Theravance COPD drug clears safety study, setting up NDA

Theravance Biopharma and Mylan are still on course to file for approval of their nebulized chronic obstructive pulmonary disease (COPD) therapy in the fourth quarter after posting 12-month safety data. The trial suggests revefenacin has a tolerable safety profile comparable to that of Boehringer Ingelheim’s bronchodilator Spiriva.

Investigators enrolled 1,055 COPD patients and randomized them to receive one of two doses of the experimental, nebulized long-acting muscarinic antagonist (LAMA) or Spiriva. Participants took revefenacin once a day for a year, at the end of which Theravance and Mylan compared the safety of their candidate to that of Spiriva.

Top-line data released by the partners suggest safety won’t scuttle revefenacin’s bid for approval. Both arms of the trial featured low rates of adverse events, be they serious or otherwise. The most common adverse events were exacerbations, nasopharyngitis, upper respiratory tract infections and cough. Theravance said the rate of COPD exacerbations was lowest in one of the revefenacin arms. The revefenacin also had numerically—but not statistically—fewer reports of dry mouth, constipation and other antimuscarinic side effects. 

With the safety data following on from positive efficacy readouts from two shorter phase 3 trials, Theravance and Mylan think they now have a package capable of winning FDA approval. The plan is to file an NDA in the fourth quarter.

Regulatory success would mark the end of a development program that has had its ups and downs. GlaxoSmithKline picked up the rights to revefenacin in 2004 but dropped the drug four years later after learning the formulation was incompatible with its proprietary inhaler. Theravance bounced back by repositioning revefenacin as a nebulized product. And, after posting phase 2 data, it landed a backloaded $265 million deal with Mylan in 2015. 

Theravance, an Irish-headquartered company that houses the vast majority of its employees in San Francisco, now sees the fact revefenacin is nebulized as its standout feature. No nebulized LAMAs are on the market today, giving Theravance and Mylan a shot at building a business upon the subset of COPD patients who need or prefer this form of delivery.