Theravance Biopharma and Mylan N.V. have announced positive results from a 12-month phase 3 safety study of revefenacin (TD-4208), an investigational long-acting muscarinic antagonist (LAMA) and a proposed once-daily, nebulized bronchodilator in development for the treatment of chronic obstructive pulmonary disease (COPD). The study of 1,055 patients with COPD demonstrated that revefenacin was generally well-tolerated, and no new safety issues were identified. Rates of adverse events (AEs) and serious adverse events (SAEs) were low and comparable to those seen in the standard of care treatment arm.

“The data from this 12-month safety study build on our observations from the previous three-month efficacy studies and suggest that revefenacin has a favorable safety and tolerability profile when dosed chronically, either as a standalone therapy or when taken as an add-on to other COPD therapies including combinations of ICS and LABA,” said Brett Haumann, MD, chief medical officer at Theravance Biopharma. “As of today, there are no approved nebulized LAMAs, despite a significant number of COPD patients needing or preferring nebulized therapy for the treatment of their disease. Having achieved positive efficacy and tolerability data in our Phase 3 program, we and our partner Mylan believe that revefenacin is well positioned to address this important patient need. We remain on schedule to submit the NDA in the fourth quarter of 2017, which is the next step towards our goal of delivering the first once-daily nebulized bronchodilator to the COPD patient community.”

Mylan President Rajiv Malik commented, “Our revefenacin collaboration with Theravance Biopharma continues to deliver results at every step along the development path. We are very pleased with the top-line results from the 12-month safety trial and now feel we have all the data necessary to support a successful NDA filing. Should revefenacin receive approval from the FDA, we look forward to introducing this nebulized LAMA, to ensure the treatment has the greatest possible impact on the lives of patients with COPD.”

The Phase 3 safety study of revefenacin was a randomized, active-controlled parallel group trial designed to evaluate the safety and tolerability of two doses of revefenacin (88 mcg or 175 mcg, inhaled once daily via a nebulizer) over a dosing period of 52 weeks, as compared to standard of care. Tiotropium (Spiriva), administered via a handheld device, served as the active comparator standard of care treatment arm in the study. 50% of patients in the study were using other COPD therapies, including long-acting beta-agonists (LABA) or LABA/inhaled corticosteroids (ICS). Data from the trial demonstrated low rates of AEs and SAEs for both doses of revefenacin, comparable to tiotropium. Mortality rates were low, balanced across each arm of the study, and deemed by investigators as not related to study treatment. The most commonly reported adverse events were exacerbations, nasopharyngitis, upper respiratory tract infections, and cough. Rates of COPD exacerbations were numerically lowest in the 175 mcg arm. The numerical frequency of anti-muscarinic side effects such as dry mouth and constipation was lowest in the revefenacin arms. Theravance Biopharma and Mylan plan to present more detailed results from the study at upcoming scientific conferences.

The companies previously reported positive results from two pivotal Phase 3 efficacy studies of revefenacin, which included more than 1,250 patients with moderate to very severe COPD. In these studies, revefenacin demonstrated statistically significant and clinically meaningful improvements over placebo in trough forced expiratory volume in one second (FEV1) and in overall treatment effect on trough FEV1 (OTE FEV1) after 12 weeks of dosing. The data from these studies, combined with the results announced today, will support the submission of the new drug application (NDA) for revefenacin with the US Food and Drug Administration (FDA), anticipated in the fourth quarter of 2017.

Theravance Biopharma and its affiliates have partnered with Mylan and its affiliates on the development and commercialization of nebulized revefenacin products for COPD and other respiratory diseases. The companies are developing revefenacin as a once-daily, nebulized bronchodilator for the treatment of patients with COPD that will be compatible with a range of jet nebulizers.