Verona Pharma announces next study of nebulised ensifentrine

Clinical-stage biopharmaceutical company Verona Pharma announced the initiation of a phase 2b dose-ranging study evaluating nebulised ensifentrine (RPL554) added on to a long-acting bronchodilator in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) on Tuesday.

The AIM-traded firm said it anticipated reporting data around the end of the year, and beginning phase 3 clinical trials for the indication in 2020.

It described ensifentrine as a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4, that had been shown to act both as a bronchodilator and anti-inflammatory agent in a single compound.

“In addition to further evaluating the potential of nebulized ensifentrine as a first-in-class therapy in symptomatic COPD patients already receiving a long-acting bronchodilator, this study is an important step towards optimising the clinical profile of ensifentrine for the planned end-of-phase 2 meeting with the FDA in the first half of 2020,” said Verona Pharma chief executive officer Jan-Anders Karlsson.

“The study is also expected to further inform the phase 3 clinical development program for ensifentrine in terms of dose selection, patient population, background therapy and clinical endpoints.”

The company said the four-week, randomised, double-blind, dose-ranging trial planned to enroll around 400 patients with moderate-to-severe COPD, to evaluate the safety and efficacy of nebulised ensifentrine when added on to inhaled tiotropium - a long-acting anti-muscarinic (LAMA) commonly used to treat COPD.

Patients would receive twice-daily dosing of nebulised ensifentrine for 28 days, at four dosage levels - 0.375 mg, 0.75 mg, 1.5 mg and 3.0 mg.

The trial was being performed at about 50 sites in the United States.

Verona said the primary endpoint of the trial was improvement in lung function with ensifentrine after four weeks of treatment, as measured by peak forced expiratory volume in one second (FEV1), which is a standard measure of lung function.

FEV1 would be measured from 0 to three hours after dosing.

Key additional endpoints included measurements of respiratory symptoms and quality of life measures via different patient-reported outcome tools.

The board said that in prior phase 2 clinical studies in patients with moderate to severe COPD, ensifentrine had shown “significant and clinically meaningful” improvements in both lung function and COPD symptoms, including breathlessness.

In addition, ensifentrine had further improved lung function and reduced lung volumes in patients taking standard short- and long-acting bronchodilator therapy, including maximum bronchodilator treatment with dual and triple therapy.

Ensifentrine had been “well tolerated” in clinical trials involving more than 800 people to date.

In addition to advancing the nebulised formulation of ensifentrine through phase 2b clinical development, Verona Pharma said it had also developed a dry powder inhaler and a pressurised metered dose inhaler formulation of ensifentrine.

In an ongoing phase 2 clinical trial, it said the dry powder inhaler formulation demonstrated dose-dependent, significant bronchodilation following a single dose, and was currently being evaluated over one week of twice-daily treatment, with top-line data expected in the third quarter.

The pressurised metered dose formulation, meanwhile, was planned to enter clinical evaluation in a phase 2 study in COPD patients later in the current quarter.

Company narrows losses per share in first quarter

At the same time on Tuesday, Verona Pharma also updated the market on its finances for the three months ended 31 March, reporting cash, cash equivalents and short term investments at period end of £54m, down from £64.7m on 31 December.

It said its reported operating loss totalled £7.8m for first quarter, widening from £5.9m, with its reported loss after tax narrowing to £5.4m from £15.3m year-on-year.

Operating expenses increased due to an expansion of research and development activity, the board explained.

It added that the decrease in the net loss for the three months included an amount of £1.6m within finance income, relating to a reduction in the fair value of the liability representing the outstanding warrants to purchase Verona Pharma shares.

That compared to the three months ended 31 March 2018, when the fair value of the warrants increased by £9m, which was recorded within finance expenses.

Those movements in the fair value of the warrant liability were non-cash items.

Reported losses per share totalled 5.1p for the three months ended 31 March, narrowing from 14.5p at the same time last year.

Net cash used in operating activities was £9.9m in the period, rising from £6.2m year-on-year and reflecting increased clinical activities and the timing of supplier payments.

“The phase 2b clinical trial with nebulized ensifentrine for COPD has begun as planned and we anticipate completing patient dosing in this study by the end of 2019,” said Jan-Anders Karlsson.

“We then plan to advance into our phase 3 clinical trial programme, which we expect to commence in 2020 following the completion of the end of phase 2 meeting with the FDA.

“We reported positive interim data from our first inhaler study which opens an opportunity to provide an ensifentrine inhaler to the millions of COPD patients who prefer to use a handheld inhaler device.”