Ohtuvayre From Verona Pharma

The FDA has approved ensifentrine oral inhalation suspension (Ohtuvayre; Verona Pharma) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults.¹ Approximately half of patients with COPD experience symptoms nearly every day, such as frequent coughing, shortness of breath, tightness in the chest, unusual tiredness, and wheezing. More than 8.6 million individuals in the US receive chronic treatment for COPD. Globally, the condition affects approximately 390 million people and is the third leading cause of death.²

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PHARMACOLOGY AND PHARMACOKINETICS

Ensifentrine is a phosphodiesterase-3 and phosphodiesterase-4 inhibitor, which results in increased intracellular levels of cyclic adenosine monophosphate and/or cyclic guanosine monophosphate, leading to various downstream signaling effects. Steady state is achieved by the third day of twice-daily dosing and maximum plasma concentrations are observed 0.6 to 1.5 hours after administration. Ensifentrine displays a terminal elimination half-life of 10.6 to 12.6 hours. It is metabolized primarily by CYP2C9 and to a lesser extent by CYP2D6.¹

DOSAGE AND ADMINISTRATION

The recommended dose of ensifentrine is 3 mg twice daily by oral inhalation using a standard jet nebulizer with a mouthpiece. Because the physical compatibility of ensifentrine with other medications has not been established, it should not be physically mixed with other drugs or added to solutions that contain other medications. Ensifentrine is supplied as an inhalation suspension containing 3 mg/2.5 mL (1.2 mg/mL) in unit-dose ampules.¹

CLINICAL TRIALS

The efficacy of ensifentrine was evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials, which are double-blind, parallel-group, placebo-controlled, randomized trials of adults with moderate to severe COPD. Both trials randomly assigned treatments 5:3 to either ensifentrine 3 mg by oral inhalation via standard jet nebulizer twice daily or placebo. Concurrent background therapy was allowed for the duration of the trials. In ENHANCE-1, 30% of participants used longacting muscarinic antagonists (LAMAs), 18% used long-acting ß agonists (LABAs), and 20% used LABA/inhaled corticosteroids (ICSs). In ENHANCE-2, 33% of participants used LAMAs, 7% used LABAs, and 15% used LABA/ICSs.1,2

The primary end point for both ENHANCE-1 and ENHANCE-2 was the change from baseline in the average forced expiratory volume in 1 second area under the curve (FEV1 AUC0-12h) post dose at week 12. In both trials, ensifentrine demonstrated a statistically significant improvement in FEV1 AUC0-12h compared with placebo.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with ensifentrine is contraindicated in patients with hypersensitivity to the medication or any of its components. Ensifentrine should not be used as a rescue therapy to treat acute symptoms of bronchospasm. Acute symptoms should be treated with an inhaled short-acting bronchodilator. Ensifentrine may cause paradoxical bronchospasm, which can be life-threatening. If paradoxical bronchospasm occurs, an inhaled short-acting bronchodilator should be administered immediately, ensifentrine should be discontinued, and an alternate treatment should be initiated. The use of ensifentrine is associated with increased psychiatric adverse reactions, including suicidality. The benefits and risks of treatment with ensifentrine should be carefully assessed in patients with a history of depression and/or suicidal thoughts or behavior.^1,2

There are no data regarding the use of ensifentrine during pregnancy or lactation. Its efficacy and safety in pediatric patients have not been established. The systemic exposure of ensifentrine is increased in patients with moderate or severe hepatic impairment and it should be used cautiously in this population. No dose adjustment is required in patients with mild or moderate renal impairment. The use of ensifentrine in patients with severe renal impairment has not been studied. The most common adverse reactions are back pain, diarrhea, hypertension, and urinary tract infection.¹

REFERENCES

1. Ohtuvayre. Prescribing information. Verona Pharma, Inc; 2024. Accessed August 26, 2024. https://ohtuvayrehcp.com/files/Ohtuvayre-US-Prescribing-Information.pdf

2. Verona Pharma announces US FDA approval of Ohtuvayre (ensifentrine). News release. Verona Pharma. June 26, 2024. Accessed August 26, 2024. https://www.veronapharma.com/news/verona-pharma-announces-us-fda-approval-of-ohtuvayre-ensifentrine/