Boehringer Ingelheim has achieved a landmark regulatory milestone with the FDA approval of Spevigo (spesolimab), establishing the first-ever approved therapy for generalized pustular psoriasis (GPP) flares. This IL-36 receptor inhibitor represents a breakthrough in treating the devastating eruptions of painful blisters that characterize this rare and life-threatening skin disorder.
The approval addresses a critical unmet need in dermatology, where GPP flares can lead to severe complications including heart failure, renal failure, and sepsis. Historical data indicates mortality rates following GPP flares range from 2% to 16%, with septic shock and cardiorespiratory failure being the primary causes of death.
Compelling Clinical Evidence
The FDA's decision was supported by data from the pivotal EFFISAYIL 1 trial, which demonstrated remarkable efficacy. In this study of 53 patients presenting with GPP flares, a single intravenous dose of spesolimab achieved complete pustule clearance in 54% of treated patients within one week, compared to only 6% in the placebo group. Notably, the therapeutic effect persisted for up to 12 weeks post-treatment.
Dr. Mark Lebwohl of the Icahn School of Medicine at Mount Sinai, who led the EFFISAYIL 1 trial, characterized the approval as a "turning point" in GPP treatment. "We now have an FDA-approved treatment that may help make a difference for our patients who, until now, have not had any approved options to help manage GPP flares," he stated.
Current Treatment Landscape and Future Developments
Prior to Spevigo's approval, clinicians relied on off-label use of various cytokine inhibitors, including TNF, IL-17, and IL-23 inhibitors, despite limited evidence supporting their effectiveness in GPP. Spevigo's approval as the first IL-36 inhibitor to reach the market represents a significant therapeutic advancement.
Boehringer Ingelheim is expanding the clinical investigation of spesolimab through two additional studies: EFFISAYIL-2, examining its potential as a maintenance treatment to prevent GPP flares, and EFFSAYIL-ON, a five-year extension study evaluating long-term efficacy and safety. The company is also exploring spesolimab's potential in other skin conditions, including palmoplantar pustulosis and hidradenitis suppurativa.
Market Access and Competition
While Boehringer Ingelheim has confirmed Spevigo's immediate availability, they have not disclosed the list price, indicating ongoing negotiations with insurance companies to ensure broad access. The company faces potential future competition from AnaptysBio's imsidolimab, another IL-36 inhibitor currently in phase 3 testing for GPP, with results expected in late 2023.
The European regulatory review of Spevigo is currently underway, with a decision anticipated before year-end, potentially expanding access to this innovative therapy for GPP patients globally.
