# New and Emerging Treatments for Generalized Pustular Psoriasis: Focus on IL-36 Receptor Inhibitors
## 5 New Treatments for GPP
### Spesolimab
\begin{table}
\begin{tabular}{l l l l l l l} \hline \hline
**Trial** & **Study Design** & **Endpoints** & **Main Results** & **Main AEs** & **Main AEs** \\ \hline \multirow{6}{*}{Phase I} & - & Single-arm, open-label & Primary: & & & - & Mild to moderate \\  & - & 7 participants & - & Safety and tolerability & - & GPPGA 0/1 in 71\% of & - & Infectious \\  & - & Follow-up for 20 & & (\% AE) & & patients by Week 1 and in & - & Vomiting \\  & & weeks & & Secondary: & & 100\% of patients by Week & - & Pain \\  & - & SD of 10 mg/kg IV at & & - & GPPGA 0/1 at week 2 & & - & Infusion-related \\  & & baseline & & - & GPPGA 0/1 at week 2 & & - & reactions \\  & & & & & & - & No severe AE \\ \hline \multirow{6}{*}{Phase II} & - & Randomized, PC, DB & Primary: & & - & GPPGA Pustulation & \\  & - & 53 participants & - & GPPGA Pustulation & & subscore of 0 at Week 1 in & \\  & - & 12 weeks & & Subscore 0 at Week 1 & & 54\% of spesolimab and 6\% & - & Infections \\  & - & Randomized 2:1 into & Secondary: & & - & of placebo (\(p<\) 0.001) & - & Systemic symptoms \\  & & & & Secondary: & - & GPPGA total 0/1 in 43\% & - & Antidrug antibodies \\  & & placebo & - & GPPGA score of 0 or 1 & & of spesolimab and 11\% of & \\  & - & Randomized, PC, DB & & & & \\  & - & 123 participants & & & & & \\  & - & 48 weeks & Primary: & & - & Non-flat dose-response & - & Infections \\  & - & Randomized 1:1:1:1 & - & - & Time to first GPP flare & relationship for different & - & Injection-site erythema \\  & into: LD 600 mg, & - & - & - & groups when compared to & - & Arthralgias \\  & followed by & Secondary: & & & & & - & Spesolimab and placebo \\  & (Effisayil 2) & maintenance 300 mg & - & Occurrence of at least & - & Compared to placebo, & & groups with similar \\  & q4w; LD 600 mg, & - & 1 GPP flare & high-dose spesolimab & & incidence of AEs \\  & followed by & - & GPPCA score of 0 or 1 & & showed statistically & - & Spesolimab groups with \\  & q12w; LD 300 mg, & & & up to Week 48 & & significant superiority on & 10\% of serious AEs and \\  & followed by & & & & time to GPP (\(p=\) 0.0005) & & 3\% in placebo group \\  & maintenance 150 mg & & & & & & \\  & q12w; or placebo & & & & & \\ \hline \hline \end{tabular} AE—Adverse Event; DB—Double Blind; DLQI—Dermatology Quality of Life Index; GPP—Generalized Pustular Psoriasis; GPPGA—Generalized Pustular Psoriasis Physician Global Assessment; IV—Intravenous; LD—Loading Dose; PC—Placebo Controlled; q4w—every 4 weeks; q12w—every 12 weeks; SC—Subcutaneous; SD—Single Dose.  
\end{table} 
Table 1: Efficacy and safety data of spesolimab. at screening, published its results on evaluating the efficacy and safety of spesolimab for GPP flare prevention (Table 1). These patients were randomly assigned in a 1:1:1:1 ratio to a subcutaneous placebo group, a subcutaneous low-dose spesolimab group (300 mg loading dose followed by 150 mg every 12 weeks), a subcutaneous medium-dose spesolimab group (600 mg loading dose followed by 300 mg every 12 weeks), and a subcutaneous high-dose spesolimab group (600 mg loading dose followed by 300 mg every 4 weeks) The patients were followed for over 48 weeks [41]. To assess spesolimab's efficacy in preventing GPP flares as a maintenance treatment, this clinical trial analyzed the patients' time to develop the first flare by week 48, attempting to demonstrate a non-flat dose-response curve. If this was achievable, the secondary objective would be to evaluate the possible superiority of high-dose or medium-dose spesolimab over placebo. This evaluation would also involve analyzing the time to develop the first flare by week 48 and the occurrence of at least one GPP flare by the same time [41]. By Week 48 of the trial, 35 of the original 123 patients had experienced GPP flares: 16 in the placebo group (52%), 7 in the low-dose group (23%), 9 in the medium-dose group (29%), and 3 in the high-dose group (10%). These data demonstrated a non-flat dose-response relationship with statistical significance when comparing spesolimab to the placebo.