Phase IIa trial showed significantly improved peak lung function when RPL 554 was added to tiotropium in patients with moderate-to-severe COPD.- Verona Pharma

Verona Pharma plc announced positive top-line results from its Phase IIa clinical trial, in which RPL 554 was dosed in addition to tiotropium (Spiriva), one of the most commonly used drugs to treat chronic obstructive pulmonary disease (COPD). In summary, despite the limited number of patients, the data from this Phase IIa trial demonstrated significantly improved peak lung function when RPL 554 was added to tiotropium in patients with moderate-to-severe COPD.

This was a double blind, placebo-controlled, three way cross-over trial in 30 subjects with COPD and included two different doses of RPL 554, 1.5 mg and 6 mg, or placebo, dosed twice-daily for three days, in addition to tiotropium, a long-acting anti-muscarinic (LAMA) bronchodilator, dosed once daily (ClinicalTrials.gov Identifier: NCT03028142). The primary outcome measures for the trial were peak forced expired volume in one second (FEV1) on the third day of dosing and the average FEV1 on the third day of dosing, representing measures of lung function and duration of effect. A number of secondary outcome measures were also recorded.

Of note, the 6 mg dose of RPL 554 achieved statistical significance, compared to placebo, on all primary and secondary outcome measures. The data confirmed dose dependency between the two RPL 554 doses.

Highlights: � Primary outcome measures 1 : RPL 554, compared to placebo, produced a statistically significant (1.5 mg, p=0.002; 6 mg, p<0.001) and a clinically meaningful greater than 100 ml peak fev1 on the third day of dosing additional bronchodilation when administered on top of the standard bronchodilator tiotropium spiriva. average fev1 on the third day of dosing 0 - 12 hours of rpl 554 when added on top of tiotropium was larger than that of tiotropium alone 1.5mg p="0.099;" 6 mg p><0.001). secondary outcome measures: both doses of rpl 554 produced a statistically significant faster onset of action 1.5 mg 4.2 min 6 mg 4.6 min when added to tiotropium compared to tiotropium alone 37.6 min p><0.001).the administration of rpl 554 as an add-on treatment to tiotropium caused a marked reduction in functional residual capacity 1.5 mg p><0.01; 6 mg p><0.05) and in residual volume 1.5 mg p="0.07;" 6 mg p><0.01), both measures of trapped air in the lung as compared to tiotropium alone - suggesting that rpl 554 treatment may reduce dyspnea a major debilitating symptom of copd. both doses of rpl 554 were well tolerated as add-on treatments to tiotropium. adverse reactions were consistent with previous studies with rpl 554 and tiotropium. no cardiovascular-related or gastrointestinal related adverse reactions were reported.>

Comment:Verona has designed RPL 554 to provide bronchodilation and anti-inflammatory effects without the nausea and vomiting associated with earlier PD4 inhibitors. The hope is these characteristics will complement LAMAs and improve outcomes in patients taking the widely used class of medicines.

Comment: Both RPL 554 doses were superior to placebo in terms of peak forced expired volume in 1 second (FEV1) after the third morning dose. Only the higher 6 mg dose improved on the average FEV1 achieved by placebo patients.