The effectiveness and value of brensocatib for the treatment of non–cystic fibrosis bronchiectasis

Non–cystic fibrosis bronchiectasis (NCFB) is a chronic lung disease that is often characterized by symptoms such as excess mucus, shortness of breath, and chronic cough.¹ These symptoms perpetuate what is called a “vicious vortex” of chronic infection, structural lung changes, inflammation, and mucociliary clearance deterioration.^2,3 An acute worsening of these symptoms is described as a pulmonary exacerbation, which is routinely treated with antibiotics and sometimes hospitalization.¹

There are an estimated 350,000 to 500,000 adults in the United States with NCFB. However, prevalence estimates are highly dependent on the frequency and timing of high-resolution computed tomography scans, and many cases of NCFB are often underrecognized and underdiagnosed.⁴ The annual cost of care is estimated to exceed $14 billion per year in the United States, with $2 billion attributed to hospitalization.⁵ Although many cases of NCFB are considered to have no identifiable cause, a few key risk markers for prognosis include prior hospitalization and exacerbation, severity of shortness of breath, colonization with bacteria (eg, Pseudomonas aeruginosa [PsA] and nontuberculous mycobacteria [NTM]), and a lower forced expiratory volume in the first second of expiration (FEV₁).⁶

Regular airway clearance therapy, including saline nebulizers, high-frequency chest wall oscillators, and chest physical and percussion therapy, is recommended for patients with stable symptoms. These treatments present a high burden, often consuming many hours each day. Long-term inhaled and oral antibiotics are recommended for people with 3 or more exacerbations per year. However, long-term antibiotic use can lead to side effects and antimicrobial resistance. For people with substantial shortness of breath, pulmonary rehabilitation is recommended. There are no current US clinical guidelines, and guidelines outside the United States rely on low-quality evidence.⁷ Given high symptom burden and a lack of evidence, there is great unmet need for people living with NCFB.

Brensocatib (Brinsupri, Insmed, Inc.), a daily oral tablet, is a dipeptidyl peptidase 1 inhibitor that works by reducing neutrophil signaling and may reduce inflammation. Brensocatib was approved by the US Food and Drug Administration (FDA) on August 12, 2025, for the treatment of NCFB in adolescents and adults aged 12 years and older.⁸ It is the first disease-specific treatment approved for NCFB.

The Institute for Clinical and Economic Review (ICER) conducted a systematic literature review and cost-effectiveness analysis to evaluate the clinical and economic impact of brensocatib for the treatment of NCFB. This report summarizes the findings and highlights the key policy recommendations discussed at the California Technology Assessment Forum (CTAF) public meeting on September 25, 2025. The detailed report is available at https://icer.org/assessment/ncfb-2025/.

Summary of Findings

CLINICAL EFFECTIVENESS

Evidence informing the clinical effectiveness review was primary derived from the phase 3 ASPEN trial.⁹ This was supplemented by data from the phase 2 WILLOW trial.¹⁰ ASPEN was a 52-week, multicountry randomized trial that evaluated 2 doses of brensocatib (10 mg and 25 mg) vs placebo. The trial enrolled 1,680 adults with a history of at least 2 pulmonary exacerbations in the 12 months prior to screening and 41 adolescents with at least 1 pulmonary exacerbation in the prior 12 months. People with a primary diagnosis of either COPD or asthma, people with bronchiectasis due to cystic fibrosis, current smokers, and those currently receiving treatment for NTM lung infection were excluded. The primary outcome of ASPEN was the annualized rate of adjudicated pulmonary exacerbations, which was defined by having 3 symptoms (ie, increased symptoms of cough, sputum volume or consistency, sputum purulence, breathlessness, fatigue, or hemoptysis) for at least 48 hours that led to treatment with systemic antibiotics. Secondary outcomes, which were hierarchically tested for significance, included time to first exacerbation, percentage of participants who remained exacerbation free, change in postbronchodilator FEV₁, rate of severe exacerbations (defined as requiring intravenous antibiotics and/or hospitalization), and symptom burden as measured by the Quality of Life-Bronchiectasis Respiratory Symptoms Score.⁹

Treatment with either dose of brensocatib led to an approximate 20% reduction in the annualized rate of pulmonary exacerbations compared with placebo at week 52 (10 mg vs placebo rate ratio [RR] = 0.79, P = 0.004; 25 mg vs placebo RR = 0.81, P = 0.005). There was also an improvement in the time to first exacerbation in participants treated with brensocatib compared with placebo (10 mg vs placebo hazard ratio [HR] = 0.81, P = 0.02; 25 mg vs placebo HR = 0.83, P = 0.04). At the end of the study period, there were more brensocatib-treated participants (49%) who remained exacerbation free compared with placebo-treated (40%) (10 mg vs placebo RR = 1.20, P = 0.02; 25 mg vs placebo RR = 1.18, P = 0.04). All 3 groups had worsening in postbronchodilator FEV₁ compared with baseline values (−62 mL in the placebo group, −50 mL in the brensocatib 10-mg group, and −24 mL in the 25-mg group). FEV₁ worsening was statistically significantly less in the brensocatib 25-mg group compared with placebo (LS mean difference = 38, P = 0.04), but not the 10-mg group compared with placebo (LS mean difference = 11, P = 0.38). There was no significant difference in the rate of severe exacerbations in the brensocatib 25-mg group compared with placebo and no statistical test performed for brensocatib 10 mg (RR for both doses = 0.74; 10 mg P value = NA, 25 mg P = 0.21). All study groups had improvements from baseline in the Quality of Life-Bronchiectasis Respiratory Symptoms Score (10 mg: +6.8, 25 mg: +8.6, placebo: +4.8); compared with placebo; however, the improvements in both brensocatib groups were modest. No statistical test was performed for this outcome for either brensocatib dose vs placebo given the prespecified hierarchical statistical testing procedure.⁹

Brensocatib was generally well tolerated with low rates of treatment-emergent adverse events and discontinuation due to adverse events across all study groups. The most commonly reported adverse events were COVID-19, nasopharyngitis, cough, and headache, There were low rates of adverse events of special interest, such as hyperkeratosis, dental events, severe infection, and pneumonia across study groups. Although there were 14 deaths during the study, no deaths were considered related to brensocatib.⁹

LIMITATIONS OF THE CLINICAL EVIDENCE

Owing to the study design, enrollment criteria, and currently available evidence from the ASPEN trial, there is uncertainty regarding how well brensocatib will work in individuals with less symptomatic/asymptomatic NCFB, more symptomatic disease (eg, people with baseline FEV₁<50% or asthma), and children and adolescents. The trial explored some of these subpopulations but was underpowered to detect significant differences. The ASPEN trial was designed to assess brensocatib as an add-on treatment to usual care. There is substantial burden associated with currently available treatment options, but it remains unclear whether brensocatib may reduce the need for airway clearance treatments and long-term antibiotics. In addition, there is also uncertainty surrounding the impact on daily symptoms such as fatigue. Given the mechanism of brensocatib and its potential impact on the inflammation portion of the vicious vortex, there is a possibility that the reduction in inflammation with brensocatib may improve other areas of the vortex and have even greater impacts on patient important outcomes than what has been observed in the currently available shorter-term data.

LONG-TERM COST-EFFECTIVENESS

We developed a decision analytic model to estimate the long-term cost-effectiveness of brensocatib plus usual care compared with usual care alone. The model was informed by the key clinical trials and relevant published economic models.^9,11–14 In alignment with the ASPEN trial, patients who had 2 exacerbations in the prior year began treatment with brensocatib or usual care. PsA and NTM are the most common chronic infections for patients with NCFB and have great impacts on quality of life and health care costs. Therefore, the model consisted of 7 Markov health states, including NCFB with and without exacerbation, combinations of chronic PsA or NTM infections with and without exacerbation, and death. Patients could transition between all health states throughout the lifetime horizon of the model.

The key model assumptions included the following: brensocatib use was in addition to usual care, the risk of exacerbation was higher in individuals with either PsA or NTM infection compared with NCFB without chronic infection, brensocatib efficacy inputs were based on the brensocatib 25-mg arm in the ASPEN trial, treatment discontinuation from adverse events were considered only in treatment cost calculations, acute medical attention for an exacerbation would not exceed 1 cycle for most patients with exacerbation, and the proportion of severe exacerbations leading to hospitalization was similar for both brensocatib and usual care (while the overall rate of exacerbations was lower with brensocatib).

The primary analysis was from a health care sector perspective with a focus on direct medical costs. A modified societal perspective analysis included patient productivity losses from absenteeism for both inpatient and outpatient visits, as well as sick leave after hospitalization. Several scenario analyses were conducted to explore the assumptions around impact on lung function, brensocatib dose, baseline exacerbation rates, accelerating exacerbation rates over time, and disease severity. Full details on ICER’s cost-effectiveness analysis are available in the Final Evidence Report: https://icer.org/assessment/ncfb-2025/.

An annual net price of $61,600 was used for brensocatib, based on a manufacturer presentation of the likely discount from the list price following FDA approval.¹⁵ Current usual care included direct costs associated with managing NCFB (eg, outpatient medications, supportive services). In order to capture a comprehensive estimate of total health care spending over the time horizon, future unrelated health care costs generated by the surviving population and end-of-life costs were included.

Treatment with brensocatib resulted in higher quality-adjusted life-years (QALYs), equal-value life-years (evLYs), and life-years compared with usual care (Table 1). The total cost of brensocatib ($1,153,000) was higher than usual care alone ($367,000), primarily driven by the cost of treatment ($813,000). Patients treated with brensocatib had fewer exacerbations than those receiving usual care alone (14.7 vs 17.7).

TABLE 1.

Results for the Base Case for Brensocatib Added on to Usual Care Compared With Usual Care

Treatment	Treatment costa	Costs, other than treatment	Total costsb	QALYs	evLYs	Life-years	Number of exacerbationsc
Brensocatib	$834,000	$319,000	$1,153,000	9.32	9.33	13.72	14.69
Usual care	$20,600	$346,000	$367,000	9.18	9.18	13.67	17.73

^a Treatment costs included brensocatib and usual care cost. Lifetime discounted costs of brensocatib accounted for $813,000 of the $834,000 treatment cost in the brensocatib + usual care strategy.

^b Total costs included treatment (brensocatib + usual care) and direct medical costs other than the treatment cost.

^c Number of exacerbations was discounted at an annual rate of 3%. The undiscounted lifetime number of exacerbations for brensocatib and usual care strategies were 20.12 and 24.27, respectively.

evLY = equal-value life-year; QALY = quality-adjusted life-year.

The incremental cost-effectiveness ratio for brensocatib 25 mg was $5,592,000 per QALY gained and $5,249,000 per evLY gained compared with usual care alone, both of which exceed commonly used thresholds for cost-effectiveness in the United States (Table 2). Results from the modified societal perspective were similar to the base-case analysis. Annual treatment with brensocatib would have to be priced between $3,100 and $3,700 to be considered cost-effective at the $100,000 and $150,000 per QALY and evLY gained thresholds.

TABLE 2.

Incremental Cost-Effectiveness Ratios for the Base Case

Treatment	Comparator	Cost per QALY gained	Cost per evLY gained	Cost per life-year gained	Cost per exacerbation avoided
Brensocatib	Usual care	$5,592,000	$5,249,000	$14,211,000	$258,000

evLY = equal-value life-year; QALY = quality-adjusted life-year.

LIMITATIONS OF THE COST-EFFECTIVENESS MODEL

Our model used clinical inputs from currently available data of brensocatib 25 mg, as this dose is anticipated to be preferred because it showed significantly less worsening in lung function. A scenario analysis was conducted using inputs for the brensocatib 10-mg arm and results were similar. There may be clinical benefits related to the underlying mechanism of brensocatib that have not been fully explored, which limit the model’s ability to project future outcomes, such as risk for exacerbations, chronic infections, and quality of life. Although not explored in the clinical trial, there are hypotheses that improvements in lung function will lead to improved patient quality of life. A scenario analysis examined the lower decrease in FEV₁ associated with brensocatib and applied these results cumulatively over time. This scenario resulted in a lifetime incremental cost-effectiveness ratio of $1,601,000 per evLY gained, which did not impact the overall conclusions on the cost-effectiveness results. There were limited data for disease progression, cost inputs, transition probabilities, and epidemiological inputs. Results from the 52-week ASPEN trial were used to estimate transition probabilities, which led to uncertainty around long-term outcome projection. Although there is variation in the care costs across the patient population, the model comprehensively captures the medical costs of care for patients with NCFB. In lieu of direct evidence for health state–specific mortality rates for NCFB, mortality rates were estimated using data from other respiratory conditions. A modified societal perspective was conducted to include indirect costs on productivity losses associated with exacerbations for both patients and caregivers. However, there were limited data on caregiver disutility or productivity losses while a patient receives usual care for managing NCFB without exacerbations. Therefore, this was not captured in the modified societal perspective. Additional scenario analyses were conducted using alternative assumptions in the model such as the impact of lifetime changes in lung function and the impact of exacerbation rates on long-term outcomes, but none of these changed the overall conclusions regarding cost-effectiveness. The results of all scenario analyses are reported in the Final Evidence Report: https://icer.org/assessment/ncfb-2025/.

POLICY DISCUSSION

The CTAF is one of the independent appraisal committees convened by ICER to engage in the public deliberation of the evidence on the clinical and cost-effectiveness of health care interventions. The CTAF is composed of medical evidence experts and includes clinicians, methodologists, and patient advocates. The ICER report on brensocatib was the subject of a CTAF meeting on September 25, 2025. Following the discussion, panel members deliberated on key questions raised by ICER’s report.

All members of the CTAF (11-0) voted that current evidence is adequate to demonstrate that the net health benefit of brensocatib plus usual care for NCFB is superior to that of usual care alone (Table 3). The CTAF also voted on benefits beyond health and special ethical priorities (Table 4) that should be considered by policymakers as they make judgments regarding the value of brensocatib. All members of the CTAF (11-0) voted that given the available evidence, there is low long-term value for money of brensocatib as add-on therapy to usual care compared with usual care alone at assumed drug pricing (Table 5).

TABLE 3.

Votes on Comparative Clinical Effectiveness Questions

Question	Yes	No
Is the current evidence adequate to demonstrate that the net health benefit of brensocatib as an add-on therapy to usual care is greater than that of usual care alone?	11	0

TABLE 4.

Votes on Benefits Beyond Health and Special Ethical Priorities

Benefits beyond health and special ethical priorities	Strongly disagree	Disagree	Neutral	Agree	Strongly agree
To help inform judgments of overall long-term value for money, please indicate your level of agreement with the following statements:
There is substantial unmet need despite currently available treatments.	0	0	0	1	10
This condition is of substantial relevance for people from a racial and ethnic group that have not been equitably served by the health care system.	0	1	8	1	1
To help inform judgments of overall long-term value for money, please indicate your level of agreement with the following statements based on the relative effects of brensocatib plus usual care vs usual care alone:
The treatment is likely to produce substantial improvement in caregivers’ quality of life and/or ability to pursue their own education, work, and family life.	0	4	4	3	0
The treatment offers a substantial opportunity to improve access to effective treatment by means of its mechanism of action or method of delivery.	0	5	4	2	0

TABLE 5.

Votes on Long-Term Value for Money

Long-term value for money	High	Intermediate	Low
Given the available evidence on comparative clinical effectiveness and incremental cost-effectiveness, and considering benefits beyond health and special ethical priorities, what is the long-term value for money of brensocatib as add-on therapy to usual care compared with usual care alone at assumed pricing?	0	0	11

Following the discussion of the evidence, a policy roundtable was convened to deliberate on how best to apply the evidence on brensocatib for the treatment of NCFB. The full set of policy recommendations can be found in the Final Evidence Report on the ICER website: https://icer.org/assessment/ncfb-2025/.

Key policy recommendations relevant to the potential introduction of brensocatib into practice are as follows:

• 1.Manufacturers should set prices that are affordable and foster access for all patients. The launch price of $88,000 and the projected discounted price are both substantially higher than a cost-effective price, which may have a deleterious effect on patient access. The manufacturer should also engage in innovative contracting arrangements that incorporate clinical outcomes.
• 2.Until more evidence is available on the impact of brensocatib on the need for chronic antibiotics, payers should not implement coverage policy with step therapy that requires trying either brensocatib or chronic antibiotics before the other.
• 3.Payers should support reimbursement for daily airway clearance therapies, which are a critical part of NCFB care. This type of care is best optimized with access to respiratory therapists and other professionals such as nurse case managers, as their role includes helping patients complete airway clearance consistently and effectively.
• 4.Payers should ensure that there is adequate coverage for intraprofessional consultation between community physicians and subspecialty NCFB experts, and direct telehealth between experts and patients to reduce barriers in access to specialty care, especially among rural, disadvantaged, and underserved populations.
• 5.All stakeholders have a responsibility to improve care delivery and improve health equity for patients with NCFB. Patients experience missed diagnoses, diagnosis delays, and suboptimal care after diagnosis. With brensocatib being the first disease-specific therapy for NCFB, there is an opportunity to prioritize NCFB care and improve health equity.

Disclosures

Ms McKenna reports grants from Arnold Ventures and grants from The Peterson Center on Healthcare during the conduct of the study; other from Abbott, other from AHIP, other from Alnylam, other from Astra Zeneca, other from Bayer Healthcare, other from Blue Shield of CA, other from Boehringer-Ingelheim, other from CRISPR Therapeutics, other from CVS, other from Express Scripts, other from GSK, other from Health Care Service Corporation, other from Humana, other from Kaiser Permanente, other from Karuna Therapeutics, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from Novo Nordisk, other from National Pharmaceutical Council, other from Otsuka, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from Sun Life Financial, other from United Healthcare, other from Alliance of Community Health Plans, other from Abbott, other from Blue Cross Blue Shield of MA, other from CALPERS, other from Chiesi USA, Inc., other from Centene Pharmacy Solutions, other from Eisai, other from Elevance Health, other from Intellia Therapeutics, other from Point 32 Health, and other from Ventegra, outside the submitted work. Dr Kim reports grants from Institute for Clinical and Economic Review during the conduct of the study; in addition, Dr Kim has a patent Copyright Material: Economic model for assessing treatment strategies for non-cystic fibrosis bronchiectasis with royalties paid to University of Illinois Chicago, Kibum Kim, and Daniel Touchette. Dr Ollendorf reports grants from Arnold Ventures and grants from The Peterson Center on Healthcare during the conduct of the study, other from Abbott, other from AHIP, other from Alnylam, other from AstraZeneca, other from Bayer Healthcare, other from Blue Shield of CA, other from Boehringer-Ingelheim, other from CRISPR Therapeutics, other from CVS, other from Express Scripts, other from GSK, other from Health Care Service Corporation, other from Humana, other from Kaiser Permanente, other from Karuna Therapeutics, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from Novo Nordisk, other from National Pharmaceutical Council, other from Otsuka, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from Sun Life Financial, other from United Healthcare, other from Gilde Healthcare, other from ISPOR, other from Alliance of Community Health Plans, other from Abbott, other from Blue Cross Blue Shield of MA, other from CALPERS, other from Chiesi USA, Inc., other from Centene Pharmacy Solutions, other from Eisai, other from Elevance Health, other from Intellia Therapeutics, other from Point 32 Health, and other from Ventegra, outside the submitted work. Dr Richardson reports grants from Arnold Ventures and grants from The Peterson Center on Healthcare during the conduct of the study; other from Abbott, other from AHIP, other from Alnylam, other from Astra Zeneca, other from Bayer Healthcare, other from Blue Shield of CA, other from Boehringer-Ingelheim, other from CRISPR Therapeutics, other from CVS, other from Express Scripts, other from GSK, other from Health Care Service Corporation, other from Humana, other from Kaiser Permanente, other from Karuna Therapeutics, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from Novo Nordisk, other from National Pharmaceutical Council, other from Otsuka, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from Sun Life Financial, other from United Healthcare, other from Alliance of Community Health Plans, other from Abbott, other from Blue Cross Blue Shield of MA, other from CALPERS, other from Chiesi USA, Inc., other from Centene Pharmacy Solutions, other from Eisai, other from Elevance Health, other from Intellia Therapeutics, other from Point 32 Health, and other from Ventegra, outside the submitted work. Dr Touchette reports grants from Institute for Clinical and Economic Review during the conduct of the study; personal fees from Astra Zeneca and personal fees from Horizon Therapeutics, outside of the submitted work; in addition, Dr Touchette has a patent Copyright Material: Economic model for assessing treatment strategies for non-cystic fibrosis bronchiectasis with royalties paid to University of Illinois Chicago, Kibum Kim, and Daniel Touchette. Dr Wasfy reports personal fees from the Institute for Clinical and Economic Review during the conduct of the study. Dr Kim has nothing to disclose.