Theravance Announces Publication of YUPELRI® (revefenacin) Area Under the Curve Spirometry Analysis in the International Journal of Chronic Obstructive Pulmonary Disease
Theravance Biopharma announced the publication of a sub-study of pivotal Phase 3 trials for YUPELRI (revefenacin), the first FDA-approved once-daily nebulized long-acting muscarinic antagonist (LAMA) for COPD. The study, published in the International Journal of Chronic Obstructive Pulmonary Disease, evaluated the area under the curve (AUC) lung function effects in moderate-to-very-severe COPD patients.
Key findings include:
- Revefenacin improved bronchodilation versus placebo in COPD patients
- Rapid onset of bronchodilation was observed, with a mean FEV1 difference of 145 mL at 15 minutes
- Day 84 bronchodilation improvements were sustained over 24 hours vs. placebo
- FEV1 AUC measurements provide additional information on the magnitude and consistency of bronchodilation throughout the dosing interval
The study reinforces that YUPELRI provides consistent and durable improvements in lung function over a full 24-hour period.
Theravance Biopharma ha annunciato la pubblicazione di uno studio secondario di trial pivotali di Fase 3 per YUPELRI (revefenacina), il primo antagonista muscarinico a lunga durata d'azione (LAMA) nebulizzato, approvato dalla FDA per COPD. Lo studio, pubblicato nell'International Journal of Chronic Obstructive Pulmonary Disease, ha valutato l'area sotto la curva (AUC) degli effetti sulla funzionalità polmonare nei pazienti con COPS da moderata a molto grave.
I risultati chiave includono:
- La revefenacina ha migliorato la broncodilatazione rispetto al placebo nei pazienti con COPS
- È stata osservata una rapida insorgenza della broncodilatazione, con una differenza media FEV1 di 145 mL a 15 minuti
- I miglioramenti nella broncodilatazione al giorno 84 sono stati mantenuti per 24 ore rispetto al placebo
- Le misurazioni AUC FEV1 forniscono ulteriori informazioni sull'entità e la coerenza della broncodilatazione durante l'intervallo di dosaggio
Lo studio conferma che YUPELRI offre miglioramenti costanti e duraturi della funzionalità polmonare per un intero periodo di 24 ore.
Theravance Biopharma anunció la publicación de un estudio secundario de ensayos pivotal de Fase 3 para YUPELRI (revefenacina), el primer antagonista muscarínico de acción prolongada nebulizado (LAMA) aprobado por la FDA para COPD. El estudio, publicado en el International Journal of Chronic Obstructive Pulmonary Disease, evaluó el área bajo la curva (AUC) de los efectos en la función pulmonar en pacientes con EPOC de moderada a muy severa.
Los hallazgos clave incluyen:
- La revefenacina mejoró la broncodilatación en comparación con el placebo en pacientes con EPOC
- Se observó un inicio rápido de broncodilatación, con una diferencia media de FEV1 de 145 mL a los 15 minutos
- Las mejoras en la broncodilatación del día 84 se mantuvieron durante 24 horas en comparación con el placebo
- Las mediciones AUC de FEV1 proporcionan información adicional sobre la magnitud y consistencia de la broncodilatación a lo largo del intervalo de dosificación
El estudio refuerza que YUPELRI proporciona mejoras constantes y duraderas en la función pulmonar durante un período completo de 24 horas.
Theravance Biopharma는 YUPELRI (레베페나신)에 대한 3상 주요 임상시험의 하위 연구 발표를 알렸습니다. 이는 COPD를 위한 FDA 승인 최초의 하루에 한 번 사용하는 네뷸라이저 장기작용 무스카린 길항제(LAMA)입니다. 이 연구는 International Journal of Chronic Obstructive Pulmonary Disease에 발표되었으며, 중간에서 매우 심각한 COPD 환자의 폐 기능에서 곡선 아래 면적(AUC) 효과를 평가했습니다.
주요 발견은 다음과 같습니다:
- 레베페나신이 COPD 환자에서 위약 대비 기관지 확장을 개선했습니다.
- 15분 후 평균 FEV1 차이 145 mL로 신속하게 기관지 확장이 시작되었습니다.
- 84일째 기관지 확장 개선이 위약 대비 24시간 동안 지속되었습니다.
- FEV1 AUC 측정은 투약 간격 동안 기관지 확장의 크기와 일관성에 대한 추가 정보를 제공합니다.
이 연구는 YUPELRI가 24시간 동안 일관되고 지속적인 폐 기능 개선을 제공함을 확인합니다.
Theravance Biopharma a annoncé la publication d'une sous-étude des essais cliniques pivot de Phase 3 pour YUPELRI (revefenacine), le premier antagoniste muscarinique à action prolongée nebulisé (LAMA) approuvé par la FDA pour COPD. L'étude, publiée dans l'International Journal of Chronic Obstructive Pulmonary Disease, a évalué l'aire sous la courbe (AUC) des effets sur la fonction pulmonaire chez des patients atteints de BPCO modérée à très sévère.
Les résultats clés incluent :
- La revefenacine a amélioré la bronchodilatation par rapport au placebo chez les patients atteints de BPCO
- Un début rapide de bronchodilatation a été observé, avec une différence moyenne de FEV1 de 145 mL à 15 minutes
- Les améliorations de la bronchodilatation au jour 84 ont été maintenues pendant 24 heures par rapport au placebo
- Les mesures AUC de FEV1 fournissent des informations supplémentaires sur l'ampleur et la cohérence de la bronchodilatation tout au long de l'intervalle de dosage
L'étude renforce que YUPELRI offre des améliorations constantes et durables de la fonction pulmonaire sur une période complète de 24 heures.
Theravance Biopharma gab die Veröffentlichung einer Nebestudie zu den wegweisenden Phase-3-Studien für YUPELRI (Revefenacin) bekannt, dem ersten von der FDA zugelassenen, einmal täglich vernebelten langwirksamen muskarinischen Antagonisten (LAMA) für COPD. Die Studie, die im International Journal of Chronic Obstructive Pulmonary Disease veröffentlicht wurde, bewertete die Fläche unter der Kurve (AUC) der Lungenfunktionswirkungen bei Patienten mit moderater bis sehr schwerer COPD.
Wichtige Ergebnisse umfassen:
- Revefenacin verbesserte die Bronchodilatation im Vergleich zum Placebo bei COPD-Patienten
- Eine schnelle Bronchodilatation wurde beobachtet, mit einem durchschnittlichen FEV1-Unterschied von 145 mL nach 15 Minuten
- Die Verbesserungen der Bronchodilatation am Tag 84 hielten 24 Stunden im Vergleich zum Placebo an
- FEV1 AUC-Messungen bieten zusätzliche Informationen über die Größe und Konsistenz der Bronchodilatation über den Dosierungszeitraum hinweg
Die Studie bestätigt, dass YUPELRI konsistente und dauerhafte Verbesserungen der Lungenfunktion über einen vollständigen Zeitraum von 24 Stunden bietet.
- YUPELRI demonstrated consistent and durable improvements in lung function over 24 hours
- Rapid onset of bronchodilation with mean FEV1 difference of 145 mL at 15 minutes
- Sustained bronchodilation improvements on Day 84 with significant differences in FEV1 AUC measurements
- YUPELRI is the first and only FDA-approved once-daily nebulized LAMA for COPD
- None.
Insights
This publication provides significant clinical insights into YUPELRI's (revefenacin) efficacy in COPD treatment. The AUC analysis demonstrates consistent and durable improvements in lung function over 24 hours, which is important for COPD management. Key findings include:
- Rapid onset of action with clinically meaningful bronchodilation within 15 minutes
- Sustained bronchodilation over 24 hours, with significant improvements in FEV1 AUC across various time intervals
- Mean FEV1 differences well above the 100 mL MCID threshold
These results suggest YUPELRI could offer improved symptom control and quality of life for COPD patients. The once-daily nebulized formulation may enhance treatment adherence, potentially leading to better long-term outcomes. For Theravance Biopharma, this data strengthens YUPELRI's position in the competitive COPD market, potentially driving increased adoption and sales.
The publication of this sub-study in a peer-reviewed journal is a positive development for Theravance Biopharma. It provides robust clinical evidence supporting YUPELRI's efficacy, which could translate to several market advantages:
- Differentiation in a crowded COPD market by highlighting 24-hour bronchodilation
- Potential for increased physician confidence and prescription rates
- Support for payer negotiations and formulary inclusion
As the first and only FDA-approved once-daily nebulized LAMA, YUPELRI has a unique position. This data reinforces its value proposition, potentially leading to
"Where previous data showed that revefenacin significantly improved peak and trough FEV1 at Day 85 compared with placebo in patients with moderate-to-very-severe COPD, this subset post-hoc analysis depicts a more comprehensive view of 24-hour bronchodilation as assessed by examining AUC over multiple time periods," said Dr. Donald A. Mahler, Emeritus Professor of Medicine at Geisel School of Medicine at Dartmouth in
Dr. Blake LeMaster, Assistant Professor of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, commented, "Importantly, this drug also exhibits a substantial peak response as well as bronchodilation over the initial 2-hour period as exhibited by FEV1 AUC 0-2H." He added, "Clinically meaningful bronchodilation was seen within the first 15 minutes of administration, persisting over the 24-hour duration during which patients underwent serial spirometry. These data demonstrate that revefenacin can provide rapid and prolonged bronchodilation with just a single dose."
Key Study Findings:
- Analysis of a retrospective, pooled sub-study from Phase 3 Studies 0126 and 0127 demonstrated that revefenacin (n = 50) improved bronchodilation versus placebo (n = 47) in patients with moderate-to-very-severe COPD when assessed by FEV1 AUC.
- Rapid onset of bronchodilation was observed, with a mean FEV1 difference of 145 mL achieved at 15 minutes, exceeding the accepted Minimal Clinically Important Difference (MCID) of 100 mL with approximately
97.5% confidence. - Day 84 bronchodilation improvements were sustained over 24 hours vs. placebo, with mean differences of 282 mL, 220 mL, 205 mL and 212 mL for FEV1 AUC0–2h, AUC0–12h, AUC12–24h and AUC0–24h, respectively, (p<0.001 for all).
Trough FEV1 is an important endpoint often used in COPD trials and provides the magnitude of lung function benefit at the end of a given dosing interval. FEV1 AUC measurements provide additional information on the magnitude and consistency of bronchodilation throughout the dosing interval, including both daytime and nighttime effects. As patients depend on the magnitude of sustained bronchodilation to address COPD symptoms, combined use of both trough FEV1 and FEV1 AUC may allow for a more comprehensive assessment of bronchodilator efficacy to support clinical decision-making.
About Studies 0126 and 0127
Studies 0126 (placebo, n = 209; 88 mcg revefenacin, n = 212; and 175 mcg revefenacin, n = 198), and 0127 (placebo, n = 208; 88 mcg revefenacin, n = 205; and 175 mcg revefenacin, n = 197) were replicate Phase 3 studies which included adults ≥40 years old with documented moderate-to-very-severe COPD, and a current or past smoking history of ≥10 pack-years. Subjects were randomized 1:1:1 to receive revefenacin 88 mcg, revefenacin 175 mcg, or placebo administered once-daily in the morning by a standard jet nebulizer (PARI LC Sprint) for 12 weeks. The prespecified primary efficacy endpoint was change from baseline in trough FEV1 on Day 85. Peak FEV1 on Day 1 was a secondary endpoint and FEV1 AUC from 0 to 2 hours (FEV1 AUC0–2h) on Days 1, 15, 29, 57, and 84 was a prespecified exploratory endpoint1. While both revefenacin 88 mcg and 175 mcg doses were investigated in these trials, the post hoc analysis reported herein focused only on the 175 mcg dose as this is the dose approved by the FDA2.
About YUPELRI
YUPELRI® (revefenacin) inhalation solution is the first and only once-daily nebulized long-acting muscarinic antagonist (LAMA) approved for the maintenance treatment of COPD in the
Important Safety Information
What is YUPELRI®?
- YUPELRI is a prescription medicine used to treat chronic obstructive pulmonary disease (COPD), a long-term (chronic) lung disease that includes chronic bronchitis, emphysema, or both.
- It is an anticholinergic medicine which helps the muscles around the airway in your lungs stay relaxed to prevent symptoms such as wheezing, cough, chest tightness, and shortness of breath.
- It is used long-term as 1 vial of YUPELRI, 1 time each day inhaled through your nebulizer to improve symptoms of COPD for better breathing.
Who should not use YUPELRI?
- Do not use YUPELRI if you have sudden breathing problems. Always have a rescue inhaler with you.
- Do not use YUPELRI if you have had an allergic reaction to revefenacin, or any of the other ingredients in YUPELRI (sodium chloride, citric acid, sodium citrate).
- Do not use in children. It is not known if YUPELRI is safe and effective in children.
Before using YUPELRI, tell your healthcare provider about all your medical conditions, including if you:
- have eye problems such as glaucoma. YUPELRI may make your glaucoma worse.
- have prostate or bladder problems, or problems passing urine. YUPELRI may make these problems worse.
- have liver problems.
- are allergic to any of the ingredients in YUPELRI, or any other medicines.
- are pregnant or planning to become pregnant. It is not known if YUPELRI may harm your unborn baby.
- are breastfeeding. It is not known if the medicine in YUPELRI passes into your breast milk and if it can harm your baby.
Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. YUPELRI and certain other medicines may interact with each other. This may cause serious side effects.
Especially tell your healthcare provider if you take:
- Other anticholinergics (including tiotropium, ipratropium, aclidinium, umeclidinium, glycopyrrolate)
- Atropine
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist each time you get a new medicine.
What are the possible side effects with YUPELRI?
YUPELRI can cause serious side effects, including:
- Sudden breathing problems immediately after inhaling your medicine. If you have sudden breathing problems immediately after inhaling your medicine, stop using YUPELRI and call your healthcare provider right away.
- New or worsened eye problems including acute narrow-angle glaucoma. Acute narrow-angle glaucoma can cause permanent loss of vision if not treated. Symptoms may include:
- Red eyes
- Blurred vision
- Seeing halos or bright colors around lights
- Eye pain or discomfort
- Nausea or vomiting
- Urinary retention. People who take YUPELRI may develop new or worse urinary retention. Symptoms of urinary retention may include:
- difficulty urinating
- urinating frequently
- urination in a weak stream or drips
- painful urination
If you have any of these symptoms, call your healthcare provider right away before taking another dose.
- Serious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following symptoms of a serious allergic reaction:
- rash
- hives
- severe itching
- swelling of your face, mouth, and tongue
- difficulty breathing or swallowing
If you have any of these symptoms, stop taking YUPELRI, and call your healthcare provider right away before taking another dose.
- Common side effects of YUPELRI include:
- Cough
- Runny nose
- Upper respiratory tract infection
- Headache
- Back pain
Tell your healthcare provider if you get any side effects that bother you or that do not go away. These are not all the possible side effects with YUPELRI. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
How should I use YUPELRI?
Read the step by step instructions for using YUPELRI in the FDA-approved Prescribing Information and in the Patient Information Leaflet
- YUPELRI is only for use with a nebulizer.
- Do not use YUPELRI more often than prescribed.
- Do not mix YUPELRI with other medicines in your nebulizer.
- Do not use other medicines that contain an anticholinergic for any reason.
- Do not stop using YUPELRI, even if you are feeling better, unless your healthcare provider tells you to because your symptoms might get worse.
- Call your healthcare provider or get emergency medical care right away if
- your breathing problems get worse.
- you need to use your rescue inhaler medicine more often than usual.
- your rescue inhaler medicine does not relieve your symptoms.
This summary does not include all the information about YUPELRI and is not meant to take the place of a discussion with your healthcare provider about your treatment.
Please see the full prescribing information and instructions for use at www.yupelri.com
About Theravance Biopharma / Viatris Collaboration
Theravance Biopharma and Viatris Inc. and their respective affiliates have established a strategic collaboration to develop and commercialize nebulized revefenacin products for COPD.
About Theravance Biopharma
Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value.
For more information, please visit www.theravance.com.
THERAVANCE BIOPHARMA®, THERAVANCE® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries).
YUPELRI® is a registered trademark of Mylan Specialty L.P., a Viatris company. Trademarks, trade names or service marks of other companies appearing in this press release are the property of their respective owners.
Forward-Looking Statements
This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the Company's expectations regarding its future profitability, expenses and uses of cash, the Company's goals, designs, strategies, plans and objectives, future growth of YUPELRI sales, future royalty payments, the ability to provide value to shareholders, the Company's regulatory strategies and timing of clinical studies, possible safety, efficacy or differentiation of our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts; contingent payments due to the Company from the sale of the Company's TRELEGY ELLIPTA royalty interests to Royalty Pharma, and expectations around the use of OHSA scores as endpoints for clinical trials. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: factors that could increase the Company's cash requirements or expenses beyond its expectations and any factors that could adversely affect its profitability, whether milestone thresholds can be achieved, delays or difficulties in commencing, enrolling or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the Company's product candidates or product are unsafe, ineffective or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop, manufacture and commercialize products, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure, the ability of the Company to protect and to enforce its intellectual property rights, volatility and fluctuations in the trading price and volume of the Company's shares, and general economic and market conditions. Other risks affecting Theravance Biopharma are in the Company's Form 10-Q filed with the SEC on August 8, 2024, and other periodic reports filed with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law.
Contact:
investor.relations@theravance.com
650-808-4045
1Ferguson GT, Feldman G, Pudi KK, et al. Improvements in lung function with nebulized revefenacin in the treatment of patients with moderate to very severe COPD: results from two replicate Phase III clinical trials. Chronic Obstr Pulm Dis Apr. 2019;6(2):154–165. doi:10.15326/jcopdf.6.2.2018.0152
2 YUPELRI (revefenacin). Package Insert. Theravance Biopharma and Mylan Inc.; 2018.
View original content to download multimedia:https://www.prnewswire.com/news-releases/theravance-announces-publication-of-yupelri-revefenacin-area-under-the-curve-spirometry-analysis-in-the-international-journal-of-chronic-obstructive-pulmonary-disease-302280400.html
SOURCE Theravance Biopharma, Inc.
FAQ
What were the key findings of the YUPELRI (TBPH) sub-study published in October 2024?
How does YUPELRI (TBPH) differ from other COPD treatments?
What is the significance of FEV1 AUC measurements in the YUPELRI (TBPH) study?
