Verona Pharma (LSE:VRP) has come through one of the last major barriers between it and the start of a Phase IIb trial of its chronic obstructive pulmonary disease (COPD) drug. The news means that, after years of largely unsuccessful R&D into phosphodiesterase (PDE) inhibitors, another company is nearly ready to test a product from the class in a late-phase trial.Verona CEO Jan-Anders Karlsson
London-based Verona talked up the prospects for its PDE3/PDE4 inhibitor RPL554 after posting data from the final part of a Phase I/IIa trial. The trial was looking at a new suspension formulation of RPL554, a drug co-invented by revered Glaxo researcher Sir David Jack. Verona came up with the formulation, which consists of suspended particles delivered via a nebulizer, to address stability issues that made an earlier version commercially unviable. Now, Verona has data to show the safety of the new version is comparable to the old formulation and encouraging signs of efficacy.
Given the track record of PDE inhibitors, the safety data are a boost for Verona. "These compounds have a long history of rather problematic developments," Verona CEO Jan-Anders Karlsson told FierceBiotech. "What is significant is that we could go up to a very high dose, much higher than the effective dose that we used with the old formulation, and still found that the compound is well tolerated and does not show any typical PDE4-like side effects." Other PDE4 inhibitors have been blighted by their tendency to cause nausea and vomiting.
With its PDE3/PDE4 inhibitor seemingly free from these issues and offering a mix of bronchodilation and anti-inflammatory effects--in the Phase I/IIa trial forced expiratory volume increased more than 200 ml over the placebo--Karlsson sees it becoming a rare step forward in COPD care. Verona is now focused on what it sees as the shortest path to market for RPL554. The plan is to develop RPL554 as an add-on therapy for acute exacerbations in COPD patients, a process that will entail committing cash to preparations for a Phase IIb trial.
"We have funding to take us into Phase IIb," Karlsson said. That money will fund an ongoing Phase IIa dose-response study in asthmatics and a soon-to-start trial to investigate the safety of RPL554 when combined with bronchodilators. Karlsson expects to have all the data needed to enter Phase IIb by the middle of next year, at which time the pressure to locate funding will increase. "Sometime during the Phase IIb, or perhaps earlier, of course we will either partner or will find grant money or we will have some equity issue," he said.
Shares in Verona closed up more than 10% in London on the day the Phase I/IIa data was released. Even after the jump, Verona's stock is still well short of the heights it hit in 2009 on the strength of data on RPL554 in patients with asthma. Back then, RPL554 had just come through a Phase I/IIa trial in people with asthma and Verona was pushing hard to bring a partner on board. That never panned out, but now, with Phase IIb looming into view, Verona may finally get a shot at seeing if RPL554 can live up to its expectations.
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