Nebulizer fails PhII COPD study, but Verona plans to march on
Billed as the first new class of bronchodilator in more than four decades, Verona Pharma’s $VRNA experimental nebulizer did not confer statistically significant improvement on a measure of lung function in Phase II study involving patients with chronic obstructive pulmonary disease (COPD) who were already on inhaled long-acting bronchodilators.
Verona has touted the drug, known as ensifentrine or RPL554, as the first potential therapy for respiratory diseases that acts as both a bronchodilator and anti-inflammatory agent in a solitary compound. Two doses of the drug in a nebulized formulation were being tested in the three-day, placebo-controlled trial as a maintenance treatment for 79 COPD patients, who were already on commonly used LAMA/LABA treatments.
Patients received three days of treatment with each of two dose strengths (1.5 mg or 6 mg) of nebulized ensifentrine or placebo twice daily. The primary endpoint was improvement in lung function with ensifentrine, as measured by FEV1 (forced expiratory volume in one second), a standard measure of respiratory function, four hours post-dose after the morning dose on day three.
The primary endpoint of FEV1 was not found to be statistically significant after the morning dose, although the smaller ensifentrine dose improved peak FEV1, the company said, adding that the improvement was maintained throughout the 24-hour period on day 3. The company’s shares slumped about 36% in midday trading.
However, data on secondary endpoints including peak FEV1 over time and reductions in residual volume were encouraging: Peak FEV1 after evening dose on day 3 showed statistically significant improvement with both doses, and statistically significant reductions in mean residual volume were observed 15 minutes following the evening dose on day 3, the London-based company said.
Overall, the higher dose did not result in greater improvement in lung function as compared with the 1.5 mg dose.
But Verona struck an upbeat tone. “Having demonstrated in previous studies the potential of ensifentrine to deliver benefits to patients on no or single bronchodilator therapy, we believe that this short study continues to support our view that ensifentrine may also be of benefit to more severe COPD patients on dual and triple therapy, for whom there are few other treatment options,” said Verona chief Jan-Anders Karlsson in a statement.
“While we are disappointed that this exploratory Phase 2 study did not achieve statistical significance for its primary endpoint, these data give us clarity on the design…for future long-term studies.”
SunTrust Robinson Humphrey’s Edward Nash appeared to agree with the company’s assessment, saying that the trial’s main goal was not met due to an unexpectedly higher placebo effect – otherwise the drug did show improved FEV1 on top of dual/triple therapy in a very challenging COPD patient population.
“We believe the FDA would welcome the lower dose from a safety standpoint and believe totality of data which includes ~104mL and 127mL improvement on top of monotherapy (tiotropium) background and 40mL to 50mL FEV1 improvements seen in dual/triple background therapy reported today provides a positive clinical and commercial profile for ensifentrine.”
Of the patients treated with dual bronchodilator (LAMA/LABA) and triple therapy (LAMA/LABA/ICS), research suggests that up to 40% (approximately 800,000 patients in the US alone) are uncontrolled, remaining symptomatic and at an increased risk of exacerbations, according to Verona.
Data have suggested that ensifentrine is an effective addition to single bronchodilators. The company is currently conducting a Phase II trial to evaluate a dry powder inhaler formulation of ensifentrine for the same patient population, and plans to test ensifentrine in a metered-dose inhaler formulation in patients with COPD. In addition, the drug is also being tested for use in cystic fibrosis and asthma.