Verona Foresees FDA End-Of-Phase II COPD Meeting
Talks Will Discuss Pivotal COPD Trials For Ensifentrine
Executive Summary
Verona CEO tells Scrip Phase III COPD studies for its lead asset will start next year, take up to two years to complete, leading to commercial launch “probably in 2024.”
Verona Pharma PLC hopes to have an end-of-Phase II meeting with the FDA in the first half of 2020 to discuss the performance of its lead asset ensifentrine, and then initiate pivotal Phase III studies in the second half, its CEO, Jan-Anders Karlsson, told Scrip.
Verona develops drugs for treating chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis. The company, which is listed in both the UK and the US, does not have any commercialized products and its pipeline consists solely of ensifentrine, a first-in-class investigational dual inhibitor of two enzymes - phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4).
Ensifentrine Explained
Ensifentrine’s dual mechanism of action is unlike any other type of drug currently available or in development for respiratory diseases, according to Karlsson.
“This dual inhibition enables ensifentrine to combine bronchodilator and anti-inflammatory properties in one compound, differentiating it from existing drug classes used to treat COPD, including corticosteroids, beta2-agonists and anti-muscarinics, and we think that gives us very attractive properties for patients with respiratory diseases,” he said in an interview.
By combining bronchodilator and anti-inflammatory properties in one compound, ensifentrine also activates cystic fibrosis transmembrane conductance regulator (CFTR), the protein that is defective in cystic fibrosis. Activating CFTR helps reduce mucous viscosity and improves mucociliary clearance.
“By acting as an inhaled, dual inhibitor of PDE3 and PDE4 and stimulating the CFTR, we believe that ensifentrine has the potential to be a more effective and better tolerated treatment of COPD than existing standalone PDE4 inhibitors. We also believe these properties give ensifentrine broad potential applicability in the treatment of other respiratory diseases, including CF,” Karlsson said.
Three formulations of ensifentrine are under development for the treatment of COPD: the nebulized version of ensifentrine currently in Phase IIb clinical development for the maintenance treatment of COPD and which is planned to enter Phase III trials for this indication in 2020; a dry powder inhaler (DPI) formulation that reported positive Phase II data in August 2019; and a pressurized metered-dose inhaler (pMDI) formulation now in Phase II single dose trialing, with final data from that expected in the first quarter of 2020.
Verona may also develop ensifentrine for the treatment of cystic fibrosis and asthma, Karlsson said.
“We’ve had many studies with ensifentrine completed in asthmatics, in healthy subjects and COPD patients and we believe that the COPD patients who are currently receiving maximum available treatment are still deteriorating and would greatly benefit from ensifentrine because the mechanism is different and we know it can be added on safely to other treatments and we believe the properties – the bronchodilation and anti-inflammatory – would bring substantial symptom and quality of life improvements,” Karlsson said.
In October Verona completed enrollment in the final four-week Phase IIb study for ensifentrine as add-on to inhaled Spiriva (tiotropium bromide), a long-acting anti-muscarinic (LAMA) dry powder inhaler from Boehringer Ingelheim commonly used to treat patients with COPD and expects to report top-line results from this study by year-end or early in 2020. The Phase IIb study is designed to investigate the dose response of nebulized ensifentrine in moderate-to-severe COPD patients who are symptomatic despite treatment with Spiriva.
The goal of the study is to support optimal dose selection for the global Phase III studies which Verona hopes to start in the second 2020, comprising two trials of six-month duration, one with a six-month safety extension, in COPD patients.
“We look forward to an End-of-Phase II meeting with the FDA in the first half of 2020 when I expect we’ll have robust discussions on how best to proceed with ensifentrine,” the Swedish CEO said.
The Phase III COPD trial design should be similar to the underlying Phase II studies, with improvement in lung function, as measured by forced expiratory volume in one second (FEV1), to be an important endpoint for an eventual label,” Karlsson said.
“We have a strategy we believe that will give us a broad label so that on one day you can use it both in severe COPD patients but also in the more moderate-to-severe patients, and we will conduct separate studies to really profile ensifentrine, so that the patients who are the most severe – and their physicians – understand that this is a treatment they can use when they have no other options,” Karlsson explained.
“Completing that Phase III package will take up to two years, bringing us, if all goes to plan, to a filing for ensifentrine in 2023, with a commercial launch probably in 2024.”
Partnering Prospects
He said Verona is open to partnering ensifentrine with a well-funded pharma player for the dry powder inhaler formulation currently in Phase II
“While our focus is currently very much on nebulized ensifentrine, the machine that patients use, we are also working on a dry powder inhaler, or DPI formulation that reported very positive Phase II data in August with strong effect and good duration for twice a-day use. But that product would be for a much broader population and would need a partnership, as would a pressurized metered-dose inhaler formulation. We’d like to find a partner that would take one or the other and have the adequate resources to do so,” Verona’s CEO said.
“For us, the United States is very much nebulizer focused, with between 20 million to 30 million and nebulized treatment is reimbursed. China is also a fantastic prospect because there you have 100 million COPD patients and 90% of all prescriptions are made in hospital,” he explained.
“Europe is different. The MDI dry powder is preferred there. But patients with severe COPD cannot inhale and so cannot take treatment in that form. It’s an uphill battle in Europe and we’d therefore need a partner for that region,” he explained.
Current Financial Runway Extends To Q3 2020
The biotech’s finances give it a clear project runway into the third quarter of 2020.
“We have $50m on the balance sheet are funded up to entering Phase III studies, at which point we will need to look at additional ways to raise funds before moving to regulatory filing and approval,” Karlson said.
“That could involve the issuance of new shares to raise money, or via structured finance deals or by partnering. But we will need more funding and we want everything committed before we start the Phase III studies,” he concluded.