A combination of Verona Pharma’s COPD therapy candidate RPL554 and Spiriva (tiotropium) significantly improved patients’ lung function and appeared to ease their breathing difficulties, Phase 2a clinical trial results showed.
The double-blind, placebo-controlled study (NCT03028142) looked at the combo’s ability to benefit 30 people with chronic obstructive pulmonary disease. Patients received two doses of RPL554 and Spiriva or a placebo and Spiriva two times a day for three days. Some RPL554 patients received doses four times larger than others.
One of the most common COPD treatments, Spiriva is a long-lasting, anti-muscarinic (LAMA) bronchodilator, or substance that widens airways. It is made jointly by Boehringer Ingelheim Pharmaceuticals and Pfizer.
RPL554 is both a bronchodilator, or substance that widens airways, and an anti-inflammatory. It works by inhibiting the enzymes phosphodiesterase 3 and 4 (PDE3 and PDE4), which are associated with the development of COPD.
Clinical trials that Verona conducted before the Phase 2a study showed that a combination of RPL554 and either of two bronchodilators led to significant improvements in COPD patients’ lung function, when compared with a placebo.
The yardstick that researchers used to measure both lung function and how long the combo worked during the Phase 2a trial was peak forced expired volume in one second, or FEV1. The team measured it on the third day and averaged it for the entire treatment period. FEV1 is the amount of air a person can force from their lungs in one second.
Patients’ response to the combo was dose-related. Those on the higher RPL554 dose responded better.
In addition to improving lung function, the RPL554-Spiriva combo worked faster than Spiriva alone, researchers said.
“Top-line results from this Phase 2a study demonstrate the very significant improvement in lung function that can be achieved in COPD patients using RPL554 in addition to tiotropium, the most widely used LAMA treatment,” Dave Singh, the principal investigator of the trial, said in a press release. ‘These encouraging results reinforce the potential for RPL554 to provide a meaningful difference in the treatment of COPD patients.
The combo also appeared to reduce dyspnea, or difficulty breathing, one of the most debilitating symptoms of the disease.
Those taking RPL554 tolerated it well, and researchers found no significant adverse reactions.
“These findings extend our previous data and show that RPL554 has the potential to further improve lung function when administered as an add-on treatment to both short-acting and long-acting bronchodilators,” said Jan-Anders Karlsson, the chief executive officer of Verona Pharma.
“We continue to enroll patients in our Phase 2b study to assess nebulized [mist-formulation] RPL554 for the maintenance treatment of COPD,” he said, adding that “the data from the current study further affirms our belief that RPL554 can become a valuable addition to drugs commonly used by patients with COPD.”