New Jersey-based biotech Insmed Inc., announced that the Phase 2b BiRCh study assessing brensocatib in chronic rhinosinusitis without nasal polyps (CRSsNP) failed to meet its primary or secondary efficacy endpoints, prompting the company to discontinue development of the asset in this indication. Brensocatib is a dipeptidyl peptidase 1 (DPP1, also known as cathepsin C) inhibitor, with DPP1 an enzyme responsible for activating neutrophil serine proteases (NSPs) during neutrophil maturation. These proteases (such as neutrophil elastase, proteinase 3, and cathepsin G) play a role in inflammation and tissue damage in chronic inflammatory diseases, especially in the lung. By inhibiting DPP1, brensocatib reduces the activation of NSPs, aiming to decrease neutrophil-driven inflammation and tissue destruction.

Brensocatib Phase 2b BiRCh results

The randomized, double-blind, placebo-controlled Phase 2b BiRCh study evaluated brensocatib at 10 mg and 40 mg once daily versus placebo in 288 patients with CRSsNP across 104 sites globally. Patients received treatment for 24 weeks on top of background mometasone furoate nasal spray. The primary endpoint was change from baseline to the 28-day average of daily Sinus Total Symptom Score (sTSS) at Week 24, with negative values indicating symptom improvement. Topline results showed no meaningful separation from placebo: • Placebo: least squares mean −2.44 • Brensocatib 10 mg: least squares mean −2.21 • Brensocatib 40 mg: least squares mean −2.33 Secondary endpoints—including imaging-based measures of sinus opacification, Sino-Nasal Outcome Test-22 scores, modified Lund–MacKay CT scores, nasal congestion, peak nasal inspiratory flow, and use of rescue therapy—were also not met. From a safety perspective, brensocatib was generally well tolerated, with no new safety signals identified, including at the 40 mg dose, the highest studied to date. Treatment-emergent adverse event rates were comparable across treatment arms, and serious adverse events were infrequent. Insmed said it has discontinued the CRSsNP program for brensocatib effective immediately and plans to present full study data at a future scientific congress.

Strategic implications for brensocatib

Brensocatib remains a key asset in Insmed’s broader portfolio. The drug won its first approval in August 2025 as a treatment for non-cystic fibrosis bronchiectasis (NCFB) in adults and pediatric patients, marketed under the trade name Brinsupri, while development is ongoing in other inflammatory and pulmonary indications. Management characterised the BiRCh study as a proof-of-concept effort in a disease area lacking robust animal models, designed to test whether inhibition of downstream inflammatory pathways could translate into clinical benefit in CRSsNP.

Pipeline expansion with INS1148 acquisition

Alongside the clinical update, Insmed announced the acquisition of INS1148, an investigational monoclonal antibody formerly known as OpSCF and developed by private biotech Opsidio. INS1148 is described as Phase 2 ready and has the potential to be a first-in-class therapy for respiratory and immunological and inflammatory diseases with high unmet need. INS1148 selectively targets the SCF248 isoform of stem cell factor, aiming to block inflammatory signalling downstream of c-Kit while preserving pathways involved in tissue homeostasis and repair. Insmed plans to initially advance INS1148 into Phase 2 studies in interstitial lung disease and moderate-to-severe asthma. The deal adds a clinical-stage biologic with a differentiated mechanism of action to Insmed’s mid-stage pipeline, reinforcing the company’s strategic focus on pulmonary and inflammatory diseases.

Outlook

The discontinuation of brensocatib in CRSsNP underscores the challenges of translating anti-inflammatory mechanisms across heterogeneous airway diseases. At the same time, the acquisition of INS1148 signals continued pipeline investment, with Insmed positioning itself around first- and best-in-class approaches in areas of persistent unmet need.