Spesolimab significantly improved signs and symptoms of flares in rare, life-threatening skin disease, generalized pustular psoriasis.

GPP is a rare, life-threatening neutrophilic skin disease, which is distinct from plaque psoriasis. It is characterized by episodes of widespread eruptions of painful, sterile pustules (blisters of non-infectious pus). There is a high unmet need for treatments that can rapidly and completely resolve the signs and symptoms of GPP flares. Flares greatly affect a person’s quality of life and can lead to hospitalization with serious complications, including heart failure, renal failure, sepsis, and death.

In the 12-week trial; 53 patients experiencing a GPP flare were treated with a single intravenous dose of spesolimab or placebo. Most patients at the outset of the trial had a high or very high density of pustules and impaired quality of life. Results after one week demonstrated that: i. 54% of patients treated with spesolimab showed no visible pustules, compared to 6% of those treated with placebo. ii. 43% of patients treated with spesolimab showed clear/almost clear skin, compared to 11% of those in the placebo group. iii. After one week of treatment, spesolimab was associated with a higher number of infections and systemic drug reactions compared to placebo.

For some patients, pustular and skin clearance were maintained for the duration of the study. This clearance was accompanied by clinically significant improvements in quality of life and symptoms such as pain and fatigue.

Adverse events were reported in 66% of patients treated with spesolimab and 56% of those receiving placebo after the first week. Infections were reported by 17% and 6% of patients in the spesolimab and placebo groups, respectively. Serious adverse events were reported in 6% of patients treated with spesolimab. Two patients receiving spesolimab were reported to have drug reactions with eosinophilia and systemic symptoms.

The clinical program for spesolimab includes two other trials that are currently underway. The Effisayil 2 study will assess the safety and efficacy of spesolimab for the treatment of GPP, including flare prevention and symptom control over 48 weeks. Effisayil ON is a five-year, open-label extension study that will provide additional long-term efficacy and safety data for spesolimab in the treatment of GPP.

The FDA has accepted a Biologics License Application and granted Priority Review for spesolimab for the treatment of generalized pustular psoriasis (GPP) flares. FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvement over available options in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. The FDA has granted spesolimab Orphan Drug Designation for the treatment of GPP, and Breakthrough Therapy Designation for spesolimab for the treatment of GPP flares in adults.

See-VOL. 385 NO. 26, DEC 23, 2021 W"Trial of Spesolimab for Generalized Pustular Psoriasis"- H. Bachelez and OthersN Engl J Med 2021; 385:2431-2440.