PHASE III, DOUBLE-BLIND, RANDOMIZED, CONTROLLED, NON-INFERIORITY, PHASE III CLINICAL TRIAL TO EVALUATE THE EFFICACY OF SALBUTAMOL MONOTHERAPY COMPARED TO SALBUTAMOL PLUS IPRATROPIUM BROMIDE IN THE MANAGEMENT OF MODERATE ACUTE ASTHMATIC EXARCEBATIONS IN CHILDREN IN THE EMERGENCY DEPARTMENT

Start Date11 Apr 2025

Sponsor / Collaborator-

IRCT20230522058254N1

/ RecruitingPhase 3

Evaluation of the effect of ipratropium bromide spray on nasal hypersecretion (rhinorhea) in allergic rhinitis patients

Start Date21 Dec 2024

Sponsor / Collaborator-

CTR20243249

/ RecruitingNot Applicable

异丙托溴铵吸入气雾剂治疗慢性阻塞性肺疾病（COPD）的随机、双盲双模拟、单剂量、交叉的药效动力学研究

[Translation] A randomized, double-blind, double-dummy, single-dose, crossover pharmacodynamic study of ipratropium bromide inhalation aerosol in the treatment of chronic obstructive pulmonary disease (COPD)

主要目的：研究慢性阻塞性肺疾病（COPD）患者不同周期单次经口吸入异丙托溴铵吸入气雾剂的支气管扩张效应，通过随机、单剂量、交叉的设计，评价两制剂在COPD患者的PD-BE等效性，为受试制剂的生产注册申请提供支持。次要目的：观察受试制剂和参比制剂在COPD患者中的安全性。

[Translation]

Main purpose: To study the bronchodilator effect of single oral inhalation of ipratropium bromide inhalation aerosol in different cycles in patients with chronic obstructive pulmonary disease (COPD), and to evaluate the PD-BE equivalence of the two preparations in COPD patients through a randomized, single-dose, crossover design, to provide support for the production registration application of the test preparation. Secondary purpose: To observe the safety of the test preparation and the reference preparation in COPD patients.

Start Date05 Sep 2024

Sponsor / Collaborator

Jewim Pharmaceutical (Shandong) Co., Ltd

100 Clinical Results associated with Ipratropium Bromide

100 Translational Medicine associated with Ipratropium Bromide

100 Patents (Medical) associated with Ipratropium Bromide

2,214

Literatures (Medical) associated with Ipratropium Bromide

01 May 2025·DRUG METABOLISM AND DISPOSITION

Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail

Article

Author: Tzvetkov, Mladen V ; Morof, Felix ; Römer, Sarah ; Rönnpagel, Vincent ; Meyer-Tönnies, Marleen J

Transporters of the SLC22 family, such as organic cation transporter 1 (OCT1), possess very broad substrate specificity. It is unclear to what extent the inhibitory potencies of OCT1 depend on the substrate used. Here, we describe a multisubstrate drug cocktail that allows for the simultaneous testing of drug-drug interactions using 8 different victim drugs: fenoterol, salbutamol, sumatriptan, zolmitriptan, ipratropium, trospium, methylnaltrexone, and metformin. There were no significant differences in Michaelis constant (K_M) and v_max of the OCT1-mediated uptake of the substrates alone or in the cocktail. Depending on the victim drug analyzed, we observed 6.7-fold differences in the inhibitory potency of fenoterol (IC₅₀ of 0.75 μM for metformin and 5.1 μM for sumatriptan). Similarly, the inhibitory potency of verapamil varied 6.7-fold (IC₅₀ of 1.3 μM for zolmitriptan and 8.7 μM for ipratropium). Two groups of inhibitors showed strong correlations in their victim-dependent inhibitory potencies. Group 1 comprised verapamil, quinidine, fenoterol, and ipratropium, and group 2 comprised metformin, sumatriptan, and trimethoprim. By comparing OCT1 paralogs and orthologs, the broadest substrate spectra were observed for OCT1 and multidrug and toxin extrusion 1, followed by OCT2, multidrug and toxin extrusion 2-K, and OCT3. In contrast, organic cation transporters novel 1 and organic cation transporters novel 2 exhibited very narrow substrate specificity, transporting only L-carnitine and L-ergothioneine, respectively. In conclusion, OCT1 demonstrates substantial differences in inhibitory potencies, depending on the victim drug used. We developed a cocktail approach that enables rapid screening for such differences, facilitating the identification of drug-drug interactions at the early stages of drug development. This approach can be extended to other transporters with broad substrate specificity. SIGNIFICANCE STATEMENT: Polyspecific transporters have a broad substrate-binding cavity with no defined single binding position. Consequently, inhibitors may exhibit different inhibitory potencies depending on the victim drug used for testing. Here, we demonstrate this for organic cation transporter 1 (OCT1, SLC22A1) and presents a drug cocktail designed to identify varying inhibitory potencies in vitro and prevent false-negative drug-drug interaction results during early drug development. This approach can be extended to other polyspecific drug transporters.

18 Mar 2025·Current drug research reviews

Evaluation of Respirable Fraction by using Next Generation Impactor of Levosalbutamol Sulphate and Ipratropium bromide Metered Dose Inhaler

Article

Author: Dhalani, Jayesh ; Chilka, Chirag

Introduction::

A lung condition in which the passage of air into the lungs is obstructed, is treated using a combination pharmaceutical aerosol (Pressurised Metered dosage Inhaler) dosage form, such as Levosalbutamol Sulphate (LS) and Ipratropium Bromide (IB) pressurized inhalation solution, which contains 50 μg and 20 μg, respectively. Aerodynamic particle size distribution (APSD) aids in comprehending the likelihood of particle deposition in the lungs. In addition to being crucial for the efficacy and safety of medications, the respirable fraction is a significant critical quality attribute (CQA) for nasal and orally inhaled medicinal formulations.

Aim::

The evaluation of in-vitro respirable fraction utilizing Next Generator Impactor (NGI) simulates drug particle deposition in the patient's lungs. The current study used a sensitive highpressure liquid chromatography technique to assess the deposited respirable fraction through APSD from NGI, as aerodynamic properties of the delivered dosage.

Materials and methods::

The samples are subjected to NGI and analyzed on an X-bridge C18 (50 x 4.6), 3.5 μm with 35°C column oven, volume of injection 100 μL, and 0.5 mL per min flow rate using a mobile phase that is a 75:25% v/v combination of Heptane sulphonic acid sodium salt buffer and Acetonitrile in high-pressure liquid chromatography. The designed approach was validated for its anticipated function and determined the respirable fraction of the delivered dose.

Results::

The respirable fraction (fine particle dose) in μg for Levosalbutamol sulfate and Ipratropium bromide were observed 27.644 ± 1.9 and 11.045 ± 1.8, respectively. The fine particle fraction in percentage for Levosalbutamol sulfate and Ipratropium bromide were observed 55 ± 1.8 and 56 ± 1.8, respectively.

Conclusions::

The reliable results generated by novel combined in-vitro evaluation of LS and IB respirable fractions - correspond to lung deposition in a clinical study, which is about ≤ 5μm particle size in given doses of LS and IB inhalers.

01 Feb 2025·EMERGENCY MEDICINE JOURNAL

Nebulised high-dose corticosteroids as add-on therapy for adults with asthma exacerbation: a randomised controlled trial

Article

Author: Saiphoklang, Narongkorn ; Chormai, Nattaya ; Limjindaporn, Chitlada ; Kornthatchapong, Kumpol ; Chatchairatanavej, Nat ; Sri-On, Jiraporn ; Srivilaithon, Winchana

Background:

Evidence regarding high-dose inhaled corticosteroids (HDICS) in asthma exacerbations in adults is insufficient. This study compares the treatment outcomes of HDICS as add-on therapy to the outcomes of standard treatment in adult patients with acute asthma exacerbation in the ED.

Methods:

This was a single-centre, triple-blind, randomised controlled trial conducted in the ED in Thailand between March 2022 and April 2023. Adult patients with asthma exacerbation were randomly assigned to receive either a placebo (normal saline) or HDICS (budesonide 9000 µg) nebulisation combined with beta agonist and ipratropium within the first hour. The primary endpoints were length of ED stay, hospital admission and ED revisit. The secondary endpoints were dyspnoea scale, pulmonary functions, length of hospital stay and home exacerbation after ED discharge.

Results:

A total of 88 patients were randomly assigned to one of two groups: 44 patients received a HDICS and 44 patients were placed in the control group. The HDICS group had a significantly shorter ED length of stay (adjusted mean difference −133.6 min; 95% CI −242.4 to −24.8 min; p=0.016), and a higher proportion of ED discharged home within 8 and 16 hours compared with the control group. However, there were no significant differences between the two groups in hospital admission rates, ED revisit, dyspnoea scale, pulmonary functions, length of hospital stay or home exacerbation after ED discharge.

Conclusions:

HDICS may be useful as an add-on therapy to standard treatment for asthma exacerbation in adults to reduce ED stay.

Trial registration number:

TCTR20201214001.

News (Medical) associated with Ipratropium Bromide

07 Jan 2025

·endpts.com

Drugmakers cut some list prices, shrinking room for rebates in cancer, asthma and diabetes

Bayer’s Nexavar and Boehringer Ingelheim’s Spiriva are among a handful of drugs with reduced US list prices for the new year, according to a Tuesday analysis that showed average prices growing at their slowest rate in years. Bayer cut the list price of its cancer drug Nexavar in half, effective Jan. 1, according to data compiled by Drug Channels Institute (DCI). The list prices for Merck’s diabetes drugs Janumet XR and Januvia were cut by 42.4%. And Boehringer reduced the list price of its asthma drug Spiriva by 36.7% and Atrovent, which is used to treat chronic obstructive pulmonary disease, by 35.0%. On average, list prices last year for brand-name drugs grew at their lowest rate in a decade, according to the analysis. In 2024, they were up 2.3%, compared with 5% between 2019 and 2024, according to Drug Channels. Most patients don’t pay list prices, which are used as a starting point for negotiations with insurers, who typically pay a far lower net price, pocketing some of the difference in the form of rebates that can be used as incentives to prefer one drug over another. Those rebates have become an increasingly powerful force in price negotiations over the years, though they have also caused significant scrutiny of the insurance and pharmacy benefit management industry. And as list prices have risen, the handful of patients who buy drugs without insurance, or who pay a percentage of the list price, have faced financial pain from that dynamic. The shift to reduced list prices may partly be drugmakers’ reaction to the Inflation Reduction Act, which for the first time allows the federal government to directly negotiate drug prices with manufacturers. The law targets drugs with high Medicare spending based on list costs. That could “encourage manufacturers to narrow large gross-to-net gaps so as to bypass a drug’s selection by CMS,” DCI president Adam Fein said in his analysis. But Fein told Endpoints News Tuesday that the IRA won’t necessarily reduce the gross-to-net price gap for drugs not part of the negotiation process. He said that the law will still “encourage Part D plans to prefer high-list, high-rebate specialty drugs, even as the government and manufacturers will prefer a low list-price version.” A Merck spokesperson said the company lowered the list prices of its diabetes drugs to “align the list price more closely to the net price.” The price decrease is “unrelated” to the Medicare drug price negotiation process, the spokesperson said. Januvia was included in a list of drugs to face negotiations last year. The Centers for Medicare & Medicaid Services is slated to announce the second round of drugs selected for negotiation by Feb. 1. A Boehringer spokesperson said list price reductions are part of its “normal business practices” and that its action reflects the company’s “ongoing commitment to patient affordability and access.” A representative for Bayer didn’t immediately respond to a request for comment. Bayer’s and Boehringer’s drugs were not included in last year’s IRA list. Editor’s note: Updates article with comment from Boehringer.

12 Nov 2024

·www.prnewswire.com

Sanofi/Regeneron Pharmaceuticals' DUPIXENT Approval Marks a Significant Shift in Chronic Obstructive Pulmonary Disease Treatment Landscape | DelveInsight

After over a decade without notable progress in treating chronic obstructive pulmonary disease, patients with this ongoing condition now have two new treatment options, with more expected in the future. Regeneron and Sanofi recently revealed that the FDA has expanded the approved uses of their widely successful drug DUPIXENT to include COPD treatment. This marks the drug's sixth approved indication in the US, following its first approval seven years ago for atopic dermatitis. LAS VEGAS, Nov. 12, 2024 /PRNewswire/ -- Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterized by obstructed airflow, making breathing difficult. It primarily encompasses two main conditions: chronic bronchitis and emphysema, often coexisting. COPD typically develops due to long-term exposure to irritants such as cigarette smoke, air pollution, or occupational dust. As per DelveInsight analysis, the diagnosed prevalent population of COPD in the 7MM was around 44 million in 2023. These cases of COPD in the 7MM are expected to increase at a significant CAGR of 1.4% throughout the study period (2020–2034). As per the estimates, the majority of cases of COPD are in females as compared to males, in the US. But in EU4 and the UK, and Japan the diagnosed cases of males represent the majority of the cases. Overall, in the 7MM, females are predominantly high in number. In 2023, the US had around 3 million, 9 million, 5 million, and 1 million cases of GOLD 1, GOLD 2, GOLD 3, and GOLD 4, respectively based on the severity of airflow limitation. Estimates suggest that airflow limitation was higher in GOLD 2 severity. Various types of medications are used to manage COPD symptoms and complications, including bronchodilators, which help relax the muscles around the airways. This relaxation opens the airways and makes breathing easier. Most bronchodilators are administered via an inhaler. In more severe cases, the inhaler may also contain steroids to reduce inflammation. Some commonly used short-acting and long-acting bronchodilators for COPD management include Albuterol (ProAir HFA, Ventolin HFA, and others), Ipratropium (Atrovent HFA), Levalbuterol (Xopenex), Aclidinium (Tudorza Pressair), Arformoterol (Brovana), and Formoterol (Perforomist). In the LABA category, medications such as Striverdi Respimat, Arcapta/Onbrez, Serevent, and Brovana are included, while the LAMA class features drugs like Spiriva (available as Spiriva HandiHaler and Spiriva Respimat), Tudorza Pressair, Incruse Ellipta, Yupelri, Seebri Neohaler, and Lonhala Magnair. Since the generic version of Brovana was approved in April 2020, its market share has declined. Additionally, Arcapta Neohaler, Seebri Neohaler, and Utibron Neohaler were discontinued in the US in March 2020, which means they no longer contribute to market size. Patients who do not respond to single therapies are often prescribed double or triple therapy. Among the double therapies, the LABA+ICS combination is widely recommended, with drugs such as Symbicort, Breo Ellipta, and Advair. There are also LABA+LAMA combinations, including Anoro Ellipta, Stiolto Respimat, and Bevespi Aerosphere. In July 2020, the US FDA approved AstraZeneca's BREZTRI AEROSPHERE for the maintenance treatment of patients with COPD. Additionally, in October 2020, TRIXEO AEROSPHERE (a combination of formoterol fumarate, glycopyrronium bromide, and budesonide) received marketing authorization in the EU for the maintenance treatment of adult patients with moderate to severe COPD who are not adequately controlled by either a combination of an ICS and LABA or a LABA and LAMA. Currently, two triple combination therapies are available in the US: BREZTRI and TRELEGY ELLIPTA. Learn more about the FDA-approved COPD drugs @ Drugs for COPD Treatment Recently, Sanofi/Regeneron Pharmaceuticals' DUPIXENT added one more jewel to its crown by getting a label expansion nod for COPD from the FDA, EU, and NMPA. DUPIXENT's approval as the first targeted therapy for COPD represents a significant advancement in the treatment landscape for the disease. Unlike conventional treatments, which largely aim to manage symptoms, DUPIXENT specifically targets the IL-4 and IL-13 pathways linked to type 2 inflammation, a key driver in a subset of COPD patients. This precision in targeting allows for a more tailored treatment, especially for patients with elevated eosinophils, who often experience more frequent exacerbations and worse outcomes. The Phase III BOREAS trial demonstrated that patients treated with DUPIXENT experienced a 30% reduction in moderate-to-severe exacerbations over 52 weeks, significant improvements in lung function, and enhanced quality of life. By Week 52, those on DUPIXENT had improved prebronchodilator FEV1 by 160 mL compared to 77 mL in the placebo group. DUPIXENT was also well-tolerated, with a low frequency of adverse events. These results suggest that DUPIXENT could drastically shift COPD management by reducing exacerbations, improving lung function, and offering a safer, targeted therapy for patients with type 2 inflammation. To know more about COPD treatment options, visit @ New Treatment for COPD The chronic obstructive pulmonary disease pipeline possesses potential drugs in mid-stage developments to be launched in the near future. Itepekimab (Sanofi/Regeneron Pharmaceuticals), Benralizumab (AstraZeneca), Tezepelumab (Amgen/AstraZeneca), Mepolizumab (GSK), and others shall further create a positive impact on the market. Discover which therapies are expected to grab major COPD market share @ COPD Market Report Itepekimab is a fully human monoclonal antibody that targets interleukin-33 (IL-33), a protein involved in both type 1 and type 2 inflammation. The drug is administered via subcutaneous injection. Preclinical studies demonstrated that REGN3500 effectively inhibited several markers of both inflammatory types. Regeneron and Sanofi are investigating REGN3500 in diseases related to respiratory and dermatological inflammation. Currently, REGN3500 is in a Phase III clinical trial for COPD and was developed using Regeneron's VelocImmune technology, which produces optimized fully human antibodies. The development is part of a global collaboration between Regeneron and Sanofi. FASENRA (benralizumab) is a humanized recombinant monoclonal antibody of the IgG1k immunoglobulin type that selectively targets the alpha chain of the interleukin 5 receptor (IL-5R) found on eosinophils and basophils. It prevents IL-5 from binding and stops the hetero-oligomerization of the IL-5R's alpha and beta subunits, thereby inhibiting signal transduction. Additionally, it is an afucosylated IgG, which enhances its affinity for the FcγRIIIα receptor on natural killer cells, macrophages, and neutrophils. Approved by the FDA in November 2017 for severe eosinophilic asthma, benralizumab was developed by MedImmune, AstraZeneca's global biologics R&D division. The company is currently conducting Phase III clinical trials for FASENRA as a treatment for COPD. TEZSPIRE (tezepelumab), a pioneering human monoclonal antibody created by Amgen and AstraZeneca, has shown considerable therapeutic potential for various respiratory conditions. Originally intended for treating COPD, TEZSPIRE has yielded encouraging results in decreasing moderate-to-severe exacerbations in patients with high blood eosinophil counts. Recent findings from the Phase IIa COURSE Trial, unveiled at the ATS 2024 conference, underscored TEZSPIRE's effectiveness in minimizing COPD exacerbations among patients with different eosinophil levels. Mepolizumab is currently undergoing Phase III clinical trials for COPD, particularly in patients with frequent exacerbations and elevated eosinophil levels. It is available as an injectable solution and a powder for reconstitution for subcutaneous administration. The IL-5 receptor complex activates several signaling pathways that lead to the release of cytokines, neuromediators, chemokines, and various kinases, which facilitate eosinophil differentiation, proliferation, recruitment, and degranulation. Mepolizumab works by inhibiting the formation of the IL-5 receptor complex, thereby preventing eosinophil activation. This disruption affects normal eosinophil maturation and function, leading to decreased eosinophilic airway inflammation and reduced eosinophil survival. Discover more about drugs for COPD in development @ COPD Clinical Trials The anticipated launch of these emerging therapies for COPD are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the COPD market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for COPD in the 7MM is expected to grow from USD 16 billion in 2023 with a significant CAGR of 5% by 2034. This growth is mainly driven by the rise in the number of prevalent cases of COPD, ongoing clinical research, and better diagnostic tools that might improve the prognosis of the disease. DelveInsight's latest published market report titled as Chronic Obstructive Pulmonary Disease Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the COPD country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The COPD market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of COPD Subtype-specific Diagnosed Prevalent Cases of COPD Gender-specific Diagnosed Prevalent Cases of COPD Age-specific Diagnosed Prevalent Cases of COPD Diagnosed Prevalent Cases of COPD Based on Severity of Airflow Limitation Diagnosed Prevalent Cases of COPD Based on Symptoms and Exacerbation History The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM COPD market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this COPD market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the COPD market. Also, stay abreast of the mitigating factors to improve your market position in the COPD therapeutic space. Related Reports Chronic Obstructive Pulmonary Disease Pipeline Chronic Obstructive Pulmonary Disease Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key COPD companies, including Sanofi, Chiesi Farmaceutici S.p.A., United Therapeutics Corporation, Verona Pharma plc, Immunotek, Yungjin Pharm. Co., Ltd., Pulmotect, Inc., Tetherex Pharmaceutical, CSL Behring, AstraZeneca, Novartis, Genentech, Vertex Pharmaceuticals, EmeraMed, Afimmune, Mereo BioPharma, Synairgen, Adamis Pharmaceuticals, Quercegen Pharmaceuticals LLC, Regend Therapeutics, Meridigen Biotech Co., Ltd., Pulmatrix, Eisai, GlaxoSmithKline, EpiEndo Pharmaceuticals, 3SBio, OmniSpirant, Foresee Pharmaceuticals, Amgen, Organicell Regenerative Medicine, Arrowhead Pharmaceuticals, ProterixBio, RS BioTherapeutics, MitoRx, C4X Discovery, Respiratorius, ARK biosciences, Incannex, GNI Pharma, Celon pharma, Alveolus Bio, Kinaset therapeutics, Landos Biopharma, Parion Sciences, KeyMed Biosciences, Bioneer corporation, AlgiPharma, Palobiofarma, Dimerix Bioscience, Glenmark Pharmaceuticals, among others. Asthma Market Asthma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key asthma companies including GlaxoSmithKline, 4D Pharma plc, AstraZeneca, Suzhou Connect Biopharmaceuticals, Avillion, Pearl Therapeutics, ARS Pharmaceuticals, Sinomab, Avalo Therapeutics, Kymab, Sanofi, Cumberland Pharmaceuticals, Genentech, Inc. , among others. Asthma Pipeline Asthma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key asthma companies, including Jiangsu Hengrui Medicine, GlaxoSmithKline, Immunotek SL, AB Science, EMS, Avalo Therapeutics, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., ARS Pharmaceuticals, Sanofi, Zura Bio Ltd., AstraZeneca, EURRUS Biotech GmbH, T-Balance Therapeutics GmbH, Gossamer Bio, Aldeyra Therapeutics, Inc., Trio Medicines, Janssen Research & Development, Arrowhead Pharmaceuticals, Hoffman-La-Roche, GlaxoSmithKline, Biohaven Pharmaceutical, TAK-Circulator Co., Shanghai Hengrui Pharmaceutical, among others. Acute Respiratory Distress Syndrome Market Acute Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key ARDS companies, including MediciNova, Edesa Biotech, Light Chain Biosciences, Boehringer Ingelheim, Genentech, Windtree Therapeutics, Biomarck Pharmaceuticals, Athersys, Healios, Direct Biologics, Biohaven Pharmaceutical, Arch Biopartners, APEPTICO Forschung und Entwicklung GmbH, Staidson (Beijing) Biopharmaceuticals, Veru, Mesoblast Limited, Avalo Therapeutics, Pluristem Therapeutics, ILTOO Pharma, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalPhase 3Phase 2

18 Oct 2024

·www.prnewswire.com

Theravance Announces Publication of YUPELRI® (revefenacin) Area Under the Curve Spirometry Analysis in the International Journal of Chronic Obstructive Pulmonary Disease

DUBLIN, Oct. 18, 2024 /PRNewswire/ -- Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) today announced the publication of a sub-study of the pivotal 12-week, randomized, registrational revefenacin Phase 3 trials (Trials 0126 [NCT02459080] and 0127 [NCT02512510]) for YUPELRI, the first and only FDA approved once-daily nebulized long-acting muscarinic antagonist (LAMA), evaluating the area under the curve (AUC) lung function effects in moderate-to-very-severe chronic obstructive pulmonary disease (COPD) patients. These data and analyses, published in the International Journal of Chronic Obstructive Pulmonary Disease, reinforce that YUPELRI provides consistent and durable improvements in lung function, as compared with placebo, over a full 24-hours. "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 Hanover, NH and Pulmonologist and Respiratory Director at Valley Regional Hospital in Claremont, NH. "It provides additional valuable clinical insight into the duration and consistency of revefenacin over the entire dosing interval." 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 U.S. LAMAs are recognized by international COPD treatment guidelines as a cornerstone of maintenance therapy for COPD. 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 . 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 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 . 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: [email protected] 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. SOURCE Theravance Biopharma, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultDrug ApprovalLicense out/in

100 Deals associated with Ipratropium Bromide

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KEGG	Wiki	ATC	Drug Bank
D02212	Ipratropium Bromide	R03BB01 R01AX03	DBSALT000208

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Rhinitis, Allergic, Seasonal	United States	Boehringer Ingelheim Pharmaceuticals, Inc.	27 Oct 2000
Common Cold	United States	Boehringer Ingelheim Pharmaceuticals, Inc.	20 Oct 1995
Rhinitis	United States	Boehringer Ingelheim Pharmaceuticals, Inc.	20 Oct 1995
Bronchial Spasm	United States	Boehringer Ingelheim Pharmaceuticals, Inc.	29 Sep 1993
Pulmonary Disease, Chronic Obstructive	United States	Boehringer Ingelheim Pharmaceuticals, Inc.	29 Sep 1993
Asthma	Japan	Teijin Pharma Ltd.	25 Oct 1980
Bronchitis, Chronic	Japan	Teijin Pharma Ltd.	25 Oct 1980
Pulmonary Emphysema	Japan	Teijin Pharma Ltd.	25 Oct 1980

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic lung disease	Phase 3	Netherlands	Boehringer Ingelheim GmbH	01 Oct 2002

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00521222 (ARGARG, CTgov)	Not Applicable	Asthma	90	Albuterol HFA+Ipratropium HFA+Fluticasone (Arg/Arg Genotype on Advair (Fluticasone With Salmeterol) HFA)	oxkjazsrti(esgdgzmyra) = rwjyumpowp hrmkihstmx (ivhrqiogbp, 69.6) View more	-	21 Apr 2023
				Albuterol HFA+Ipratropium HFA+Fluticasone (Gly/Gly Genotype on Advair (Fluticasone With Salmeterol) HFA)	oxkjazsrti(esgdgzmyra) = tndlcuyqvv hrmkihstmx (ivhrqiogbp, 29.7) View more
NCT00583778 (CTgov)	Not Applicable	Acute asthma	141	ipratropium (Levalbuterol)	ghktwmjwwo = nojdethzlt xnpskxukre (pbbnmxvbdi, oznyzuihzm - arezqzumnp) View more	-	16 May 2022
				ipratropium (Levalbuterol Plus Ipratropium)	ghktwmjwwo = qxeffbaxwd xnpskxukre (pbbnmxvbdi, bashpllnxq - mlasahamww) View more
NCT03219866 (CTgov)	Phase 4	Pulmonary Disease, Chronic Obstructive \| Disease Progression	40	Nebulizers+Pulmicort+Brovana+Atrovent (Nebulizers)	iybmthslai(vgnlkkhsua) = tvsnqrzczi fumeefctbi (aabmyedpyy, 25.2) View more	-	10 Jun 2021
				Dry Powder Inhaler+Spiriva HandiHaler+Advair Diskus (Dry Powder Inhaler)	iybmthslai(vgnlkkhsua) = jezkywrkek fumeefctbi (aabmyedpyy, 19.8) View more
NCT01691079 (STAMINA, CTgov)	Phase 4	Asthma, Exercise-Induced	20	Placebo (Placebo)	raojhecwgx(uyhcbrnyrb) = xlwpxpbknw fdchioosjm (dcyimodren, bxfcpxyyri - qxqasnmtbm) View more	-	05 Jun 2020
				ipratropium bromide (Ipratropium Bromide)	raojhecwgx(uyhcbrnyrb) = ydwgkmbddz fdchioosjm (dcyimodren, fopyyupzpq - uimvxxfpyt) View more
NCT01696214 (SAPS, CTgov)	Phase 4	Asthma	20	ipratropium (Ipratropium)	slqpvocwmr(jzpxencbjd) = zdwuiejzxy rpbgcjmkmo (kngocvshoz, mlkulczzwi - fqklsshjhy) View more	-	12 Oct 2016
				Theophylline 400 mg (Theophylline)	slqpvocwmr(jzpxencbjd) = codmaowino rpbgcjmkmo (kngocvshoz, vihlcvlypk - jfuphckwal) View more
NCT01943552 (CTgov)	Phase 4	Pulmonary Disease, Chronic Obstructive	192	placebo	ymlkxeqbvj(obqzvcnqzl) = nxresaothb dgggupnkch (kgxbichanx, 29.35) View more	-	12 Sep 2016
NCT01987219 (CTgov)	Phase 3	Dysautonomia, Familial	15	Albuterol-sulphate (Albuterol-sulphate)	emppbbahjm(kejqrkoldy) = covskuzhie tijpczziyc (ygrnbzlxcd, 13.6) View more	-	02 Jun 2016
				Ipratropium-bromide (Ipratropium-bromide (Atrovent ®))	emppbbahjm(kejqrkoldy) = urwsstepxs tijpczziyc (ygrnbzlxcd, 10.9) View more
ACTRN12607000383460 (Pubmed \| J Paediatr Child Health)	Not Applicable	Childhood asthma	-	Salbutamol, Prednisolone, and Ipratropium Bromide	iasjajvalx(bbyjtiqyiv) = nzspgytnvu ldaoiwvsps (uzrfcrgsvv ) View more	-	01 Feb 2015
				Salbutamol and Prednisolone	iasjajvalx(bbyjtiqyiv) = umujeoeyyn ldaoiwvsps (uzrfcrgsvv ) View more
NCT01415518 (SECURE2, CTgov)	Phase 4	Pulmonary Disease, Chronic Obstructive	581	Theophylline+Symbicort Turbuhaler+Ipratropium (Symbicort Turbuhaler + Ipratropium + Theophylline SR)	xnwneeuvsp(kupytayphx) = hvpbnhdqma scwugtrfdi (yyffdniybg, qxebkpnyct - jgtqfbrdno) View more	-	26 Aug 2014
				Theophylline+Ipratropium (Ipratropium + Theophylline SR)	xnwneeuvsp(kupytayphx) = qzwpgxkwly scwugtrfdi (yyffdniybg, eyvxfreciu - lzpqfruekz) View more

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