Verona Pharma’s lead investigational medicine RPL554, engineered to treat patients with chronic obstructive pulmonary disease (COPD) and other respiratory disorders, was found to have an effective therapeutic profile when administrated by inhalation to healthy volunteers.
This finding resulted from data obtained during a U.S. clinical trial that Verona is conducting to evaluate the pharmacokinetics (how the drug is processed in the body), safety and effectiveness of inhaled RPL554.
RPL554 is an investigative drug that has a dual mechanism of action, blocking the activity of two enzymes called PDE3 and PDE4. It combines anti-inflammatory and bronchodilator properties into a single compound, which makes it a distinctive alternative therapeutic option for patients who do not respond to currently available therapies.
Previous clinical trial data showed that treatment with RPL554, administrated alone or in combination with other bronchodilators, had the potential to improve lung function and trigger bronchodilatory effects in COPD patients. In addition, the investigative drug also was seen to induce an anti-inflammatory response in these patients.
Verona initiated a Phase 1 trial after the U.S. Food and Drug Administration (FDA) accepted its investigational new drug application in June 2017. The two-way crossover trial evaluated the inhaled drug’s response in the body – how it is absorbed, distributed, metabolized, and excreted – in 12 healthy volunteers.
The company announced it is reporting top-line results from the study earlier than expected.
Data showed that 10.4 percent of an nebulized RPL554 reached the bloodstream through the GI tract, a concentration value that was sustained for about 11.9 hours. This demonstrates that upon inhalation, RPL554 has low oral bioavailability and remains primarily in the lungs without dispersing throughout the body. Its stability results support twice-daily dosing of the inhaled drug.
“These data demonstrate that inhalation of RPL554 is an appropriate route of administration for people with COPD and other respiratory diseases,” Verona’s CEO Jan-Anders Karlsson, PhD, said in a press release.
“The low oral bioavailability seen in this PK trial reinforces that the swallowed portion of the medication contributes very little to the effects of RPL554,” he added. “The inhaled portion provides novel bronchodilator and anti-inflammatory effects, and has limited systemic exposure.”
Taken together, these results confirm that the inhaled formulation of RPL554 provides optimal delivery of medication to be used in patients with respiratory illnesses, such as COPD, asthma, and cystic fibrosis.
“We believe that our ability to consistently deliver higher doses of RPL554 directly to the lungs, while at the same time having only low levels in the bloodstream, is consistent with a promising therapeutic effect, and we continue to see good tolerability of the compound across our clinical trials,” Karlsson said.