Theravance Biopharma, Inc. and Mylan N.V. announced the initiation of a phase 3 programme for revefenacin (TD-4208), an investigational long-acting muscarinic antagonist (LAMA) in development for the treatment of chronic obstructive pulmonary disease (COPD). The phase 3 programme, designed to support the registration of the product in the US, includes two replicate three-month efficacy studies and a single 12-month safety study.

"Despite the fact that once-daily LAMAs are the first-line therapy for patients with moderate-to-severe COPD, there still are no nebulized LAMA treatments available today. This unmet need is significant when one considers that approximately 9 per cent of COPD patients in the US currently use nebulizers for ongoing maintenance therapy, and a total of 41 per cent of US. COPD patients use nebulizers for bronchodilator therapy at some time during the course of their disease," said Brett Haumann, MD, senior vice president, clinical development at Theravance Biopharma.

"Based on data that we've generated to date, we believe that revefenacin possesses the product profile that could uniquely and effectively address this market need. We look forward to conducting this phase 3 programme in collaboration with our partner Mylan to generate the data required to support a regulatory filing for the product."

"The initiation of this phase 3 programme is an important milestone for Mylan as we continue to further build out our global respiratory pipeline. Revefenacin is highly complementary to our currently marketed nebulized COPD product, Perforomist Inhalation Solution, as well as other respiratory products in our pipeline. We are excited by the potential to offer healthcare professionals, and ultimately patients, an even more robust respiratory portfolio if revefenacin is approved," said Mylan president Rajiv Malik.

"Theravance Biopharma has done an excellent job advancing revefenacin to this stage of development and we look forward to contributing our expertise and leadership in the area of nebulized respiratory therapy as we work together to bring this important product to market."

The revefenacin development program includes two phase 3 efficacy studies and one phase 3 safety study, examining 2 doses (88 mcg and 175 mcg) of revefenacin inhalation solution administered once-daily via nebulizer in moderate to severe patients with COPD. The phase 3 efficacy studies are replicate, randomized, double-blind, placebo-controlled, parallel-group trials designed to provide pivotal efficacy and safety data for once-daily revefenacin over a dosing period of 12 weeks, with a primary endpoint of trough forced expiratory volume in one second (FEV1) on day 85. The phase 3 safety study is an open-label, active comparator study of 12 months duration. Together, the three studies will enroll approximately 2,300 patients. Theravance Biopharma expects the results to be available from the two efficacy studies in 2016, with the results of the safety study available in 2017.

Theravance Biopharma and Mylan N.V. and its affiliates have partnered to develop and commercialize nebulized revefenacin products for COPD and other respiratory diseases. Under the terms of the agreement, Theravance Biopharma is leading the US development programme for the revefenacin inhalation solution product, with all costs reimbursed by Mylan up until the approval of the first new drug application, after which costs will be shared. Mylan is responsible for ex-US development and commercialisation. Theravance Biopharma is eligible to receive up to $220 million in development and sales milestone payments, as well as a profit-sharing arrangement with Mylan on US sales and double-digit royalties on ex-US sales. Additionally, Theravance Biopharma retains worldwide rights to revefenacin delivered through other dosage forms, such as a metered dose inhaler or dry powder inhaler (MDI/DPI), and the rights to nebulized revefenacin in China.

COPD is a growing and devastating disease that is the third leading cause of death in the US. An estimated 12.7 million American adults are diagnosed with COPD and an almost equal number are believed to be undiagnosed. There were more than 700,000 hospital discharges in the US reported in 2010. The costs of managing COPD in the U.S. were estimated to be nearly $50 billion in 2010, including $29.5 billion in direct healthcare expenditures, $8 billion in indirect morbidity costs and $12.4 billion in indirect mortality costs.

Revefenacin (TD-4208), is a novel investigational LAMA in development for the treatment of COPD. Theravance Biopharma has completed a successful phase 2b programme with revefenacin, administered once-daily via nebulizer for up to 28 days in a moderate-to-severe COPD population. Market research by Theravance Biopharma indicates approximately 9 per cent of the treated COPD patients in the US use nebulizers for ongoing maintenance therapy. LAMAs are a cornerstone of maintenance therapy for COPD, but are only available in handheld devices that may not be suitable for every patient. Revefenacin has the potential to be a best-in-class once-daily single-agent product for COPD patients who require, or prefer, nebulized therapy. The product's stability in both metered dose inhaler and dry powder device formulations, suggest that this LAMA could also serve as a foundation for novel handheld combination products.