Most HS treatments work by suppressing the inflammatory cytokines that drive the disease, primarily TNF-alpha or IL-17. Brensocatib works differently. It targets dipeptidyl peptidase 1 (DPP1), an enzyme that activates neutrophil serine proteases, a key driver of the neutrophil-mediated inflammation that contributes to HS tissue destruction. If the CEDAR Phase 2b trial results are positive, brensocatib would represent the first entirely new mechanism of action for HS in years.
What Is Brensocatib?
Brensocatib is an oral, once-daily small-molecule inhibitor of DPP1, developed by Insmed. DPP1 is an enzyme found in neutrophil precursors in the bone marrow. It activates neutrophil serine proteases (NSPs), including neutrophil elastase, proteinase 3, and cathepsin G. These NSPs are released when neutrophils are activated and contribute to tissue damage and the chronic inflammatory cycle in HS.
By inhibiting DPP1, brensocatib reduces the activation of NSPs in newly formed neutrophils, leading to a gradual reduction in NSP activity over time as older neutrophils are replaced by new ones with lower NSP levels. This is a fundamentally different approach from biologics, which block specific cytokines, or JAK inhibitors, which block intracellular signaling pathways.
The CEDAR Trial
The CEDAR study (NCT06685835) is a Phase 2b randomized controlled trial evaluating the efficacy and safety of brensocatib in adults with moderate-to-severe HS. The trial tests two doses of brensocatib (10mg and 40mg daily) against placebo. Insmed completed enrollment in October 2025, and results are expected in 2026.
Brensocatib is already approved by the FDA for bronchiectasis (a lung condition also driven by neutrophil-mediated inflammation), under the brand name Brensocatib. This existing approval provides some reassurance about the drug's safety profile, though the HS indication would require its own regulatory review.
Why Neutrophils Matter in HS
Neutrophils are the most abundant white blood cells in the body and are the first responders to infection and tissue damage. In HS, neutrophils accumulate in lesions and tunnels, releasing proteases and reactive oxygen species that damage surrounding tissue. This neutrophil-driven destruction contributes to tunnel formation, scarring, and the chronic, recurrent nature of HS.
Current biologic therapies primarily target the adaptive immune response (T-cell-driven cytokines like TNF-alpha and IL-17). Brensocatib targets the innate immune response via neutrophils, which means it could work in patients who have not responded to biologics, or could complement biologic therapy by addressing a different arm of the inflammatory response.
What to Watch For
CEDAR trial results are expected in 2026. If positive, Insmed would likely proceed to Phase 3 trials before seeking FDA approval for HS. Patients interested in participating in brensocatib research can check ClinicalTrials.gov (NCT06685835) for current trial status and enrollment information. The HS community will be watching these results closely, as a new mechanism of action would meaningfully expand treatment options, particularly for patients who have exhausted current biologic options.