Insmed Discontinues Brensocatib Development in Chronic Rhinosinusitis After Phase 2b Trial Failure
核心洞察
Insmed's Phase 2b BiRCh study of brensocatib in chronic rhinosinusitis without nasal polyps (搜索) failed to meet primary and secondary efficacy endpoints across both 10 mg and 40 mg treatment arms.
The company has immediately discontinued its brensocatib development program in CRSsNP (搜索) following the negative proof-of-concept results from the 288-patient multicenter trial.
Insmed simultaneously acquired INS1148 (搜索), a Phase 2-ready monoclonal antibody targeting SCF248 (搜索) isoform, for development in interstitial lung disease (搜索) and moderate-to-severe asthma (搜索).
Insmed Incorporated announced the failure of its Phase 2b BiRCh study evaluating brensocatib in patients with chronic rhinosinusitis without nasal polyps (搜索) (CRSsNP (搜索)), leading to immediate discontinuation of the development program. The randomized, double-blind, placebo-controlled trial failed to demonstrate efficacy in either the 10 mg or 40 mg treatment arms compared to placebo.
Trial Results Show No Therapeutic Benefit
The 288-patient study, conducted across 104 global sites, measured change from baseline in the 28-day average of daily Sinus Total Symptom Score (sTSS) at Week 24 as its primary endpoint. Results showed placebo achieved a least squares mean improvement of -2.44, while brensocatib 10 mg demonstrated -2.21 and brensocatib 40 mg showed -2.33, indicating no significant therapeutic advantage for the investigational drug.
"Given that there are no animal models in this disease, the purpose of this proof-of-concept study was to determine if brensocatib could provide treatment benefit to patients with CRSsNP (搜索)," said Martina Flammer, M.D., MBA, Chief Medical Officer of Insmed. "While we are disappointed in the results, they provided us with a clear answer."
The study randomized patients 1:1:1 to receive brensocatib 10 mg (n=99), brensocatib 40 mg (n=94), or placebo (n=95) daily for 24 weeks, all in addition to daily mometasone furoate nasal spray background therapy. Secondary endpoints included changes in sinus opacification percentage, Sino-Nasal Outcome Test 22 score, modified Lund-MacKay CT score, nasal congestion scores, and peak nasal inspiratory flow measurements.
Safety Profile Remains Consistent
Despite the efficacy failure, brensocatib demonstrated a favorable safety profile consistent with previous studies. The 40 mg dose represented the highest concentration Insmed has tested to date, with no new safety signals identified across either treatment arm. Treatment-emergent adverse event rates were comparable between active treatment groups and placebo, though specific percentages were not disclosed in the announcement.
Strategic Pivot with INS1148 Acquisition
Concurrent with the brensocatib discontinuation, Insmed announced the acquisition of INS1148 (搜索), an investigational monoclonal antibody with potential first-in-class status for respiratory and immunological inflammatory diseases. The asset, formerly known as OpSCF and developed by private clinical-stage company Opsidio (搜索), targets a specific isoform of Stem Cell Factor (搜索) SCF248 (搜索).
INS1148 (搜索)'s novel mechanism of action aims to prevent inflammatory cascades downstream of c-Kit (搜索) signaling while preserving critical homeostatic and tissue healing pathways. Insmed plans to advance Phase 2 development programs for INS1148 initially in interstitial lung disease (搜索) and moderate-to-severe asthma (搜索).
"The acquisition of INS1148 (搜索) adds a clinical-stage monoclonal antibody with a novel mechanism of action to our growing pipeline," Dr. Flammer added. "We look forward to advancing this potentially first-in-class therapy in multiple serious diseases."
Clinical Development Challenges in CRSsNP
The BiRCh study failure highlights the challenges of developing therapies for chronic rhinosinusitis without nasal polyps (搜索), a condition lacking established animal models for preclinical validation. The proof-of-concept approach was designed to determine whether brensocatib's mechanism could provide clinical benefit in this patient population, but the negative results provide definitive guidance for the program's future.
Insmed intends to present the complete BiRCh study data at a future medical congress, potentially offering additional insights into the therapeutic approach and patient population characteristics that may inform future development strategies in related inflammatory conditions.