Verona tanks after COPD drug misses phase 2 endpoint

Lungs illustration (Image: Pixabay)
Verona argued the overall chronic obstructive pulmonary disease data set is “encouraging.” (Pixabay)

A phase 2 trial of Verona Pharma’s ensifentrine has missed its primary endpoint. The dual PDE3/PDE4 inhibitor failed to beat placebo on a measure of lung function, wiping more than 30% off Verona’s share price. 

Verona went into the readout with broadly positive data from another phase 2 in chronic obstructive pulmonary disease (COPD) in the bank. However, while the earlier trial linked ensifentrine, previously known as RPL554, to significant improvements in peak forced expiratory volume in one second (FEV1), the latest trial found it was statistically no better than placebo.

Investigators enrolled 79 COPD patients and randomized them to receive ensifentrine or placebo for three days on top of Boehringer Ingelheim’s Stiolto Respimat, an inhaled long-acting muscarinic antagonist/long-acting beta2 (LAMA/LABA) agonist. About two-fifths of participants were also taking inhaled corticosteroids. 

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The trial linked the lower, 1.5 mg dose of ensifentrine to a 46 ml improvement in FEV1 over placebo but nonetheless missed its primary endpoint. 

Verona latched onto the 46 ml benefit, performance at a later time point and statistically significant improvements in residual volume to argue the overall data set is “encouraging.” Collectively, investors gave that thesis short shrift, sending Verona’s stock spiraling downward, but some observers sided with the company’s interpretation of the data.  

“We are not overly concerned by the lack of statistical significance given the small trial,” Jefferies analyst Peter Welford and colleagues wrote in a note to investors. “The incremental +46mL FEV1 benefit with 1.5mg morning dose of ensifentrine on top of double, or even triple, standard of care is promising.”

Welford’s upbeat reading of the results is underpinned by talks with COPD experts and details of the data beyond the headline endpoint miss. The analysts described the magnitude of FEV1 benefit from the LAMA/LABA therapy alone as “impressive,” leading them to conclude that it may have been hard to show additional bronchodilatory benefits. 

Based on talks with COPD experts, the Jefferies analysts think improvements in FEV1 of 40 ml or more are “clinically meaningful in patients already considered maximally bronchodilated.” When coupled with the effect of ensifentrine on residual volume and potential for its anti-inflammatory properties to drive ongoing efficacy improvements, the analysts think the data justify forging ahead with the phase 3 strategy.

Verona is aiming to be ready to enter phase 3 around the end of the year.

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