Spevigo Adverse Reactions

Summary of the safety profile: The safety data provided in the following are based on Effisayil-1, a double-blind, randomised trial comparing a single intravenous 900 mg dose of SPEVIGO (n=35) with placebo (n=18) in patients with generalized pustular psoriasis for up to 12 weeks after treatment and four double-blind, placebo-controlled trials of 254 spesolimab-treated patients who received doses up to 1200 mg intravenous or subcutaneous spesolimab for other diseases.
The most frequent adverse reactions associated with SPEVIGO are infections.
Tabulated summary of adverse reactions: (See Table 2.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Infections: During the 1-week placebo-controlled period in Effisayil-1, infections were reported in 17.1% of patients treated with SPEVIGO compared with 5.6% of patients treated with placebo. Serious infection (urinary tract infection) was reported in 1 patient (2.9%) in the SPEVIGO group and no patients in the placebo group. Infections observed in clinical trials with spesolimab were generally mild to moderate with no distinct pattern regarding pathogen or type of infection.
Injection site reactions: Injection site reactions include injection site erythema, injection site swelling, injection site pain, injection site induration, and injection site warmth. Injection site reactions were typically mild-to-moderate in severity.
Immunogenicity: As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
In patients with GPP treated with Spesolimab in Effisayil-1, anti-drug antibodies (ADA) formed with a median onset of 2.3 weeks. Following administration of i.v. spesolimab 900 mg, 24% of patients had a maximum ADA titer greater than 4000 and were Neutralising antibody (Nab)-positive by end of the trial (Weeks 12 to 17).
Females appeared to have higher immunogenicity response; the percentage of patients with ADA titer greater than 4000 was 30% in females, and 12% in males, respectively.
In some patients with ADA titer values greater than 4000, plasma spesolimab concentrations were reduced, with no apparent impact on pharmacokinetics at ADA titers below 4000. There are limited data on the impact of ADAs on safety and efficacy upon retreatment as the majority of subjects did not experience a subsequent, new flare in an open-label extension trial. There was no apparent correlation between the presence of ADA to spesolimab and hypersensitivity reactions.