammatory cytokines and chemokines.
  • General PK: Risankizumab-rzaa plasma concentrations increased dose-proportionally from 90 to 180 mg and from 18 to 300 mg (0.06 to 1.2 and 0.12 to 2.0 times the approved recommended dosage) following subcutaneous administration in subjects with plaque psoriasis and healthy subjects, respectively. Steady-state concentrations were achieved by Week 16. At the 150 mg dose, the estimated steady-state peak concentration (Cmax) and trough concentration (Ctrough) were approximately 12 mcg/mL and 2 mcg/mL, respectively.
  • Absorption: The absolute bioavailability of risankizumab-rzaa was estimated to be 89%. Cmax was reached by 3-14 days.
  • Distribution: The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%).
  • Elimination: The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and terminal elimination half-life was approximately 28 days.
  • Metabolism: The metabolic pathway of risankizumab-rzaa has not been characterized. As a humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.
  • Immunogenicity: By Week 52, approximately 24% (263/1079) of subjects treated with SKYRIZI at the recommended dose developed antibodies to risankizumab-rzaa. Of the subjects who developed antibodies to risankizumab-rzaa, approximately 57% (14% of all subjects treated with SKYRIZI) had antibodies that were classified as neutralizing. Higher antibody titers in approximately 1% of subjects treated with SKYRIZI were associated with lower risankizumab-rzaa concentrations and reduced clinical response.

Use in Specific Populations 
No clinically significant differences in the pharmacokinetics of risankizumab-rzaa were observed based on age (≥ 18 years). No specific studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of risankizumab-rzaa.
 
Risankizumab-rzaa clearance and volume of distribution increase and plasma concentrations decrease as body weight increases; however, no dose adjustment is recommended based on body weight.
 
Drug Interactions 
Risankizumab-rzaa has no clinically significant effect on the pharmacokinetics of drugs metabolized by cytochrome P450 (CYP)1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A when used concomitantly.

Efficacy and Safety 
Efficacy of SKYRIZI was demonstrated in multicenter, randomized, double-blind studies that enrolled subjects 18 years of age and older with moderate to severe plaque psoriasis. Additional information regarding efficacy trials can be found in the full prescribing information linked below.
 
The most common adverse reactions (≥ 1%) are upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.
 
Full prescribing information is available at https://go.usa.gov/xm554.


Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval. 

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

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