Emerging Therapies in HS

Sonelokimab represents the newest IL-17 pathway inhibitor in development, utilizing nanobody technology to target both IL-17A and IL-17F with potentially enhanced tissue penetration due to its smaller molecular size. Phase 2 data demonstrated that approximately half of patients achieved HiSCR75, marking the first hidradenitis suppurativa (HS) trial to use this more stringent end point that better reflects clinically meaningful improvement and patient satisfaction. The nanobody structure may offer advantages in tissue penetration and potentially improved safety profile, though larger phase 3 studies will be necessary to confirm whether the cutaneous adverse events observed with other IL-17A/F inhibitors occur at similar rates.

The broader pipeline includes diverse mechanisms targeting various aspects of HS pathophysiology, reflecting growing understanding of disease heterogeneity. Combination IL-1α/β inhibitors, OX40 ligand costimulatory molecule blockers, and B-cell targeted therapies represent promising approaches for patients with treatment-refractory disease. Janus kinase (JAK) inhibitors from multiple companies are progressing through development with various selectivity profiles, offering oral treatment options with extensive safety databases from use in other inflammatory conditions.

Ongoing basic science research continues uncovering the roles of different immune pathways including IL-1α/β, B-cell switching mechanisms, and various T-cell populations, potentially enabling future biomarker-driven treatment selection. This research may ultimately allow matching specific therapies to individual patient immune profiles or phenotypes, moving beyond trial-and-error approaches toward precision medicine. For the 10% to 15% of patients with most severe disease who remain refractory to current therapies, customized antibody approaches targeting their specific immune abnormalities represent hope for future breakthrough treatments.