New Drug
Lauren Howell, PharmD
In June 2024, for the first time in over a decade, FDA approved a new drug to treat adult patients with COPD. For the more than 16 million adults living with COPD in the United States, Ohtuvayre (ensifentrine–Verona Pharma) represents a new treatment option for the disease, which has no cure.
Ohtuvayre is a phosphodiesterase 3 and phosphodiesterase 4 inhibitor. While other oral phosphodiesterase inhibitors, including theophylline and roflumilast, have been used to treat COPD in the past, Ohtuvayre is the first to be administered by inhalation.
Dosing and administration
Ohtuvayre is packaged as a 3 mg/2.5 mL inhalation suspension in unit-dose ampules. The recommended dosage is 3 mg (one ampule) inhaled twice daily using a standard jet nebulizer.
Immediately before administering the dose, the packaged foil pouch should be opened and the ampule removed and shaken vigorously. By squeezing the ampule, the suspension should be completely emptied from the ampule and placed into the nebulizer cup. A jet nebulizer with a mouthpiece and connected to an air compressor can then be used to administer the dose. The compatibility of Ohtuvayre mixed with other drugs has not been established so it should not be physically mixed with other drugs or solutions prior to administration.
Adverse reactions and warnings
Ohtuvayre is contraindicated in patients with hypersensitivity to ensifentrine or any component of the product. The most common adverse reactions—having an incidence greater than or equal to 1% and more common than placebo in clinical studies—include back pain, hypertension, UTI, and diarrhea.
Indicated as a maintenance medication for twice daily use, Ohtuvayre should not be used to treat acute symptoms of bronchospasm. If paradoxical bronchospasm occurs with use, discontinue Ohtuvayre and initiate an alternative therapy. Use caution in patients with hepatic impairment as exposure to ensifentrine increases.
An increase in psychiatric adverse events, including suicidality, were reported with use of Ohtuvayre. Before beginning treatment, the risks and benefits of treatment in patients with a history of depression or suicidal thoughts and behavior should be weighed carefully.
Clinical trials
The efficacy of Ohtuvayre was evaluated in two 24-week randomized, double-blind, placebo-controlled, parallel-group clinical trials that were sponsored by the manufacturer. A total of 1,553 adult patients with moderate to severe COPD were enrolled in the trials.
The ENHANCE-1 trial randomized 763 patients to receive 3 mg of Ohtuvayre or placebo daily. A total of 58% of the participants were male and 90% of the participants were white. Participants had a mean smoking history of 41 pack-years with 57% identifying as current smokers.
A total of 25% reported exacerbations of COPD within the 15 months prior to the study. At screening, the mean FEV1 was 52%. Additionally, 68% of the participants were taking concurrent therapy.
The ENHANCE-2 trial randomized 790 patients to receive 3 mg of Ohtuvayre or placebo twice daily. A total of 52% of the participants were female and 95% of the participants were white. Participants had a mean smoking history of 42 pack-years and 55% were current smokers. A total of 21% of participants reported exacerbations of COPD within the 15 months prior to the study. At screening, the mean FEV1 was 51% and 55% of patients were taking concurrent therapy.
In both trials, the primary endpoint was the change in FEV1 post dose at week 12. Ohtuvayre demonstrated a statistically significant improvement compared to placebo in both trials.
To study changes in health-related quality of life, the St. George’s Respiratory Questionnaire (SGRQ) was assessed in the ENHANCE-1 and ENHANCE-2 trials. The SGRQ responder rate, which was defined as an improvement in score of 4 or more, was 58.2% in the Ohtuvayre group compared to 45.9% for the placebo group in ENHANCE-1. In ENHANCE-2, the SGRQ responder rate was 45.4% for Ohtuvayre compared to 50.3% for the placebo group.
Applicability to pharmacy practice
While clinical trials included both individuals on and not on concurrent therapy for COPD, the current FDA-approved indication for Ohtuvayre does not specify where it should fall into practice. Until more data on cost and insurance coverage, as well as updated guidelines such as the Global Initiative for Chronic Obstructive Lung Disease GOLD report, are available, Ohtuvayre’s place in practice remains to be seen. ■