Theravance Biopharma and Mylan have reported positive results from two replicate Phase 3 efficacy studies of revefenacin (TD-4208), an investigational, long-acting muscarinic antagonist (LAMA) and the first once-daily, nebulised bronchodilator in development for the treatment of chronic obstructive pulmonary disease (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.
It indicated 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 (88mcg once daily and 175mcg once daily).
The study showed 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 megalitres (mL) and 145mL for 88mcg and 175mcg, respectively.
In pre-specified pooled analyses, revefenacin produced increases in trough FEV1 within the subgroup (38%) of patients using background long-acting beta agonist (LABA) containing therapies, as well as in the subgroup of patients who were not using concomitant LABA therapy.
The improvements in FEV1 for the LABA subgroup were 92mL and 135mL for 88mcg and 175mcg respectively, and for the non-LABA subgroup were 131mL and 150mL for 88mcg and 175mcg, respectively.
The trials also indicated that the 88mcg and 175mcg 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, however, 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 less than 0.5% in the revefenacin treatment arms.
Theravance Biopharma chief medical officer Brett Haumann said: "We are extremely pleased with the outcome of these pivotal Phase III efficacy studies.
“The impressive improvements in FEV1 have exceeded our expectations, particularly when one considers that in nearly 40% of the patients we added revefenacin to their existing LABA or LABA / ICS therapy.
“This data confirms that revefenacin has the potential to offer meaningful benefits to patients with moderate to very severe COPD.
"As the first once-daily nebulised bronchodilator of any class in late-stage development, combined with its compatibility with any standard jet nebuliser, revefenacin is uniquely positioned to address a key unmet need in the treatment of COPD.”