New Medicines

Yupelri Chronic obstructive pulmonary disease (COPD)


New molecular entity
Mylan UK

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Jan 22Currently no UK development plans [13,14].

Apr 19: Has been available in the US since at least Feb 19 [9].

Nov 18: Approved in US [8]

Nov 17: Theravance and Mylan have submitted the New Drug Application (NDA) to the FDA for revefenacin in the treatment of COPD, inhaled once daily by nebulisation. The application is based on the positive results from two pivotal PIII efficacy studies and the open-label PIII safety study [7].

Oct 16: regulatory filings planned by end of 2017 following completion of pivotal safety trial, NCT02518139 - results expected May 2017 [5].

Mar 15: US FDA has agreed to the design of the planned pivotal PIII programme for TD-4208, which is planned for later in 2015 [2].

Mar 15: PII in Germany, UK & US [2].


long-acting muscarinic antagonist (LAMA)
An estimated three million people are affected by COPD in the UK. About 900,000 have been diagnosed with COPD and an estimated two million people have COPD which remains undiagnosed. The rate of COPD in the population is estimated at between 2% and 4%. The diagnosed prevalence of COPD is 1.5%. The prevalence increases with age, with an estimated prevalence of 10% in men older than 75. [2]
Chronic obstructive pulmonary disease (COPD)

Trial or other data

July 17: Positive results from PIII safety study (NCT02518139~) of once-daily nebulised revefenacin in patients with COPD. RCT (n=1055) found rates of AEs were low and comparable to those seen in standard treatment arm (tiotropium via handheld device). These and other data will support licensing submission to FDA [6].

Oct 16: Theravance and Mylan announce two pivotal PIII studies (n=1250) meet primary efficacy endpoint of statistically significant improvements over placebo in trough FEV1 after 12 weeks (improvements across both studies of 118 and 145 mL for 88 and 175mcg doses once daily, respectively) [4].

Dec 15: Three PIII studies started in Sep 15. NCT02512510 and NCT02459080 are two 12-week, randomized, double-blind placebo-controlled studies of nebulized TD-4208 (88 or 175mcg) each in 618 subjects with COPD. The studies are due to complete Jun 16. NCT02518139 is a 52-week, randomized, active−controlled (tiotropium) study to evaluate the safety and tolerability of nebulized TD−4208 in 1050 Subjects with COPD. The study is due to complete Mar 17 [3]

Nov 14: Theravance Biopharma reports top-line results of a PII trial to assess the safety and efficacy of once- and twice-daily dosing with TD 4208 in patients with moderate to severe COPD (NCT02109172). Data revealed that lower dose TD 4208 (44µg) twice-daily dosing did not produce greater bronchodilation than the higher dose TD 4208 (175µg) once-daily dosing. The primary endpoint was weighted mean (0-24) FEV1 after the day 7 morning dose. The randomised, double-blind, placebo-controlled, cross-over trial was initiated in May 2014 and completed in October 2014, and enrolled 64 patients in the US. The trial was designed following input from the US FDA to test whether better efficacy could be achieved with a lower total dose given twice-daily than with a higher dose given once-daily [2].

Aug 14: Theravance completes a PIIb trial which evaluated safety and efficacy of four doses of TD 4208 in patients with moderate to severe COPD (NCT02040792). Patients were randomised to receive one of four doses of TD 4208 (44, 88, 175 or 350µg) or placebo once-daily for 28 days via a jet nebuliser, and the primary endpoint was trough FEV1. The trial was initiated in April 2014 and enrolled 355 patients (average age 62 years) in the US. Positive top-line results were announced in September 2014; the trial met its primary end-point, a significant change from baseline in trough FEV1 after the last dose of treatment on Day 28 [2].

Sep 13: Positive results of study 0091, a double-blind, multicenter, placebo-controlled PIIb RCT announced. Study 0091 evaluates the bronchodilatory effect, pharmacokinetics, safety and tolerability of multiple doses of TD-4208 in sixty-two moderate-severe COPD pts randomized to receive four of six doses of TD-4208 (22, 44, 88, 175, 350 or 700 mcg) and placebo once daily via a nebulizer during five 7-day study periods in an incomplete crossover study design. TD-4208 met the primary efficacy endpoint for all six doses studied and demonstrated a statistically significant change versus placebo from baseline in trough FEV1. The dose of 175 mcg was identified as the lowest that demonstrated a clinically meaningful change in FEV1 versus placebo at trough of 114 mL (95% CI: 76,153) [1].