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Umeclidinium bromide

Generic Name
Umeclidinium bromide
Brand Names
Anoro, Anoro Ellipta, Incruse Ellipta, Trelegy Ellipta, Rolufta Ellipta (previously Rolufta), Incruse Ellipta (previously Incruse)
Drug Type
Small Molecule
Chemical Formula
C29H34NO2
CAS Number
869185-19-3
Unique Ingredient Identifier
GE2T1418SV
Background

Umeclidinium is a long-acting muscarinic antagonist (LAMA) used as a maintenance treatment for symptoms of chronic obstructive pulmonary disease (COPD). COPD is a progressive obstructive lung disease characterized by shortness of breath, cough, sputum production, and chronically poor airflow with a forced expiratory volume in 1 second (FEV1) of less than 80%.

Maintenance of the airway is controlled by the parasympathetic nervous system, particularly by the abundance of the muscarinic subtype 3 (M3) in the airway smooth muscle. Parasympathetic ganglia are associated with the larger airways while postganglionic fibers innervate the smaller diameter bronchioles contributing to airway resistance. By blocking the M3 muscarinic receptor, umeclidinium inhibits the binding of acetylcholine and thereby opens up the airways by preventing bronchoconstriction. However, even though umeclidinium monotherapy is well-tolerated for up to 14 days, it is more likely to be used in combination therapy, as the international Gold Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommended the use of two long-acting bronchodilators with differing mechanisms of action to maximize efficacy and minimize adverse effects.

Umeclidinium was approved by the FDA in April 2014 under the brand name Incruse Ellipta as a standalone product. Later, it was further approved as a combination product with vilanterol and vilanterol/fluticasone furoate under the brand name ANORO ELLIPTA and TRELEGY ELLIPTA respectively.. ANORO ELLIPTA was approved in December 2013 while TRELEGY ELLIPTA was approved in September 2017.

Indication

Umeclidinium is approved by the FDA and Health Canada for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Additionally, umeclidinium also exists as combination products with vilanterol or vilanterol and fluticasone furoate. Both products were indicated for the maintenance treatment of COPD, but only the umeclidinium/vilanterol/fluticasone furoate product was approved for the maintenance treatment of asthma in patients aged 18 years and older.

Associated Conditions
Asthma, Chronic Obstructive Pulmonary Disease (COPD)

Zydus Healthcare Secures CDSCO Approval for Phase III Trials of Two COPD Combination Therapies

• Zydus Healthcare has received approval from India's CDSCO panel to conduct Phase III clinical trials for Glycopyrrolate-Indacaterol metered dose inhalation, a maintenance treatment for COPD patients. • The company also secured approval for Phase III trials of Vilanterol-Umeclidinium powder inhalation, with the condition that severe COPD patients with inspiratory flow rates below 30 L/min be excluded. • Both combination therapies target bronchodilation through different mechanisms - LAMA/LABA combinations that improve airflow obstruction in COPD by relaxing bronchial smooth muscles.

GSK's Relvar Ellipta Demonstrates Superior Asthma Control in Landmark Real-World Study

• The Salford Lung Study shows patients using Relvar Ellipta had double the odds of achieving improved asthma control compared to standard care treatments. • The groundbreaking 52-week open-label trial involved 4,233 patients and was designed to reflect real-world clinical practice with minimal exclusion criteria. • Despite promising control outcomes, Relvar Ellipta carries boxed warnings for asthma-related death risk in children and adolescents, limiting its use in these populations.

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HHS Expands Medicare Price Negotiations with 15 New Drugs Including Ozempic and Trelegy Ellipta

• The U.S. Department of Health and Human Services has selected 15 additional drugs for Medicare Part D price negotiations, targeting medications for diabetes, cancer, and asthma that account for $41 billion in Medicare spending. • The selected medications include popular drugs like semaglutide (Ozempic), Trelegy Ellipta, and Xtandi, with negotiations set to begin in 2025 and negotiated prices taking effect in 2027. • This second round of negotiations builds on the success of the first cycle, which achieved significant price reductions ranging from 38% to 79% on ten medications under the Inflation Reduction Act.

Medicare to Negotiate Single Price for Novo's Semaglutide Products Including Ozempic and Wegovy

• Medicare has selected semaglutide as one of 15 drugs for its second round of price negotiations, treating all formulations including Ozempic, Wegovy, and Rybelsus as a single product. • The negotiations will establish a unified "maximum fair price" for all semaglutide products, impacting Novo Nordisk's medications that currently list at $998-$1,349 per month. • CMS's approach focuses on the drug's active moiety rather than individual brand names, aiming to prevent "product hopping" and ensure consistent pricing across different formulations.

Study finds no clinical advantage of budesonide inhaler over fluticasone in COPD

A recent study published in BMJ compared the effectiveness and safety of two single-inhaler triple therapies for COPD, finding that fluticasone-umeclidinium-vilanterol resulted in fewer COPD exacerbations compared to budesonide-glycopyrrolate-formoterol, without increasing the risk of pneumonia.

Circassia Receives FDA Boost for COPD Drugs in the US

UK biotech firm Circassia has received favorable decisions from the FDA for its COPD drugs, Tudorza and Duaklir, marking a significant step in its business recovery. The company faces financial obligations to AstraZeneca due to licensing agreements, amidst a competitive market landscape.

GSK's Nucala (Mepolizumab) Shows Promise in COPD Treatment, Regulatory Submissions Underway

• GSK's Nucala (mepolizumab) demonstrates a clinically meaningful reduction in moderate/severe exacerbations in COPD patients with an eosinophilic phenotype. • The MATINEE Phase III trial supports regulatory submissions for Nucala as an add-on maintenance treatment for COPD, potentially the first monthly biologic for this condition. • Regulatory reviews are underway in both the US (FDA) and China (CNMPA), with the US PDUFA date set for May 7, 2025. • Nucala, already approved for other IL-5 mediated conditions, could offer a targeted therapy for up to 40% of COPD patients with type 2 inflammation.

Dupixent Approved for COPD: A New Era in Targeted Therapy

• The FDA has approved Dupixent (dupilumab) for COPD, marking the first targeted therapy addressing the IL-4 and IL-13 pathways linked to type 2 inflammation. • Clinical trials demonstrated Dupixent reduced moderate-to-severe COPD exacerbations by 30% over 52 weeks, with significant improvements in lung function. • COPD affects approximately 44 million people in the 7MM, with the market expected to reach USD 16 billion in 2023 and grow at a CAGR of 5% by 2034. • Emerging therapies like itepekimab, benralizumab, tezepelumab and mepolizumab are in development, poised to further transform the COPD treatment landscape.
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