Revefenacin is an investigational long-acting muscarinic antagonist (LAMA) and the first once-daily nebulized bronchodilator in development to treat COPD. The drug will be compatible with a range of jet nebulizers.
The Phase 3 clinical program of revefenacin, designed to support the product’s registration in the U.S., involved two replicate, ongoing, placebo-controlled 12-week clinical trials (NCT02512510, NCT02459080) evaluating the drug’s effectiveness.
A third open-label, single, active comparator 12-month safety clinical trial (NCT02518139) is being conducted in 1,050 COPD patients. Results from this trial are expected to be available in 2017.
The ongoing phase 3 efficacy and safety studies are testing two doses (88 mcg and 175 mcg) of revefenacin inhalation solution, administered once daily via nebulizer, in 2,300 patients with moderate to severe COPD.
In a press release, the companies announced that both effectiveness studies, involving more than 1,250 COPD patients, met their primary endpoint. After 12 weeks, treatment with revefenacin once daily, either at 88 mcg or 175 mcg, led to statistically significant improvements in lung function, assessed by forced expiratory volume in one second (FEV1), compared to a placebo.
In both trials, the improvements in FEV1 for revefenacin versus a placebo were 118 mL for 88 mcg, and 145 mL for 175 mcg.
Results from a pooled analysis showed that treatment with revefenacin increased FEV1 in a subgroup of COPD patients who were receiving therapies containing a long-acting beta agonist (LABA) (92 mL and 135 mL for 88 mcg and 175 mcg, respectively). FEV1 increases were also observed in a subgroup of COPD patients who were not taking any simultaneous LABA therapy (131 mL and 150 mL for 88 mcg and 175 mcg, respectively).
Both studies showed that treatment with either dose of revefenacin was well-tolerated, with no major treatment-related adverse events reported apart from exacerbations, cough, difficulty breathing, and headache.
The companies will present the data at future scientific meetings.
“We are extremely pleased with the outcome of these pivotal Phase 3 efficacy studies,” said Brett Haumann, MD, chief medical officer at Theravance. “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. These data confirm that revefenacin has the potential to offer meaningful benefits to patients with moderate to very severe COPD.”
“As the first once-daily nebulized bronchodilator of any class in late-stage development, combined with its compatibility with any standard jet nebulizer, revefenacin is uniquely positioned to address a key unmet need in the treatment of COPD. We look forward to completing our ongoing Phase 3 safety trial in 2017, with the goal of filing an NDA by the end of 2017,” Haumann added.
If all these Phase 3 clinical trials generate positive outcomes, Theravance anticipates filing a new drug application for revefenacin with the U.S. Food and Drug Administration (FDA) by the end of 2017.
“The positive results from these Phase 3 studies represent another exciting milestone in Mylan’s robust global respiratory pipeline,” said Mylan President Rajiv Malik. “We are very pleased with our collaboration with Theravance Biopharma and their work advancing this important program, and we look forward to continuing to work together to bring this product to market.
“We believe Mylan’s strong experience with nebulized products and experienced sales force in the respiratory segment, which has been further enhanced through our Meda transaction, will help ensure this product’s success if approved,” Malik added.