Theravance Biopharma and Mylan Report Positive New Data from Multiple Studies of YUPELRI™ (revefenacin) at the 2018 CHEST Annual Meeting
Details from the three CHEST presentations are as follows:
Efficacy in COPD Patients with Suboptimal PIFR – YUPELRI vs. Tiotropium
Researchers presented new data from a randomized, double-blinded study comparing the efficacy of YUPELRI to tiotropium in patients with moderate to very severe COPD and suboptimal peak inspiratory flow rates (PIFR) (< 60 L/min). 207 subjects were enrolled and randomized to receive either YUPELRI (175 mcg once daily) or tiotropium once daily for 28 days. Efficacy assessments included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
In the intent-to-treat population, the YUPELRI group showed improvements in trough FEV1 and trough FVC on day 29 compared with tiotropium group; however, these differences did not reach statistical significance. In the prespecified analysis of subjects with severe to very severe COPD (FEV1 < 50% predicted), which represented approximately 80% of the study population, YUPELRI demonstrated statistically significant improvements in trough FEV1 (p = 0.025) and FVC (p = 0.034) as compared to tiotropium. No new adverse events (AEs) were noted for either YUPELRI or tiotropium, and there were numerically fewer AEs observed in patients receiving YUPELRI (11.7%) compared to patients receiving tiotropium (37.5%).
"These results are noteworthy as this represents the first head-to-head study conducted between tiotropium dry powder via Handihaler and a nebulized treatment, such as YUPELRI. Furthermore, by focusing on COPD patients with suboptimal PIFR, the study provides important context around a patient group believed to be well positioned to benefit from once-daily, long-acting nebulized therapy," said
Efficacy in COPD Patients with Markers of More Severe Disease – Phase 3 Program Data Analysis
Researchers presented prespecified analyses of data from the YUPELRI Phase 3 program, highlighted by the demonstration of efficacy advantages for YUPELRI dosed at 175 mcg once daily compared to YUPELRI dosed at 88 mcg once daily in four subgroups of patients categorized as being at risk of COPD exacerbations based on markers of more severe COPD. The subgroups included patients on concomitant long-acting beta agonists (LABA), patients on inhaled corticosteroids (ICS), elderly patients (aged > 65 years in the 12-week efficacy trials, aged ≥ 65 in the 12-month safety trial) and patients classified as Global Initiative for Chronic Obstructive Lung Disease Category D (GOLD D).
Pooled data from the two replicate 12-week pivotal Phase 3 efficacy trials demonstrated that YUPELRI dosed at 175 mcg once daily produced greater improvements in trough FEV1 than YUPELRI dosed at 88 mcg once daily in each of the four analyzed subgroups. These efficacy trends favoring the 175 mcg once daily dose in the subgroups are consistent with those reported for the entire intent-to-treat population in the two Phase 3 efficacy trials.
Additionally, data from the 12-month Phase 3 safety trial demonstrated that YUPELRI dosed at 175 mcg once daily produced greater improvements in trough FEV1 than YUPELRI dosed at 88 mcg once daily in the LABA subgroup. The YUPELRI doses were equally effective at improving trough FEV1 in the ICS and elderly subgroups in the 12-month safety study.
Cardiovascular Safety: Review of Randomized, Controlled Trial Data, Including Phase 3 Program
Researchers conducted a review of cardiovascular (CV) safety data from four clinical studies of YUPELRI including the two replicate 12-week pivotal Phase 3 efficacy trials, the 12-month Phase 3 safety trial and a Phase 1 QT study in healthy subjects. The data analysis demonstrated that once-daily YUPELRI dosed for up to 52 weeks did not prolong QT interval or increase risk of major adverse cardiac events (MACE). Detailed findings include:
- Single YUPELRI doses of up 700 mcg did not have a clinically meaningful effect on cardiac repolarization (QTcF) in healthy patients.
- In the two Phase 3 efficacy studies in patients with moderate to very severe COPD, incidences of prolonged QTcF interval (> 450 msec in males, > 470 msec in females) were similar for placebo and YUPELRI dosed at 88 mcg once daily and 175 mcg once daily.
- In the Phase 3 safety trial in patients with moderate to very severe COPD, incidences of prolonged QTcF interval were similar for YUPELRI dosed at 175 mcg once daily and tiotropium, and slightly lower for YUPELRI dosed at 88 mcg once daily.
- There was no observed increased risk of MACE identified for either YUPELRI dose compared to tiotropium or placebo in the three Phase 3 clinical trials. Only one MACE seen in the Phase 3 program was considered possibly/probably related to YUPELRI.
COPD is a growing and devastating disease that is the third leading cause of death in the U.S.2 Nearly 15.7 million Americans (6.4%) report that they have been diagnosed with COPD and more are believed to be undiagnosed.3 There were more than 700,000 hospital discharges related to COPD in the U.S. reported in 2010. The costs of managing COPD in the U.S. were estimated to be nearly
YUPELRI (revefenacin) inhalation solution is a novel investigational once-daily nebulized LAMA under
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This press release includes statements that constitute "forward-looking statements", including with regard to: the outcome of clinical studies; that, if approved, YUPELRI would be the first and only once-daily, long-acting nebulized bronchodilator for the treatment of COPD; if approved, YUPELRI would be the first and only once-daily, long-acting single-agent product for COPD patients who require, or prefer, nebulized therapy; and that YUPELRI'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. These statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Because such statements inherently involve risks and uncertainties, actual future results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: success of clinical trials and our or our partners' ability to execute on new product opportunities; any regulatory, legal or other impediments to our or our partners' ability to bring products to market; other risks inherent in product development; the scope, timing, and outcome of any ongoing legal proceedings, including government investigations, and the impact of any such proceedings on our or our partners' businesses; actions and decisions of healthcare and pharmaceutical regulators, and changes in healthcare and pharmaceutical laws and regulations, in
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1 "Clinically meaningful" is defined by industry established Minimal Clinically Important Difference (MCID) for lung function (100 mL improvement in FEV1).
2 American Lung Association. "Chronic Obstructive Pulmonary Disease (COPD)" http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd. Accessed on September 29, 2016.
3 Center for Disease Control, COPD https://www.cdc.gov/copd/index.html. Accessed on January 3, 2018.
4 TBPH market research (N = 160 physicians); Refers to US COPD patients
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