Ensifentrine combines bronchodilator and anti-inflammatory properties in one compound and has the potential to be an effective treatment for COPD and other respiratory diseases, including asthma and cystic fibrosis.
Ensifentrine has been well tolerated in clinical trials involving more than 2,200 subjects. It is designed to maximize its effectiveness and reduce adverse events through:
high dual selectivity of phosphodiesterases 3 and 4 (PDE3 and PDE4) over other enzymes and receptors to minimize off-target effects;
direct delivery to the lungs by inhalation to maximize pulmonary exposure to ensifentrine while minimizing systemic distribution and potential adverse events.
Unique mechanism of action
Ensifentrine is a first-in-class, inhaled, dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes. This selective dual inhibition enables it to combine bronchodilator and anti-inflammatory properties in one compound, differentiating it from existing drug classes used to treat COPD, including corticosteroids, beta2-agonists and anti-muscarinics.
Ensifentrine also activates the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is beneficial in reducing mucous viscosity and improving mucociliary clearance. This potentially makes it an attractive therapy for the treatment of cystic fibrosis.
Ensifentrine has the potential to substantially improve both lung function and quality of life of respiratory patients who are not satisfactorily treated with available drugs.
We have evaluated nebulized ensifentrine in the Phase 3 clinical program ENHANCE (Ensifentrine as a Novel inHAled Nebulized COPD thErapy) for COPD maintenance treatment. Ensifentrine met the primary endpoint in both ENHANCE-1 and ENHANCE-2 trials demonstrating statistically significant and clinically meaningful improvements in lung function. In addition, ensifentrine significantly reduced the rate and risk of COPD exacerbations in pooled analysis from ENHANCE-1 and ENHANCE-2.
We have reported positive Phase 2 results with DPI and pMDI formulations of ensifentrine demonstrating significant improvements in lung function in COPD patients. Ensifentrine also has potential applications in cystic fibrosis, asthma and other respiratory diseases.
Indication & Formulation
This range of Verona Pharma-supported publications provide further pharmacologic background to the research that we are engaged in.
Gary T Ferguson, Edward M Kerwin, Tara Rheault, Thomas Bengtsson, Kathleen Rickard
International Journal of Chronic Obstructive Pulmonary Disease, April 22, 2021
Mark Turner, Nurlan Dauletbaev, Larry Lands and John W. Hanrahan
Journal of Pharmacology and Experimental Therapeutics, 4 October 2020
Henrik Watz, Kathleen Rickard, Tara Rheault, Thomas Bengtsson, Dave Singh
International Journal of Chronic Obstructive Pulmonary Disease, 16 September 2020
Dave Singh, Fernando J. Martinez, Henrik Watz, Thomas Bengtsson, Brian T. Maurer
Respiratory Research, 10 February 2020
Tara Rheault and Margot Macdonald-Berko
MedNous, July/August 2019
Leif Bjermer, Katharine Abbott-Banner, Kenneth Newman
Pulmonary Pharmacology & Therapeutics, 14 June 2019, 101814
David Singh, Katharine Abbot-Banner, Thomas Bergtsson, Kenneth Newman
Eur. Respir. J. 2018
Lui G Franciosi, PhD, Prof. Zuzana Diamant, MD, Katharine H Banner, PhD, Rob Zuiker, MD, Nicoletta Morelli, MD, Ingrid M C Kamerling, PhD, Marieke L de Kam, MSc, Prof. Jacobus Burggraaf, MD, Prof. Adam F Cohen, MD, Prof. Mario Cazzola, et al.
The Lancet Respiratory Medicine, October 25 2013, http://dx.doi.org/10.1016/S2213- 2600(13)70187-5
Katharine H. Abbott-Banner and Clive P. Page
Basic & Clinical Pharmacology & Toxicology Doi: 10.1111/bcpt.12209
Franciosi L, Diamant Z, Morelli N, de Kam M, Cohen A, Walker M, Page CP.
Clin Transl Allergy. 2013; 3 (Suppl 1): O13
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