An innovative mechanism of action in COPD treatment^1,2

Ohtuvayre is a single molecule providing bronchodilation and non-steroidal anti-inflammation.^1-9

PDE3 and PDE4 enzymes are present in various cells of the lung³*:

Smooth muscle cells

Immune cells

Epithelial cells

PDE3 and PDE4

Impact secondary messengers that play key signaling roles in the lungs^3,10

*Levels of PDE3 and PDE4 enzymes vary depending on cell type: smooth muscle cells, macrophages, and lymphocytes express both, while neutrophils, eosinophils, and fibroblasts mainly express PDE4.³

Ohtuvayre should not be used to treat acute symptoms of bronchospasm.¹

Selective inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of signaling molecules, cAMP and cGMP¹

This mechanism of action produces^1-9:

Bronchodilation
Anti-inflammation through decreased inflammatory cell recruitment and infiltration into the lung

Ohtuvayre should not be used to treat acute symptoms of bronchospasm.

*Levels of PDE3 and PDE4 enzymes vary depending on cell type: smooth muscle cells, macrophages, and lymphocytes express both, while neutrophils, eosinophils, and fibroblasts mainly express PDE4.³

Ohtuvayre should not be used to treat acute symptoms of bronchospasm.¹

cAMP = cyclic adenosine monophosphate;
cGMP = cyclic guanosine monophosphate;
PDE3 = phosphodiesterase 3;
PDE4 = phosphodiesterase 4.

For the maintenance
treatment of COPD

A first-in-class and truly novel way to improve lung function in patients with symptomatic COPD^1,2

See study results for Ohtuvayre.

Take a look at the safety profile of Ohtuvayre.

Warnings and Precautions:

Acute Episodes of Bronchospasm Ohtuvayre should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting bronchodilator.

Paradoxical Bronchospasm As with other inhaled medicines, Ohtuvayre may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with Ohtuvayre, it should be treated immediately with an inhaled, short-acting bronchodilator. Ohtuvayre should be discontinued immediately and alternative therapy should be instituted.

Psychiatric Events Including Suicidality Before initiating treatment with Ohtuvayre, healthcare providers should carefully weigh the risk and benefits of treatment with Ohtuvayre in patients with a history of depression and/or suicidal thoughts or behavior. Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts, or other mood changes, and if such changes occur to contact their healthcare provider. Healthcare providers should carefully evaluate the risks and benefits of continuing treatment with Ohtuvayre if such events occur.

Treatment with Ohtuvayre is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received Ohtuvayre (1 suicide attempt and 1 suicide). Additionally, the most commonly reported psychiatric adverse reactions in the pooled 24-week safety population were insomnia (6 patients [0.6%] Ohtuvayre 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] Ohtuvayre 3 mg; 1 patient [0.2%] placebo). Depression-related reactions including depression, major depression, and adjustment disorder with depressed mood occurred in 4 patients [0.4%] receiving Ohtuvayre and no patients receiving placebo.

Adverse Reactions: The most common adverse reactions ≥1% in Ohtuvayre and greater than placebo in the pooled population were back pain 1.8%, hypertension 1.7%, urinary tract infection 1.3%, and diarrhea 1.0%.

These are not all of the possible risks associated with Ohtuvayre. Please see Full Prescribing Information for Ohtuvayre.

To report suspected adverse reactions, contact Verona Pharma, Inc. at
1-888-672-0371 or FDA at
1-800-FDA-1088 or
www.fda.gov/medwatch.

References:
1. Ohtuvayre™ (ensifentrine). Prescribing Information. Raleigh, NC: Verona Pharma plc; 2024. 2. Anzueto A, Barjaktarevic IZ, Siler TM, et al. Ensifentrine, a novel phosphodiesterase 3 and 4 inhibitor for the treatment of chronic obstructive pulmonary disease: randomized, double-blind, placebo-controlled, multicenter phase III trials (the ENHANCE Trials). Am J Respir Crit Care Med. 2023;208(4):406-416. 3. Cazzola M, Hanania NA, Page CP, Matera MG. Novel anti-inflammatory approaches to COPD. Int J Chron Obstruct Pulmon Dis. 2023;18:1333-1352. 4. Singh D, Abbot-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018;52:1801074. 5. Singh D, Martinez FJ, Watz H, Bengtsson H, Maurer BT. A dose-ranging study of the inhaled dual phosphodiesterase 3 and 4 inhibitor ensifentrine in COPD. Respir Res. 2020;21:47. 6. Ferguson GT, Kerwin EM, Rheault T, Bengtsson T, Rickard K. A Dose-Ranging Study of the Novel Inhaled Dual PDE 3 and 4 Inhibitor Ensifentrine in Patients with COPD Receiving Maintenance Tiotropium Therapy. Int J Chron Obstruct Pulmon Dis. 2021;16:1137-1148. 7. Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP. The Pharmacology of Two Novel Long-Acting Phosphodiesterase 3/4 Inhibitors, RPL554 [9,10-Dimethoxy-2(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-Dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]. J Pharmacol Exp Ther. 2006;318(2):840-848. 8. Franciosi LG, Diamont Z, Banner KH, et al. Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials. Lancet Respir Med. 2013;1(9):714-727. 9. Rheault T, Macdonald-Berko M. Antiinflammatory pharmacology of ensifentrine. Presented virtually at: CHEST Annual Meeting; October 18-21, 2020. 10. Zuo H, Cattani-Cavalieri I, Musheshe N, Nikolaev VO, Schmidt M. Phosphodiesterases as therapeutic targets for respiratory diseases. Pharmacol Ther. 2019;197:225-242.

An innovative mechanism of action in COPD treatment^1,2

PDE3 and PDE4 enzymes are present in various cells of the lung³*:

PDE3 and PDE4

Selective inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of signaling molecules, cAMP and cGMP¹

This mechanism of action produces^1-9:

For the maintenance
treatment of COPD

A first-in-class and truly novel way to improve lung function in patients with symptomatic COPD^1,2

Indication and Important Safety
Information

Indication

Important Safety Information

Indication and Important Safety Information

Indication

Important Safety Information

An innovative mechanism of action in COPD treatment1,2

PDE3 and PDE4 enzymes are present in various cells of the lung3*:

PDE3 and PDE4

Selective inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of signaling molecules, cAMP and cGMP1

This mechanism of action produces1-9:

For the maintenance treatment of COPD

A first-in-class and truly novel way to improve lung function in patients with symptomatic COPD1,2

Indication and Important Safety Information

Indication

Important Safety Information

Indication and Important Safety Information

Indication

Important Safety Information

An innovative mechanism of action in COPD treatment^1,2

PDE3 and PDE4 enzymes are present in various cells of the lung³*:

Selective inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of signaling molecules, cAMP and cGMP¹

This mechanism of action produces^1-9:

For the maintenance
treatment of COPD

A first-in-class and truly novel way to improve lung function in patients with symptomatic COPD^1,2

Indication and Important Safety
Information