Ohtuvayre (ensifentrine) for COPD

Last updated July 9, 2024, by Marisa Wexler, MS
Fact-checked by Marta Figueiredo, PhD

What is Ohtuvayre for COPD?

Ohtuvayre (ensifentrine) is an inhaled therapy approved in the U.S. as a maintenance treatment for adults with chronic obstructive pulmonary disease (COPD).

Sold in the U.S./most regions by Verona Pharma, the nonsteroidal medication is designed to improve lung function and ease symptoms in COPD patients.

Verona also is developing Ohtuvayre and other inhaled formulations of ensifentrine as a potential treatment for other lung diseases, including asthma and cystic fibrosis.

Therapy snapshot

How does Ohtuvayre work?

COPD is a chronic lung disorder that’s characterized by progressive airway inflammation and bronchoconstriction, or airway narrowing. It leads to symptoms such as shortness of breath, excessive mucus production, coughing, and wheezing, all of which can worsen over time.

Standard COPD treatment typically includes inhaled corticosteroids — medications that reduce inflammation, but whose long-term use is associated with serious side effects — and bronchodilators, which relax muscles in the lungs and widen the airways.

The active ingredient in Ohtuvayre, ensifentrine, is a first-in-class small molecule that’s designed to simultaneously lessen inflammation and prompt the airways to relax and widen.

The nonsteroidal therapy specifically works by blocking the activity of two lung enzymes, called phosphodiesterase 3 and 4; these are abbreviated as PDE3 and PDE4. PDE3 helps control the activity of the muscle cells that tighten to constrict the airways, while PDE4 is involved in the activation of inflammatory immune cells, as well as mucus production and clearance.

As such, the therapy is expected to improve lung function, ease symptoms, and reduce exacerbations, or periods of sudden symptom worsening, in COPD patients, while avoiding the side effects associated with standard inhaled corticosteroids.

Who can take Ohtuvayre?

Ohtuvayre was approved by the U.S. Food and Drug Administration (FDA) in June 2024 for the maintenance treatment of COPD in adults.

The decision made Ohtuvayre the first inhaled therapy with a new mechanism of action to be cleared for COPD in more than 20 years, and notably, the first to simultaneously work as a bronchodilator and a nonsteroidal anti-inflammatory agent.

Who should not take Ohtuvayere?

According to its prescribing information, Ohtuvayre should not be used by anyone with a known allergy to any of its ingredients.

The therapy should be used with caution in patients with liver problems.

How is Ohtuvayre administered in COPD?

Ohtuvayre is available in single-use ampules (small, sealed vials) containing 2.5 mL of a yellow to pale yellow solution with 3 mg of the therapy’s active ingredient. The recommended dose is one 3-mg ampule twice daily, once in the morning and once in the evening.

The medication is self-administered by inhaling it via a standard jet nebulizer — a device that vaporizes the medication into a mist to be breathed in; it’s equipped with a mouthpiece that’s connected to an air compressor.

The ampule should not be removed from its foil pouch until immediately before use. When it’s time to take the treatment, patients should remove the ampule, shake it vigorously, and then empty its contents into the nebulizer cup to take via inhalation.

Each dose should take about 5-7 minutes to administer.

Ohtuvayre should not be mixed with other drugs on the nebulizer or added to solutions that contain other medications.

Ohtuvayre in clinical trials

Ohtuvayre’s approval in the U.S. was based primarily on data from a pair of identically-designed Phase 3 clinical trials, dubbed ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057).

ENHANCE-1 and ENHANCE-2

The two global trials enrolled a total of 1,553 adults, ages 40 to 80, with symptoms of moderate to severe COPD. A total of 763 were involved in ENHANCE-1, while 790 took part in ENHANCE-2.

The participants were randomly assigned to receive twice-daily treatment with either Ohtuvayre (3mg) or a placebo via a standard jet nebulizer. Treatment was given for 24 weeks, or nearly six months, in ENHANCE-2, and for 24 or 48 weeks (about one year) in ENHANCE-1. Patients were allowed to continue stable background medication, including bronchodilators and/or inhaled corticosteroids.

In both trials, the main goal was to evaluate the effect of treatment on forced expiratory volume in one second (FEV1) — a common measure of lung function that assesses how much air someone can forcibly exhale in one second — after 12 weeks, or about three months. FEV1 was measured over 12 hours of exposure to the medication.

Both studies met their main goal, the results showed, with the therapy associated with a significantly greater increase in average FEV1 relative to the placebo: by 87 mL in ENHANCE-1 and by 94 mL in ENHANCE-2.

Ohtuvayre-treated patients in both trials also showed a significant improvement in maximum FEV1 compared with those on the placebo, as early as day 1, and at weeks 6, 12, and 24, meeting a secondary goal.

Patient-reported measures of symptom severity and life quality improved more with Ohtuvayre than with the placebo after six months in both studies, though the difference was statistically significant only in ENHANCE-1, not ENHANCE-2.

Data from the trials also indicated that Ohtuvayre reduced shortness of breath and the use of daily rescue medication as compared with the placebo. The therapy also significantly lowered annualized rates of moderate or severe COPD exacerbations by 36% to 43% after six months, and prolonged the time to a first moderate or severe exacerbation.

In addition, pooled results from both trials showed that Ohtuvayre’s benefits were broadly consistent across patient subgroups, regardless of a history of exacerbations in the 15 months before enrolling and the type of bronchodilators used.

Common side effects of Ohtuvayre

The most common side effects of Ohtuvayre in clinical trials include:

• back pain
• high blood pressure
• urinary tract infection
• diarrhea.

Bronchospasm

Ohtuvayre should not be used to treat acute COPD symptoms related to bronchospasm, a tightening of lung muscles that narrows the airways. Further, extra doses should not be used for that purpose. Patients with sudden breathing problems should be treated with an inhaled, short-acting bronchodilator.

Importantly, Ohtuvayre, like other bronchodilator treatments, can cause bronchospasm as a side effect — a condition called paradoxical bronchospasm. Individuals experiencing sudden breathing issues immediately after inhaling Ohtuvayre should be given immediate treatment with an appropriate short-acting bronchodilator. Such patients also should discontinue Ohtuvayre, and start an alternative maintenance treatment.

Mental health

Ohtuvayre may cause mental health problems, including suicidal thoughts and behaviors (suicidality). The benefits and risks of starting the therapy should be carefully considered in patients with histories of depression or suicidality.

Patients, caregivers, and family members should be aware of the risk of potential mood or behavior changes with Ohtuvayre, which may include development or worsening of suicidal thoughts, anxiety, insomnia, and/or depression. If any of these occur, the patient’s healthcare provider should be informed, and the benefits and risks of continuing treatment should be weighed carefully.

Use in pregnancy and breastfeeding

There are no data on the use of Ohtuvayre in people who are pregnant or breastfeeding, nor on the presence of the medication in human milk and its effects on milk production. In animal studies, the use of Ohtuvayre during pregnancy or lactation at doses much higher than what’s used in people did not cause any noteworthy problems in the offspring.

Patients who are pregnant or nursing, or plan to become pregnant or breastfeed, should work with their providers to carefully weigh the potential risks and benefits of using Ohtuvayre.

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