Verona Pharma released additional results of a Phase 2 trial demonstrating that maintenance treatment with its dry powder inhaler (DPI) formulation of ensifentrine (RPL554) is safe, and significantly improves lung function in people with moderate to severe chronic obstructive pulmonary disease (COPD).
The trial met all its primary and secondary goals, showing ensifentrine led to meaningful and dose-dependent improvements in lung function while being well-tolerated. Verona says the degree and duration of ensifentrine’s activity were highly significant, and support twice-daily use in a hand-held dry powder format.
The study evaluated ensifentrine’s safety and efficacy in a two-part Phase 2 trial (NCT04027439) involving 35 patients with moderate to severe COPD. In the first part of the study, patients were treated with one of five doses of ensifentrine DPI formulation — 150 µg, 500 µg, 1,500 µg, 3,000 µg, or 6,000 µg — or a placebo.
In March 2019, Verona reported positive early efficacy and safety data from this part, which supported continuation through the second part of the study.
In part B, patients were randomized to receive one of four dose levels — 150 µg, 500 µg, 1,500 µg, or 3,000 µg — or a placebo, administered twice daily over one week. All patients received each dose and placebo over five one-week treatment periods.
The primary efficacy measure, or endpoint, was met. Compared with placebo, repeated doses of DPI ensifentrine had a significant bronchodilator effect, seen as significant increases in peak forced expiratory volume (FEV1) from study start of 102 mL for the 150-µg dose, 175 mL for the 500-µg dose, 180 mL for the 1,500-µg dose, and 260 mL for the 3000-µg dose.
“Achieving a bronchodilator response of this magnitude in COPD patients is clinically meaningful and very encouraging,” Joseph A Boscia III, MD, pulmonary physician and principal investigator at South Carolina’s Vitalink Research-Union, said in a press release.
“This highlights the potential for ensifentrine’s unique mechanism of action to provide lung function improvement, and meet the urgent clinical need for new treatments for patients with this progressive and debilitating disease,” Boscia said.
Favorable results were also demonstrated for other secondary measures of efficacy and safety. There were significant improvements in mean FEV1 over 12 hours during one week with all doses tested. The treatment was well-tolerated at all doses, showing a pattern of adverse events similar to placebo. The safety profile was comparable to that previously observed for nebulized ensifentrine.
“These very promising data with the DPI formulation support our view that ensifentrine is an effective bronchodilator in COPD patients, whether administered as a dry powder via a hand-held inhaler or as a suspension via a nebulizer. Our proof-of-concept dry powder formulation can be adapted to different DPI devices used in the market. Millions of patients prefer to use a hand-held device, and these data significantly expand ensifentrine’s commercial potential,” said Jan-Anders Karlsson, PhD, Verona’s CEO.
“We plan to complete further development and commercialization of the DPI formulation with a partner, and these clinical data strongly support this opportunity,” Karlsson added.
Verona is developing ensifentrine in other formulations as well, including a pressurized metered-dose inhaler (pMDI). Early data from single-dose studies are expected in the second half of 2019, with final multiple-dose data anticipated for the first quarter of 2020.
Data analysis of a Phase 2b trial (NCT03443414) investigating a nebulized suspension is ongoing, with more results expected by the end of this year. The company also plans to initiate Phase 3 clinical tests for this formulation in 2020.
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