Mylan: Revefenacin Meets Primary Efficacy Endpoint, Shown To Be Well-Tolerated

(RTTNews) - Theravance Biopharma Inc. and Mylan N.V. (MYL) announced positive results from two replicate Phase 3 efficacy studies of revefenacin (TD-4208), an investigational long-acting muscarinic antagonist or LAMA and the first once-daily, nebulized bronchodilator in development for the treatment of chronic obstructive pulmonary disease or COPD.

Top-line results across more than 1,250 moderate to very severe COPD patients confirmed that both Phase 3 studies met their primary efficacy endpoint, demonstrating statistically significant improvements over placebo in trough forced expiratory volume in one second (FEV1) after 12 weeks of dosing for each of the revefenacin doses studied (88 mcg once daily and 175 mcg once daily).

The trials demonstrated statistically and clinically relevant increases in trough FEV1 after 12 weeks of once-daily dosing. The improvements in trough FEV1 compared to placebo for the intent-to-treat population across both studies were 118 mL and 145 mL for 88 mcg and 175 mcg, respectively.

In pre-specified pooled analyses, revefenacin produced increases in trough FEV1 in the subgroup (38%) of patients using background long-acting beta agonist (LABA) containing therapies and in the subgroup of patients who were not using concomitant LABA therapy. The improvements in FEV1 for the LABA subgroup were 92 mL and 135 mL for 88 mcg and 175 mcg, respectively, and for the non-LABA subgroup were 131 mL and 150 mL for 88 mcg and 175 mcg, respectively.

The studies also demonstrated that the 88 mcg and 175 mcg doses of revefenacin were generally well-tolerated, with comparable rates of adverse events and serious adverse events across all treatment groups (active and placebo). The most commonly reported adverse events, across both trials and across all treatment groups were exacerbations, cough, dyspnea and headache.

There were no reports of blurred vision, narrow-angle glaucoma or worsening of urinary retention, all of which are commonly reported adverse events for this class of medication, and in addition, reports of dry mouth were <0.5% in the revefenacin treatment arms.