Ensifentrine, now Ohtuvayre, wins FDA approval for COPD

Inhaled maintenance therapy now OK'd for adults is nonsteroidal medication

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has approved Verona Pharma’s ensifentrine as an inhaled maintenance therapy for adults with chronic obstructive pulmonary disease (COPD).

The decision makes ensifentrine — to be marketed under the brand name Ohtuvayre — the first therapy with a new mechanism of action to win approval for COPD in more than two decades.

Importantly, the therapy is a nonsteroidal molecule with anti-inflammatory and airway-widening effects. It therefore is expected to effectively improve lung function, ease symptoms, and reduce the risk of exacerbations in COPD patients, while avoiding the side effects associated with standard inhaled corticosteroids.

“The approval of Ohtuvayre is a significant advance in COPD care, and we believe Ohtuvayre’s novel profile can change the treatment paradigm for COPD,” David Zaccardelli, president and CEO of Verona, said in a company press release.

Ohtuvayre is expected to be commercially available in the U.S. within the next few months “through an exclusive network of accredited specialty pharmacies,” Verona stated in the release.

According to Zaccardelli, the goal is to ensure that “Ohtuvayre is available to help the millions of patients who still experience daily COPD symptoms,” and the therapy’s launch is being planned for the third quarter of the year.

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Therapy prescriptions may start July 15, according to the treatment’s webpage. In parallel, the company also will launch Verona Pathway Plus, a program meant to help patients and their caregivers navigate access and resources for Ohtuvayre.

Verona did not specify the list price for the newly approved therapy. According to an analysis from the Institute for Clinical Economic Review (ICER), Ohtuvayre would meet common cost-effectiveness thresholds if its annual price is between $7,500 and $12,700. ICER is a nonprofit organization whose therapy cost-effectiveness assessments increasingly influence price negotiations and reimbursements in the U.S.

COPD is a chronic inflammatory lung condition marked by progressive airway narrowing and inflammation, making it hard to breathe. Its symptoms include shortness of breath, coughing, and wheezing, which can worsen over time.

Therapies commonly used to control COPD are inhaled corticosteroids — which 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.

COPD has a significant impact on both mortality and morbidity in the US, and until today, innovation in inhaled treatment modalities has been limited to combinations of existing treatment classes for over two decades. … Ohtuvayre … offers a needed, unique approach and is an important advance in the treatment of COPD.

The approval of Ohtuvayre, with its new mechanism of action, was welcomed by Michael Wells, MD, an associate professor in the division of pulmonary, allergy, and critical care medicine at the University of Alabama Birmingham.

“In my experience, despite maintenance therapy, most patients report grappling with daily symptoms, including breathlessness and persistent coughing,” Wells said. “COPD has a significant impact on both mortality and morbidity in the US, and until today, innovation in inhaled treatment modalities has been limited to combinations of existing treatment classes for over two decades.”

Ohtuvayre is a first-in-class small molecule that suppresses the activity of phosphodiesterase 3 and phosphodiesterase 4, two lung enzymes involved in muscle contraction and airway inflammation, as well as mucus production and clearance.

By targeting these proteins, the nonsteroidal therapy aims to simultaneously widen the airways and lessen inflammation, while also promoting mucus clearance.

“Ohtuvayre, as a first-in-class PDE3 and PDE4 inhibitor, offers a needed, unique approach and is an important advance in the treatment of COPD,” Wells said.

The therapy’s webpage states that the “new, non-steroidal COPD treatment that can offer better breathing in just two 5- to 7-minute treatments a day.”

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Approval of Ohtuvayre supported by data from 2 ENHANCE trials

Verona’s application seeking Ohtuvayre’s approval was based mainly on data from a pair of Phase 3 clinical trials called ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057).

Collectively, the ENHANCE studies involved more than 1,400 people with moderate or severe COPD. Participants were randomly assigned to take either the therapy or a placebo twice daily via a nebulizer for about six months; most participants were also taking other bronchodilators.

The trials were designed to test whether Ohtuvayre could outperform a placebo at improving forced expiratory volume in one second (FEV1), a standard assessment of lung function based on how much air someone can blow out in a single forceful breath.

The results showed that FEV1 was significantly higher with Ohtuvayre than the placebo after 12 weeks, or about three months, and the difference persisted through the end of the six-month-long studies.

Analyses also indicated that patients given Ohtuvayre were less likely to experience exacerbations, or periods of sudden symptom worsening, and that the results were consistent across multiple subgroups, including patients taking different types of bronchodilators.

Ohtuvayre was generally well tolerated in the ENHANCE studies. The most common side effects of the therapy include back pain, high blood pressure, urinary tract infection, and diarrhea.

Importantly, the therapy may increase the risk of psychiatric problems including suicidality, so its use needs to be carefully considered in patients with a history of mental illness.

Ohtuvayre’s prescribing information notes that it should not be used to treat acute symptoms of airway tightening, known as bronchospasm, and that it should be discontinued if patients experience bronchospasm after starting on the therapy.