Delving into the Latest Updates on Ensifentrine with Synapse

This study will assess the pharmacokinetics (PK), pharmacodynamics (PD) and safety of ensifentrine and glycopyrrolate fixed dose (FDC) product, the individual components of the FDC (ensifentrine and glycopyrrolate, each in the FDC formulation), ensifentrine 1.5 mg in the FDC formulation and ensifentrine 3 mg in the marketed formulation each administered via a standard jet nebulizer, in adult participants with chronic obstructive pulmonary disease (COPD).

Start Date06 Oct 2025

Sponsor / Collaborator

Verona Pharma Plc

NCT07016412

/ RecruitingPhase 2

A Phase IIb, Randomized, Double-blind, Placebo- Controlled, Parallel Group Study to Assess the Efficacy and Safety of Ensifentrine-glycopyrrolate Fixed-dose Combination at Two Dose Levels Compared to Glycopyrrolate or Ensifentrine Monotherapy in Subjects With COPD

This study will assess the safety and efficacy of fixed dose combinations of ensifentrine with two different glycopyrrolate dose levels compared to placebo and to the individual components of the fixed dose combinations, each administered twice a day via standard jet nebulizer, in adult subjects with chronic obstructive pulmonary disease (COPD).

Start Date31 Jul 2025

Sponsor / Collaborator

Verona Pharma Plc

NCT06559150

/ RecruitingPhase 2

A Phase II, Randomized, Double-Blind, Placebo- Controlled Study of Ensifentrine in Subjects With Non-Cystic Fibrosis Bronchiectasis

This study is a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of ensifentrine inhalation suspension (3 mg) delivered twice daily via standard jet nebulizer over at least 24 weeks, compared to placebo, in subjects with non-cystic fibrosis bronchiectasis (NCFBE).

Start Date11 Sep 2024

Sponsor / Collaborator

Verona Pharma Plc

100 Clinical Results associated with Ensifentrine

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100 Translational Medicine associated with Ensifentrine

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100 Patents (Medical) associated with Ensifentrine

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72

Literatures (Medical) associated with Ensifentrine

01 Mar 2026·PRESSE MEDICALE

Pharmacological management of COPD

Article

Author: Beech, Augusta ; Singh, Dave

The pharmacological management of chronic obstructive pulmonary disease (COPD) focuses on the alleviation of symptoms coupled with exacerbation prevention. Inhaled treatments are the mainstay of management, ensuring adequate lung delivery while minimising the potential for adverse systemic effects. Combination inhalers with long acting bronchodilators, with and without inhaled corticosteroids (ICS), are in widespread use to treat COPD on the basis of clinical trial evidence alongside the practical advantages associated with using a single inhaler in the real life world. There is also a personalised approach to ICS use, as blood eosinophil counts can help identify individuals with a greater probability of responding to treatment. Biological treatments have demonstrated positive results in COPD clinical trials, and will also be used in a precision approach in future. The positive clinical trial results for dupilumab (a monoclonal antibody directed against the shared IL-4 and IL-13 receptor) and ensifentrine (an inhibitor of phosphodiesterase 3 and 4) represent significant advances in the pharmacological management of COPD. This review describes the recent progress in COPD pharmacology, covering novel molecules, new evidence and changes in clinical practice.

01 Jan 2026·INTERNATIONAL IMMUNOPHARMACOLOGY

Anti-oxidative and anti-inflammatory effects of the phosphodiesterase 3/4 inhibitor ensifentrine

Article

Author: Lea, Simon ; Littolff, Kieran ; Li, Jian ; Vijayacumaran, Kajaluckcika ; Singh, Dave

Ensifentr ine is a dual PDE3/4 inhibitor that improves lung function and symptoms in COPD patients. Ensifentrine has anti-inflammatory effects, but these have not been studied in cells from COPD patients. Oxidative stress is increased in the lungs of COPD patients, but the potential for ensifentrine to modulate oxidative stress induced apoptosis has not been investigated. We investigated the effects of ensifentrine on inflammation and oxidative stress in cell models relevant to COPD. Peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy controls and human bronchial epithelial cells were treated with ensifentrine or a PDE4 inhibitor (roflumilast or GSK256066) or dexamethasone prior to exposure to lipopolysaccharide or T-cell receptor activation, with measurement of supernatant levels of TNFα and IFNγ, respectively. H₂O₂ induced oxidative stress was also investigated with measurements of caspase 3/7 activity, apoptosis associated gene expression, apoptosis and cell viability. Ensifentrine decreased production of TNFα and IFNγ in PBMCs from COPD patients and controls. IC₅₀ values for ensifentrine were greater than other compounds, while maximal inhibition was comparable at high concentrations. Ensifentrine reversed H₂O₂ induced caspase activity, alteration of apoptosis genes, apoptosis and cell death in both cell types, while PDE4 inhibitors had limited effects. These anti-apoptosis effects were dependent on PDE3-PKG-cGMP signalling. We report a novel mechanism of action for ensifentrine, reducing effects of oxidative stress through a PDE3 dependent mechanism. The anti-inflammatory effects of ensifentrine were lower compared to the PDE4 inhibitors tested.

01 Dec 2025·Chronic Respiratory Disease

Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies

Article

Author: Rickard, Kathleen Ann ; Dransfield, Mark ; Anzueto, Antonio ; Marchetti, Nathaniel ; Dixon, Amy L ; Reyner, Daniel ; Rheault, Tara ; Kalhan, Ravi

Background:

The efficacy and safety of ensifentrine, a novel PDE3/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens.

Objective:

This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS).

Methods:

Eligible patients had moderate to severe COPD, were aged 40–80 years, and were symptomatic at randomization. Patients were randomized 5:3, receiving twice-daily ensifentrine 3 mg or placebo via standard jet nebulizer over 24 weeks.

Results:

The pooled post-hoc analysis included 485 LAMA patients and 272 LABA + ICS patients. Ensifentrine showed lung function improvement over placebo at week 12, including average FEV1 AUC0–12 h in the LAMA (placebo-corrected least squares mean change from baseline [LSMC], 92 mL; 95% CI, 54, 131; p < 0.001) and LABA + ICS subgroups (LSMC, 74 mL; 95% CI, 27, 121; p = 0.002). Ensifentrine reduced the rate and risk of exacerbations in both LAMA (48% and 50%, respectively) and LABA + ICS (51% and 56%, respectively) subgroups. Ensifentrine-treated patients reported improvement in symptoms and quality of life over 24 weeks. The safety profile of ensifentrine in each subgroup was similar to the profile in the pooled modified intention-to-treat population.

Conclusions:

Nebulized ensifentrine offers a novel non-steroidal anti-inflammatory and bronchodilator treatment added to existing LAMA or LABA + ICS treatment options in patients with moderate to severe, symptomatic COPD.

196

News (Medical) associated with Ensifentrine

13 Jan 2026

·firstwordpharma.com

JPM26: Merck & Co. targets $70B in revenues by mid-2030s

Merck & Co.'s impending patent 'hill' from blockbuster cancer drug Keytruda (pembrolizumab) is increasingly looking summitable. Given its efforts to offset the PD-1 inhibitor's loss of exclusivity (LOE) in 2028, the pharma now sees $70 billion in commercial opportunity by mid-2030, CEO Rob Davis said at the JP Morgan Healthcare conference on Monday (see – Vital Signs: Merck & Co.'s cliff jumping raises stakes for biotech buyers)."That will be more than double what Keytruda will be at its peak sales based on consensus estimates in 2028," he said. "Importantly, that $70 billion is $20 billion more than where we were this time last year, due to what we've added through business development and our increasing confidence in some of our internal assets."10 key assetsThe company highlighted the breadth of its pipeline, including 20 growth drivers and 80 Phase III studies under way, though the majority of its $70-billion target — about 70% — is expected to come from 10 key assets with blockbuster potential. The suite includes commercial assets Winrevair (sotatercept-csrk), Ohtuvayre (ensifentrine) — gained from its $10-billion buyout of Verona Pharma in July — and Enflonsia (clesrovimab-cfor). Other programmes are enlicitide decanoate, ifinatamab deruxtecan, sacituzumab tirumotecan (sac-TMT), tulisokibart, MK-1405, MK-3000, and a weekly HIV regimen incorporating islatravir.Nearly all of the programmes are first-in-class molecules, and enlicitide and sac-TMT have received a Commissioner's National Priority Voucher. By the end of 2026, Davis expects to have clinically de-risked $35 billion of the $70 billion goal thanks to upcoming Phase III readouts, with a "big portion" materially de-risked in the next two years. Given the updated growth outlook, Davis said he was "quite confident that we will be in a position, at a minimum, to go through a very shallow period post-LOE, returning in a few years to growth. But we aspire for more. We aspire to grow through it," though he acknowledged that Merck is "not there yet."External opportunitiesSo how can Merck achieve growth while climbing its Keytruda patent hill? M&A could certainly be a key source. Davis noted that of its $70-billion goal, half of the revenues are expected to come from external opportunities, with internal projects responsible for the other half. "We've now invested over $60 billion since 2021 in business development," he said. "But importantly, we're not done. We have more to do."Merck will continue to focus on three disease areas — oncology, cardiometabolic and cardiopulmonary — and is open to clinical assets from Phase I through Phase III. Davis noted that as the LOE approaches, the pharma has been more focused on later-stage assets. And while its takeout sweet spot is in the $15-billion range, Davis said the company "has been very clear we're willing to go larger than that" — an important disclaimer as Merck is reportedly circling a potentially $20-billion takeout of cancer drug developer Revolution Medicines, though a highly anticipated JPM deal has not yet come to fruition (see – Vital Signs: The biggest buyers ahead of JPM)."If we see an opportunity that brings the science, where we see value will move, we have the capacity, I think, to do pretty much anything we would want to do," Davis concluded.

AcquisitionPhase 3Phase 1Phase 2

13 Jan 2026

·www.pharmaceutical-technology.com

JPM26: MSD homes in on derisking strategy amid Keytruda patent cliff

At the 2026 J.P Morgan Healthcare Conference, MSD’s (Merck & Co) CEO, Robert Davis, laid out the company’s plans to derisk its future sales amid the looming loss of Keytruda’s market exclusivity. Image credit: Jeenah Moon, Bloomberg via Getty Images. MSD’s CEO, Robert Davis, has laid out plans to derisk its projected revenue losses over the next five years amid Keytruda’s patent expiry, at the ongoing 2026 J.P. Morgan Healthcare Conference in San Francisco. In a presentation at the event, Davis painted a positive picture for the MSD’s near-term success, noting that the company’s plans to home in on the development of its late-stage pipeline, while adding that “value-adding transactions” could offer it a $70bn commercial growth opportunity. MSD’s strategic ploy comes amid the looming patent cliff facing its immune checkpoint inhibitor, Keytruda (pembrolizumab), which became the best-selling drug on the market in 2024 after bringing in $29.5bn for the company. While GlobalData forecasts that Keytruda sales will continue to grow for the next couple of years – making $35.5bn for the company in 2027 – global patents covering the drug’s market exclusivity are set to expire in 2028. This will likely result in significant losses for MSD, as Keytruda accounted for around 46% of the company’s sales in 2024. GlobalData predicts sales of the drug in 2031 to drop to $19bn. To offset this impact, MSD, known as Merck & Co in the US, has devised a strategy to add further value to its marketed portfolio, with the company expecting the launch of 20 new products, many of which have blockbuster potential, said Davis. Of these launches, 10 are expected to constitute 70% of the $70bn sales expectation by the mid-2030s, of which “nearly all” are first-in-class molecules. This includes the marketed pulmonary arterial hypertension (PAH) therapy Winrevair (sotatercept), as well as an inhaled chronic obstructive pulmonary disease (COPD) medication, Ohtuvayre (ensifentrine) and an infant respiratory syncytial virus (RSV) jab, Enflonsia (clesrovimab-cfor). GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Of the $70bn goal, there is a 50-50 split between internal and external medicines, according to the company. Also in this list are several late-stage pipeline products, such as oncology candidate sac-TMT (sacituzumab tirumotecan), which recently posted positive Phase III results in non-small cell lung cancer (NSCLC) alongside Keytruda. MSD previously licensed the global commercial rights to sac-TMT outside of greater China from Blackstone Life Sciences. MSD is also running 80 Phase III trials, which could see several new therapies make it to market. Of these, Davis highlighted human immunodeficiency virus (HIV) pill islatravir, which is currently being evaluated as both a pre-exposure prophylaxis (PrEP) therapy and a treatment for HIV alongside other antiretrovirals, including Gilead’s lenacapavir. According to Davius, islatravir could become an “anchor medicine” in the indication. GlobalData, parent company of Clinical Trials Arena , forecasts that islatravir plus Pifeltro (doravirine) will bring in $1.7bn in sales for MSD in 2033. Davis also spoke about the broadening and diversification of MSD’s pipeline, which he believes will “drive growth” moving forward. Sign up here to receive daily updates on the latest healthcare industry trends emerging from the JP Morgan Healthcare Conference 2026. Sign up here to receive a comprehensive report after the conference.

Phase 3Clinical Result

09 Jan 2026

·endpoints.news

AirNexis gets $200M to test China-derived COPD drug to compete with Merck and GSK

Another biotech has latched onto the China-to-US model, putting money behind a China asset that will be advanced by an American startup. Palo Alto-based AirNexis Therapeutics will get $200 million from investors to advance a drug for chronic obstructive pulmonary disease from Haisco Pharmaceutical Group. The drug, AN01/HSK39004, is a dual PDE3/4 inhibitor in Phase 2 testing in China. Haisco will keep the rights there and also in Hong Kong, Macau and Taiwan. It could compete against similar drugs at Merck and GSK in the disease. The investment is being backed by Frazier Life Sciences, OrbiMed, Life Sciences at Goldman Sachs Alternatives, SR One, Longitude Capital and Enavate Sciences. Haisco will also get a 19.9% stake in AirNexis, and $40 million in upfront cash. AirNexis could also end up paying as much as $955 million in future milestone payments. Error: Survey not found. Leading AirNexis is CEO Maria Fardis, who joined from Lassen Therapeutics, a small biotech in the clinic for thyroid eye disease and idiopathic pulmonary fibrosis. Lassen has not issued an announcement since its $85 million Series B in December 2023. Now at AirNexis, Fardis will attempt to go up against Merck and GSK. Merck doled out $10 billion last year to get ahold of Verona Pharma and its approved COPD maintenance drug Ohtuvayre, which is also a PDE3/4 inhibitor. GSK, meanwhile, paid $500 million upfront last year as part of a sweeping deal with Hengrui Pharma that included HRS-9821, another PDE3/4 inhibitor.

Phase 2Drug ApprovalExecutive Change

100 Deals associated with Ensifentrine

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KEGG	Wiki	ATC	Drug Bank
D11743	Ensifentrine	-	DB16157

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Pulmonary Disease, Chronic Obstructive	United States	Verona Pharma, Inc.	26 Jun 2024
Pulmonary Disease, Chronic Obstructive	United States	Verona Pharma Plc	26 Jun 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-cystic fibrosis bronchiectasis	Phase 2	United States	Verona Pharma Plc	11 Sep 2024
Non-cystic fibrosis bronchiectasis	Phase 2	Italy	Verona Pharma Plc	11 Sep 2024
Non-cystic fibrosis bronchiectasis	Phase 2	Spain	Verona Pharma Plc	11 Sep 2024
Non-cystic fibrosis bronchiectasis	Phase 2	United Kingdom	Verona Pharma Plc	11 Sep 2024
COVID-19	Phase 2	United States	Verona Pharma, Inc.	04 Sep 2020
Cystic Fibrosis	Phase 2	United Kingdom	Verona Pharma Plc	08 Feb 2017
Moderate chronic obstructive pulmonary disease	Phase 2	-	Verona Pharma Plc	01 Jan 2017
Asthma chronic	Phase 2	Sweden	Verona Pharma Plc	01 Apr 2015
Asthma chronic	Phase 2	United Kingdom	Verona Pharma Plc	01 Apr 2015
Asthma	Phase 2	Netherlands	Verona Pharma Plc	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04535986 \| NCT04542057 (ENHANCE-1/2, Pubmed \| Chron Respir Dis)	Phase 3	Pulmonary Disease, Chronic Obstructive Maintenance	-	Ensifentrine 3 mg	ayaxljwhzp(diywvgueik) = xcmpvrodnc mlusxpmfgy (kjoubskddl, 54 - 131)	Positive	01 Dec 2025
				Ensifentrine (LAMA patients)	ayaxljwhzp(diywvgueik) = lxgfoalecj mlusxpmfgy (kjoubskddl, 54 - 131) View more
NCT05743075 (ENHANCE-CHINA, PRNewswire) Manual	Phase 3	Pulmonary Disease, Chronic Obstructive	526	Ensifentrine	qranaadnyw(niitschrpa) = ibkaepuzca xqyabyffyh (jhvwddbwqu ) Met View more	Positive	16 May 2025
				Placebo	-
ENHANCE program (ATS2025)	Phase 3	Maintenance	-	Ensifentrine	hegxdiaild(jhhwtlxiyt) = fusyxiqotr feitdwndgv (vvbqeiqbzu )	Positive	16 May 2025
ATS2025	Not Applicable	Pulmonary Disease, Chronic Obstructive	-	Ensifentrine	rkhgoxmziy(onubwqrylk) = mvfnwfysgt lgyttaxruy (lbhuxrmngj, 19.87 - 64.43) View more	Positive	16 May 2025
ENHANCE program (ATS2025)	Phase 3	Heart Diseases	-	Nebulized Ensifentrine 3 mg	btkkudtjnb(eorhxfpgbl) = bfmgrmtqee rkgaizjyak (gnvqaagnhc )	Positive	16 May 2025
ENHANCE trials (ATS2025)	Phase 3	Pulmonary Disease, Chronic Obstructive	-	Ensifentrine 3 mg	ukxjymhcpj(cqkohsqysl) = reduced (improved) with ensifentrine monotherapy vs placebo at Weeks 6, 12, and 24 qhstymkmwp (vgevymsuik ) View more	Positive	16 May 2025
				Placebo
ENHANCE program (ATS2025)	Phase 3	Pulmonary Disease, Chronic Obstructive	-	Ensifentrine 3 mg	cqqrwughel(vwpuuexfhr) = fxlzmnnybb wwvezpjqft (coczmppcnn ) View more	Positive	16 May 2025
				Placebo	-
ENHANCE program (ATS2025)	Phase 3	Diabetes Mellitus, Type 2 \| Pulmonary Disease, Chronic Obstructive	-	Ensifentrine 3 mg	ikbeyncbzx(fnotshvhpl) = wwvqvirieh dpwmlifudf (xvfaaubqfa, 0.2 - 2.6) View more	Positive	16 May 2025
				Placebo	ikbeyncbzx(fnotshvhpl) = goergumwkc dpwmlifudf (xvfaaubqfa, -0.6 to 1.8) View more
ENHANCE program (ATS2025)	Phase 3	Pulmonary Disease, Chronic Obstructive \| Diabetes Mellitus, Type 2	-	Ensifentrine 3 mg	okkszcdpmr(siajhgtvrp) = jjlhgeqtih ralfxcvdnu (nyxmneatpr )	Positive	16 May 2025
NCT06460493 (CTgov)	Phase 3	Pulmonary Disease, Chronic Obstructive	20	Ensifentrine	uooeizfkyd = kjzfvurcoc trwqeodlhy (hloypgywte, akrprbmowr - bndvdzmluf) View more	-	18 Apr 2025