Delving into the Latest Updates on Brensocatib with Synapse

Brensocatib is an oral inhibitor of dipeptidyl peptidase 1, an enzyme that activates neutrophil serine proteases. Its potential to reduce neutrophil-driven inflammation has generated interest across a range of chronic inflammatory and respiratory conditions, particularly non-cystic fibrosis (CF) bronchiectasis. As the body of evidence supporting brensocatib continues to expand, there is a clear need for a comprehensive, rigorous, and practical narrative review to consolidate current knowledge and highlight gaps for future research. The aim of this narrative review was to systematically examine and synthesize the existing literature on brensocatib, including its pharmacology, therapeutic applications, clinical trial outcomes, safety profile, and ongoing research efforts. A systematic search was performed across major databases, EMBASE, MEDLINE, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov, through April 2025. Studies involving brensocatib in preclinical or clinical contexts were thoroughly reviewed to evaluate its efficacy and safety. Data were extracted on study design, population, dosage, outcomes, adverse events (AEs), and key findings. The most extensively studied indication was non-CF bronchiectasis, where brensocatib demonstrated a reduction in exacerbation rates and neutrophil protease activity. Preliminary evidence also suggests potential applications in CF, chronic obstructive pulmonary disease, and other neutrophilic conditions. An evaluation of the safety data indicates that the AEs reported are generally mild to moderate in severity. Brensocatib demonstrates potential as a novel anti-inflammatory therapy targeting neutrophil-mediated disease mechanisms. Further research is needed to evaluate its long-term efficacy, safety across a broader population, and its role in combination therapies.

01 Aug 2025·JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Investigating the impact of dipeptidyl peptidase-1 inhibition in humans using multi-omics

Article

Author: Keir, Holly R ; Gilmour, Amy ; Pembridge, Thomas ; Long, Merete B ; Delgado, Lilia ; Gierlinski, Marek ; Sibila, Oriol ; Peh, Zhen Hui ; Stobo, Jamie ; New, Benjamin Jm ; Singanayagam, Aran ; Chalmers, James D ; Hull, Rebecca C ; Abo-Leyah, Hani ; Thompson, A A Roger ; Turton, Helena ; Giam, Yan Hui ; Condliffe, Alison M ; McIntosh, Eve ; McLaren-Neil, Fiona ; Hughes, Chloe ; Dowey, Rebecca ; Band, Margaret ; Dicker, Alison J ; Alferes de Lima Headley, Daniela ; Richardson, Hollian

BACKGROUND:

Dipeptidyl peptidase-1 (DPP-1/Cathepsin C) processes and activates neutrophil serine proteases. Brensocatib (an oral, reversible, competitive DPP-1 inhibitor) is a novel therapy for bronchiectasis previously shown to reduce sputum protease activity and prevent exacerbations. Broader effects of DPP-1 inhibition on the immune response have not been investigated.

OBJECTIVE:

This study aimed to profile the effects of DPP-1 inhibition using a secondary analysis of the STOP-COVID19 trial.

METHODS:

The STOP-COVID19 trial was a randomized placebo-controlled trial of brensocatib 25mg in patients hospitalised for severe COVID-19 in the UK. In the primary analysis Brensocatib did not improve clinical outcomes at day 29. In a pre-specified sub-study at two UK hospitals was performed to explore the effects of DPP1 inhibition in the immune response.. blood samples were obtained at baseline and days 8, 15 and 29. Analyses included peripheral blood neutrophil mass spectrometry, neutrophil functional testing, serum cytokine analysis, whole blood mRNAseq and measurement of circulating neutrophil-associated markers.

RESULTS:

161 patients were enrolled June 2020‒January 2021 (brensocatib, n=80; placebo, n=81). Neutrophil proteomics showed significant alterations in 15 proteins (FDR p<0.01) including reductions in cathepsin G and the pseudoenzyme azurocidin-1 (FDR p<0.0001) by day 29. In serum, azurocidin-1 levels, but not total elastase or proteinase 3, were significantly reduced (p<0.0001). Neutrophil surface expression of protease-cleavable C5aR1/CD88 was significantly increased by day 29 (p<0.05). There were no differences in neutrophil extracellular traps, phagocytosis, circulating immune cell proportions or gene expression between treatment groups.

CONCLUSIONS:

Brensocatib treatment in COVID-19 altered multiple neutrophil proteins including profound effects on azurocidin-1, identifying this as a key DPP-1 target and potentially highly sensitive biomarker of treatment efficacy.

01 Jun 2025·ARCHIVES OF DISEASE IN CHILDHOOD

What is brensocatib?

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61

News (Medical) associated with Brensocatib

15 Aug 2025

·www.fiercepharma.com

Fierce Pharma Asia—Padcev's new breakthrough; China Alzheimer's drug's fate; Fosun's DPP1 deal

Padcev and Keytruda's perioperative win, Chinese regulators' decision on Green Valley's Alzheimer's drug, and Fosun's DPP1 licensing deal made our news this week. The combination of Padcev and Keytruda delivered a phase 3 win in muscle-invasive bladder cancer. China did not renew the conditional approval for a controversial Alzheimer's disease drug. Fosun Pharma is out-licensing its DPP1 inhibitor for up to $645 million. And more.1. Pfizer and Astellas' Padcev, plus Keytruda, delivers 'breakthrough' win in new bladder cancer useAfter making waves in first-line metastatic bladder cancer, the combination of Pfizer and Astellas’ Padcev and Merck & Co.’s Keytruda has shown it can extend lives when used as a perioperative treatment around surgery for patients with cisplatin-ineligible muscle-invasive bladder cancer, according to a readout from the phase 3 EV-303 study, which is also known as Keynote-905.2. China did not renew approval of controversial Alzheimer's drug, regulator's records showChina’s drug regulator did not renew the conditional nod for Green Valley Pharmaceuticals’ controversial Alzheimer’s disease med sodium oligomannate (GV-971), according to public records. The move followed a protracted review that stretched past the expiration date of the drug’s existing licensure, triggering a production and marketing halt in May.3. Expedition inks $645M pact to pocket Fosun's lung disease asset in knapsackInflammatory disease startup Expedition Therapeutics is paying $17 million upfront, plus up to $628 million in potential milestones, for ex-China rights to Fosun Pharma’s DPP1 inhibitor XH-S004. The deal was inked right before the FDA approved Insmed’s brensocatib as the first DPP1 inhibitor. The approved indication for Insmed's therapy is non-cystic fibrosis bronchiectasis.4. Aurobindo acquires US drugmaker Lannett for $250M to bolster 'reshoring' effortAurobindo is paying $250 million to buy Lannett, which is known for manufacturing attention-deficit/hyperactivity disorder medicines and generic liquids. “The acquisition strengthens Aurobindo’s ability to serve the U.S. generics space and provides strategic diversification into a specialized, high-value therapeutic category,” the Indian company said in an announcement.5. HLB taps new Elevar CEO amid liver cancer setbacks, new FDA push (Korea Biomedical Review)Korea’s HLB has tapped Byan Kim as CEO of Elevar Therapeutics. Kim will continue as co-CEO of HLB Innovation and CEO of another HLB subsidiary, Verismo Therapeutics. The move comes after Elevar and Jiangsu Hengrui Pharmaceuticals’ PD-1/VEGFR combination suffered repeated FDA setbacks in liver cancer and as Elevar prepares to file an approval for lirafugratinib in FGFR2-altered cholangiocarcinoma.Other News of Note:6. RemeGen's telitacicept meets the mark in ph. 3 Sjögren's study in China7. Indian API maker Garonit Pharma plans $46.1M antiseptic product plant in New York8. Shilpa wins India approval for world's first NAFLD med, company says (Regulatory tracker)

Drug ApprovalPhase 3AcquisitionLicense out/inExecutive Change

13 Aug 2025

·www.prnewswire.com

VytlOne Announces New Partnership with Insmed

AMARILLO, Texas, Aug. 13, 2025 /PRNewswire/ -- Maxor Specialty Pharmacy, a VytlOne company, was selected by Insmed to be a limited distribution provider of Brinsupri™. Brinsupri is a dipeptidyl peptidase 1 (DPP1) inhibitor indicated for the treatment of non-cystic fibrosis bronchiectasis (NCFB) in adult and pediatric patients 12 years of age and older. Brinsupri is the latest addition to a growing number of limited distribution products available through VytlOne. "We are excited to partner with Insmed for the launch of Brinsupri, the first FDA-approved medication for the treatment of bronchiectasis," said Joel Wright, President, VytlOne Pharmacy Services. "This milestone underscores our commitment to the rare disease community, and we are honored to play a role in the improvement of the lives of our bronchiectasis patients." About VytlOne VytlOne is the nation's only independent, fully integrated total pharmacy solutions partner. A leader in rare and orphan disease management, Maxor Specialty Pharmacy (which will be re-branded as of VytlOne Specialty Pharmacy as of January 1, 2026) integrates sophisticated clinical management strategies with a personalized high-touch approach to patient engagement, and holds licenses in all 50 states, as well as accreditations from URAC, ACHC, and The Joint Commission. VytlOne supports and enables our partners to drive sustainable revenue growth while achieving optimal outcomes for their patients living with rare disease. Learn more at . SOURCE VytlOne WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug Approval

13 Aug 2025

·www.biospace.com

Insmed Wins Approval for First Bronchiectasis Drug and DPP1 Blocker

iStock, boonstudio Insmed’s Brinsupri is the first DPP1 inhibitor approved by the FDA and the first treatment for bronchiectasis to reach the market. The FDA has signed off on Insmed’s brensocatib, to be marketed as Brinsupri, for the daily treatment of non-cystic fibrosis bronchiectasis for adults and kids 12 years and up. According to Insmed’s press announcement, Brinsupri’s approval marks two milestones for the industry: it is the first FDA approval for a DPP1 inhibitor and the first treatment cleared for the chronic pulmonary disorder. “We believe today’s news sets the stage for a strong launch for Brinsupri,” analysts at Guggenheim Partners told investors in a note on Tuesday. The firm expects Brinsupri to hit some $7.3 billion in sales by 2033. Brinsupri will cost $88,000 per year, a list price that is “a little higher” than what analysts or investors were anticipating, according to Guggenheim. The total addressable patient population for the drug in the U.S. is 500,000, according to Insmed’s announcement. Guggenheim believes that this figure is “an underestimation,” the analysts wrote, explaining that the lack of an approved non-cystic fibrosis bronchiectasis (NFCB) drug “likely limited both patient disease awareness and physicians’ incentive to diagnose their patients with this disease.” Brinsupri’s approval opens up a completely new therapeutic class: DPP1 inhibitors. Expressed by neutrophils, DPP1 is an enzyme that plays a role in triggering the inflammatory response in airways. Data from the Phase III ASPEN trial, published in The New England Journal of Medicine in April, showed that Brinsupri lowered the rate of pulmonary exacerbations by around 20% versus placebo. The Phase II WILLOW trial also supported Tuesday’s approval, demonstrating a roughly 40% reduction in the risk of exacerbations relative to placebo. Given Brinsupri’s unique market niche, Insmed could, instead of partnering with a larger pharma, conceivably commercialize the asset on its own , having set launch preparations in motion in the months leading up to the approval. Last month, for instance, Insmed put some 7.81 million shares of its common stock up for sale for $96 each, expecting gross proceeds of $750 million . The company at the time explicitly noted that this money would help it with pre-launch and commercial activities for the drug. During its first-quarter earnings report , Insmed also revealed its intent to establish a secondary manufacturing source for Brinsupri. Insmed is also continuing to build out Brinsupri’s clinical pro bronchiectasis. The biotech is also testing it for hidradenitis suppurativa, an inflammatory skin condition, and chronic rhinosinusitis without nasal polyps, both of which are in mid-stage development.

Drug ApprovalPhase 3Phase 2Clinical ResultFinancial Statement

100 Deals associated with Brensocatib

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Non-cystic fibrosis bronchiectasis	United States	Insmed, Inc.	12 Aug 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bronchiectasis	NDA/BLA	European Union	Insmed, Inc.	-
Bronchiectasis	NDA/BLA	United Kingdom	Insmed, Inc.	-
COVID-19	Phase 3	United Kingdom	Insmed, Inc.	05 Jun 2020
Hidradenitis Suppurativa	Phase 2	United States	Insmed, Inc.	16 Dec 2024
Hidradenitis Suppurativa	Phase 2	Australia	Insmed, Inc.	16 Dec 2024
Hidradenitis Suppurativa	Phase 2	Bulgaria	Insmed, Inc.	16 Dec 2024
Hidradenitis Suppurativa	Phase 2	Canada	Insmed, Inc.	16 Dec 2024
Hidradenitis Suppurativa	Phase 2	France	Insmed, Inc.	16 Dec 2024
Hidradenitis Suppurativa	Phase 2	Germany	Insmed, Inc.	16 Dec 2024
Hidradenitis Suppurativa	Phase 2	Greece	Insmed, Inc.	16 Dec 2024

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Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03218917 (WILLOW, FDA_CDER) Manual	Phase 2	Non-cystic fibrosis bronchiectasis	256	BRINSUPRI 10 mg	-	Positive	12 Aug 2025
				BRINSUPRI 25 mg
NCT04594369 (ASPEN, FDA_CDER) Manual	Phase 3	Non-cystic fibrosis bronchiectasis	1,721	Placebo	ipwynhxniv(gpzleptnbd) = zbklczmuhe ictcezuucz (afvertteid ) View more	Positive	12 Aug 2025
				BRINSUPRI 10 mg	ipwynhxniv(gpzleptnbd) = oycdbktcss ictcezuucz (afvertteid ) View more
NCT04594369 (ASPEN, ATS2025)	Phase 3	Non-cystic fibrosis bronchiectasis Neutrophil serine proteases (NSPs) \| neutrophil elastase	-	Brensocatib 10mg	nsviuzjlge(ncjrtcnleq) = mnhkmaaree gkbgevvlul (tlphixyhct ) View more	Positive	16 May 2025
				Brensocatib 25mg	nsviuzjlge(ncjrtcnleq) = trerleqqaf gkbgevvlul (tlphixyhct ) View more
NCT04594369 (ASPEN, Pubmed \| N Engl J Med)	Phase 3	Bronchiectasis neutrophilic inflammation	1,721	Brensocatib 10 mg	pmpvbpengr(lsqazctfeh) = higher incidence with brensocatib nxalamgwzm (efiqlfqggz )	Positive	24 Apr 2025
				Brensocatib 25 mg
NCT04594369 (ASPEN, PRNewswire) Manual	Phase 3	Bronchiectasis	-	Brensocatib 10 mg	xaoceycqoi(embwpqkffp) = cwevwghftc jorhwdbghu (hwkvnqqqvn ) View more	Positive	08 Oct 2024
				Brensocatib 25 mg	xaoceycqoi(embwpqkffp) = rpwspcwgco jorhwdbghu (hwkvnqqqvn ) View more
NCT04594369 (ASPEN, Company_Website) Manual	Phase 3	Bronchiectasis	1,721	Brensocatib 10 mg	aurzkkoqea(bnfkhwgfnn) = mwnydwqgek jhfwgknprk (yjpwxoiwhg ) View more	Positive	28 May 2024
				Brensocatib 25 mg	aurzkkoqea(bnfkhwgfnn) = tzdfpruljy jhfwgknprk (yjpwxoiwhg ) View more
NCT05673603 (ATS2024) Manual	Phase 1	Non-cystic fibrosis bronchiectasis	28	Brensocatib (Subjects with mild renal impairment)	cucbdelwmp(qfodddugat) = There were no treatment-emergent AEs, serious AEs, or death during this study. sbfbyvdpkk (ahqcuhhuvy )	Positive	22 May 2024
				Brensocatib (Subjects with moderate renal impairment)
NCT04817332 (STOP-COVID19, CTgov)	Phase 3	COVID-19	406	Brensocatib (Brensocatib)	srnfqtbotx = gjfyazvznj nwzjakzpvq (htncwjgmfq, pplnjziyzj - yyvtoecest) View more	-	22 Aug 2023
				Placebo (Placebo)	srnfqtbotx = cwkarhphvj nwzjakzpvq (htncwjgmfq, akolxmhdoc - ppmwzjpamv) View more
ATS2023	Not Applicable	Bronchiectasis	-	Brensocatib 25mg	eatfiootkz(sweocjckqp) = pslwyjkfth usxymqrsxx (lmeptasetr )	-	21 May 2023
				Placebo	eatfiootkz(sweocjckqp) = gkbrmfjreg usxymqrsxx (lmeptasetr )
NCT03218917 (WILLOW, CTgov)	Phase 2	Non-cystic fibrosis bronchiectasis	256	Brensocatib 10 mg (Brensocatib 10 mg)	gnklsqpbax(fdizayvgyj) = xvsuknlqjw fuxinceizm (laxxxxzdle, emurtggzem - xbxjoeoazt) View more	-	08 Feb 2023
				Brensocatib 25 mg (Brensocatib 25 mg)	gnklsqpbax(fdizayvgyj) = stmshuyset fuxinceizm (laxxxxzdle, ojjqwodvww - ilaplqqvsz) View more