Clinical Trials

Date: 2017-05-23

Type of information: Presentation of results at a congress

phase:

Announcement: presentation of results at the American Thoracic Society (ATS) International Conference

Company: Mylan (USA - PA) Theravance (UK)

Product: revefenacin (TD-4208)

Action mechanism:

• long-acting muscarinic antagonist (LAMA). Revefenacin is 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).

Disease: chronic obstructive pulmonary disease (COPD)

Therapeutic area: Lung diseases - Respiratory diseases

Country:

Trial details:

• The three-month Phase 3 pivotal studies were 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. The replicate studies enrolled a combined total of over 1,250 patients in the U.S. across a range of disease severity from moderate to very severe COPD and allowed for the concomitant use of long-acting beta agonist (LABA) and/or long-acting beta agonist/inhaled corticosteroid (LABA/ICS) products in a significant proportion (38%) of the studied population. Study investigators tested two doses (88 mcg and 175 mcg) of revefenacin inhalation solution or matched placebo administered once daily via a standard jet nebulizer in moderate to very severe COPD patients.

Latest news:

• • On May 23, 2017, Theravance Biopharma and Mylan announced the presentation of additional efficacy and safety data from the three-month, pivotal Phase 3 studies of revefenacin (TD-4208) at the American Thoracic Society (ATS) International Conference. Researchers presented new data from the completed three-month Phase 3 studies, which included more than 1,250 patients with moderate to very severe COPD. A first presentation, which focused on efficacy outcomes, 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 in each study and for each of the revefenacin doses studied (88 mcg once daily and 175 mcg once daily). The improvements in trough FEV1, the primary efficacy endpoint, versus placebo for the intent-to-treat populations across both studies were 118 mL and 145 mL for 88 mcg and 175 mcg, respectively. Additionally, the improvements in OTE FEV1, a key secondary endpoint, versus placebo for the intent-to-treat population across both studies were 112 mL and 139 mL for 88 mcg and 175 mcg, respectively. A second presentation featured safety and tolerability data from the two completed three-month Phase 3 studies. Both doses of revefenacin had comparable rates of adverse events to placebo, low rates of serious adverse events, and no clinically meaningful differences in blood parameters or electrocardiogram (ECG) data, across all treatment groups (active and placebo). As previously reported, the most commonly reported adverse events, across both trials and across all treatment groups, were exacerbations, cough, dyspnea and headache. There were no reports of blurred vision, narrow-angle glaucoma or worsening of urinary retention. Reports of dry mouth were < 0.5% in the revefenacin treatment arms. The revefenacin Phase 3 program also includes an ongoing 12-month, open-label, active comparator safety study in more than 1,050 patients, which is expected to be completed in mid-2017. Together, the three studies enrolled approximately 2,300 patients. Should outcomes from the safety study be supportive, Theravance Biopharma expects to file a New Drug Application (NDA) for revefenacin with the FDA by the end of 2017.

Is general: Yes