Trelegy Ellipta is a once-daily, single inhaler triple therapy from GSK, in collaboration with Innoviva, approved as a long-term maintenance treatment for certain patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
The triple therapy was approved by the U.S. Food and Drug Administration (FDA) on Sept. 18, 2017, based on results showing its effectiveness in Phase 3 clinical trials and other studies. In the European Union, Trelegy Ellipta has been recommended for approval by an arm of the European Medicines Agency, the Committee for Medicinal Products for Human Use (CHMP). A European Commission ruling is expected soon.
Trelegy Ellipta was FDA approved for COPD patients on a fixed-dose fluticasone furoate and vilanterol combination (brand name, Breo Ellipta) for airflow obstruction and flares who want additional help, or for patients already taking umeclidinium plus Breo Ellipta.
How Trelegy Ellipta works
The mechanism of action of Trelegy Ellipta, a dry powder inhalation treatment, is based on how each of its ingredients works.
Fluticasone is a synthetic corticosteroid with anti-inflammatory activities, which reduces theairway swelling seen in COPD. Although the precise mechanism of action of fluticasone is not fully understood, it is thought to have a wide range of actions on different immune cells and cell signaling molecules that are involved in inflammation.
Umeclidinium is a long-acting muscarinic antagonist, also known as an anticholinergic. It binds to the muscarinic receptors and blocks their activity. It has a particularly high affinity for a subtype of muscarinic receptor called the the M3 receptor, located on the muscle of the bronchi and responsible for bronchi constriction. By binding to M3, umeclidinium blocks the activity of the M3 receptor allowing for dilation, or expansion, of the bronchi.
Vilanterol is a long-acting beta2-adrenergic agonist that works by stimulating an enzyme called adenyl cyclase in the smooth muscle cells of the bronchi. This enzyme helps convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which helps bronchial muscle cells to relax.
Trelegy Ellipta in clinical trial
A Phase 3a study (NCT02345161) assessed the efficacy, safety, and tolerability of Trelegy Ellipta in more than 1,800 people with COPD over 24 weeks. It compared the triple combo therapy to the combination of budesonide and formoterol (Symbicort). Statistically significant improvements were seen in those given Trelegy Ellipta compared with people using Symbicort regarding lung function (measured by trough FEV1) and health-related quality of life (measured by the St. George’s Respiratory Questionnaire – SGRQ).
A 52-week Phase 3 study (NCT02164513), called IMPACT, assessed the effectiveness of the triple combination therapy in reducing the annual rate of moderate and severe exacerbations compared with a dual therapy — Breo Ellipta or umeclidinium and vilanterol (brand name, Anoro Ellipta) — in 10, 355 COPD patients. Results, announced in September 2017, showed that Trelegy Ellipta reduced the annual rate of moderate-to-severe exacerbations in treated patients by 15 percent compared with Breo Ellipta, and by 25 percent compared with Anoro Ellipta. Treatment was also seen to significantly improve patients’ lung function and quality of life, and slow disease progression of their disease. [Both Breo Ellipta and Anoro Ellipta are marketed by GSK.]
Additional studies concluded recently, but GSK has not yet released their results:
A 24-week randomized, and double-blind Phase 3b study (NCT02729051) compared Trelegy Ellipta as a single inhaled treatment with an “open” triple therapy in people with COPD. The open therapy consisted of two separate treatments, the combination of fluticasone and vilanterol, plus umeclidinium. Its primary endpoint was a change in lung function as measured by trough FEV1 at 24 weeks. Secondary endpoints included health-related quality of life, time to first moderate or severe exacerbation, transitional dyspnea index, number of participants with adverse events, and number of participants with abnormal blood parameters.
A Phase 4 study (NCT02982187) assessed the benefits of delivering the triple therapy using Ellipta dry-powder inhaler compared to two other types of dry-powder inhalers. This study measured the number of participants who made at least one critical error after reading the patient information leaflet (primary objective) and being instructed by a healthcare provider (secondary objective).
The most common side effects associated with the use of Trelegy Ellipta include headache, back pain, altered taste sensation, cough, throat pain, and gastroenteritis.
Trelegy Ellipta is not indicated to relieve acute bronchospasm, or for the treatment of asthma, as its safety and efficacy in people with asthma have not been established. Long-acting beta2-adrenergic agonist such as vilanterol may increase the risk of asthma-related death.
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