The COPD and Asthma Drug Fluticasone Furoate, Umeclidinium and Vilanterol (TRELEGY ELLIPTA)

Fluticasone furoate, umeclidinium and vilanterol (TRELEGY ELLIPTA) is a once-daily, fixed-dose, dry-powder inhaler containing drugs from three classes: fluticasone furoate, an inhaled corticosteroid (ICS); umeclidinium, a long-acting muscarinic antagonist (LAMA); and vilanterol, a long-acting beta agonist (LABA).[1] This combination drug was first approved by the Food and Drug Administration in 2017 as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD).

In 2020 the triple-ingredient inhaler received supplemental approval as a maintenance treatment for asthma in patients aged 18 years and older.[2] It is available as a low-dose (100 micrograms [mcg] ICS, 62.5 mcg LAMA, 25 mcg LABA) or high-dose (200 mcg ICS, 62.5 mcg LAMA, 25 mcg LABA) inhaler.

One Trelegy Ellipita inhaler, which lasts approximately one month, costs about $658; it is one of 15 drugs in the current round of price negotiations by the Centers for Medicare and Medicaid Services. The negotiated prices will go into effect in 2027.

The advantage of a triple-ingredient inhaler is convenience; three drugs can be administered in a single inhaler. An important caveat is that many of the studies supporting the benefits of Trelegy Ellipta were funded by its manufacturer.

The FDA has approved a similar triple-ingredient inhaler, with ICS, LAMA and LABA components, for the maintenance treatment of COPD: BREZTRI AEROSPHERE. This inhaler is not approved for asthma.

Components of Trelegy Ellipta are associated with serious adverse events, including increased risks of Candida albicans infections in the mouth and phalanx, glaucoma and cataracts, and worsening of existing infections. Treatment with the triple combination product can also lead to clinically significant cardiovascular effects in some patients, including increased blood pressure and cardiac arrhythmias.

Although Trelegy Ellipta is approved broadly for the maintenance treatment of COPD, it should only be considered for patients for whom COPD exacerbations are no longer adequately controlled with dual therapy, such as with an ICS and a LABA.[3],[4] In such patients, treatment with a triple-ingredient inhaler can be beneficial for lung function and quality of life. For this reason, Public Citizen’s Health Research Group has designated Trelegy Ellipta as Limited Use in patients with severe COPD and inadequately controlled exacerbations on dual-ingredient inhaler therapy.

The therapeutic benefit of Trelegy Ellipta as a maintenance treatment for asthma as well as its long-term safety for this indication have not been adequately demonstrated, as discussed in more detail below.[5],[6] We have therefore designated Trelegy Ellipta as Do Not Use for Seven Years for the maintenance treatment of asthma.

Trelegy Ellipta for maintenance treatment of COPD

All three drug classes of the triple-ingredient inhalers are approved for the treatment of COPD, either as a component of a dual-combination product or as monotherapy. For the approval of Trelegy Ellipta for COPD, its efficacy and safety were assessed in three trials.[7] Two of the trials were 12-week randomized, double-blind trials. Both trials, each including 619 participants, found that the lung function in adult participants with COPD treated with fluticasone furoate/vilanterol as well as umeclidinium was significantly increased compared with those who received fluticasone furoate/vilanterol and placebo.

The third trial, a randomized, double-blind trial with a duration of 52 weeks and 10,355 participants, found that those treated with the components of Trelegy Ellipta had significant improvements in lung function, significantly greater health-related quality of life, and significantly reduced annual rates of moderate or severe exacerbations than participants who received only two components (either fluticasone furoate/vilanterol or umeclidinium/vilanterol). However, treatment with all three components of Trelegy Ellipta did not significantly reduce the annual rate of severe exacerbations compared with treatment with only fluticasone furoate/vilanterol.

The two 12-week trials also found that the rate of adverse events, such as headaches, cough, and diarrhea, was comparable between groups, though slightly more common with the addition of umeclidinium than treatment with only fluticasone furoate/vilanterol.[8] The 52-week safety trial showed that additional adverse events, including infections (such as upper respiratory tract infections, pneumonia, bronchitis, influenza or urinary tract infections), oral candidiasis, joint pain or constipation, occurred among participants receiving the triple-ingredient inhaler. However, deaths during the treatment period due to a cardiovascular event occurred at a lower rate for those who received Trelegy Ellipta (0.54 per 100 patient-years) than for those in the fluticasone furoate/vilanterol arm (0.78) or the umeclidinium/vilanterol arm (0.94).

Unfortunately there are no adequate data from randomized controlled trials comparing the effectiveness and safety of different ICS/LABA/LAMA combinations for the treatment of COPD with each other.[9] A meta-analysis including data from 21,809 COPD patients found no significant differences across such triple-combination COPD treatments for efficacy (such as risk of exacerbation) or safety outcomes (including pneumonia, serious cardiovascular adverse events, or all-cause mortality), although the researchers concluded that Trelegy Ellipta had the greatest efficacy profile amongst triple inhalers approved in the United States.[10]

Moreover, two retrospective observational studies based on U.S. insurance claims data found that adult COPD patients who started treatment with Trelegy Ellipta had lower rates of moderate or severe exacerbations than did patients who started treatment with another triple inhaler, the twice-daily combination of budesonide, glycopyrrolate and formoterol fumarate marketed as Breztri Aerosphere.[11],[12] One of these studies, which was funded by the manufacturer of Trelegy Ellipta, also found that patients on Trelegy Ellipta had a significantly lower risk of all-cause mortality than did those treated with Breztri Aerosphere.[13]

Trelegy Ellipta for maintenance treatment of asthma

The approval of Trelegy Ellipta for the treatment of asthma was based on one randomized, double-blind trial of 2,436 adult participants whose asthma was inadequately controlled with an ICS/LABA combination treatment.[14] The trial, which lasted 24 to 52 weeks, showed that treatment with the triple inhaler product led to statistically significant improvements in lung function compared with treatment only with fluticasone furoate/vilanterol. Health-related quality-of-life data also favored Trelegy Ellipta; however, the average rate of exacerbations a year (0.31) was the same for participants on either a triple or dual combination product.

Adverse events were comparable between the triple-ingredient inhaler and fluticasone furoate/vilanterol.[15] For example, 5% of participants receiving high-dose and 9% receiving low-dose Trelegy Ellipta reported headaches, compared with 6% and 7%, respectively, in those treated with high- and low-dose fluticasone furoate/vilanterol. Among the most common adverse events were infections (such as nasopharyngitis, bronchitis, [viral] respiratory tract infections, sinusitis, rhinitis, urinary tract infections or influenza) and back pain.

The therapeutic benefit of Trelegy Ellipta for asthma compared with both dual-ingredient inhalers[16] and other triple-ingredient inhalers has not been established.[17] For example, several studies show that although treatment with Trelegy Ellipta led to some improvement in asthma control, not all of these improvements were significant or clinically meaningful.[18] Importantly, treatment with Trelegy Ellipta did not consistently lead to significant differences in asthma-related quality of life or asthma control.

For example, a double-blind, randomized study, funded by the manufacturer of Trelegy Ellipta, which included 2,439 participants, found that the addition of umeclidinium to treatment only with fluticasone furoate/vilanterol improved lung function in patients with asthma but did not lead to significant reductions in moderate or severe exacerbations.[19] Similarly, an unblinded trial of only 35 participants showed that switching from treatment with an ICS and a LABA to Trelegy Ellipta had mixed results.[20] Importantly, 35% of patients who had switched to high-dose Trelegy Ellipta continued to have poor asthma symptom control.

Additionally, although one of the touted advantages of a single combined inhaler is its convenience, another study funded by the manufacturer of Trelegy Ellipta found that only 26% of patients persisted with treatment with the single inhaler after one year, compared with 15% of those who used multiple inhalers for triple-drug therapy.[21]

What You Can Do

Public Citizen’s Health Research Group recommends that you only consider Trelegy Ellipta as a maintenance treatment for COPD if your symptoms are not adequately controlled with dual treatment, such as a combination of an ICS and a LABA. For the maintenance treatment of asthma, however, we recommend that you do not use Trelegy Ellipta until its benefit and long-term safety have been established.

Do not change the dose or stop taking Trelegy Ellipta or any other COPD or asthma medication without consulting your clinician first.
 

References

[1] Food and Drug Administration. Clinical review for application number 209482Orig1s000. Trelegy Ellipta. August 24, 2017. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209482Orig1s000MedR.pdf. Accessed April 2, 2025.

[2] GlaxoSmithKline. Label: fluticasone furoate, umeclidinium, and vilanterol (Trelegy Ellipta). June 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209482s018lbl.pdf. Accessed April 2, 2025.

[3] Mannino D, Weng S, Germain G, et al. Comparative effectiveness of fluticasone furoate/umeclidinium/vilanterol and budesonide/glycopyrrolate/formoterol fumarate among US patients with chronic obstructive pulmonary disease. Adv Ther. 2025 Feb;42(2):1131-1146.

[4] Rogliani P, Ora J, Cavalli F, et al. Comparing the efficacy and safety profile of triple fixed-dose combinations in COPD: A meta-analysis and IBiS score. J Clin Med. 2022 Aug 1;11(15):4491.

[5] Kim LHY, Saleh C, Whalen-Browne A, et al. Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: A systematic review and meta-analysis. JAMA. 2021 Jun 22;325(24):2466-2479.

[6] Braido F, Vlachaki I, Nikolaidis GF, et al. Single inhaler with beclometasone, formoterol, and glycopyrronium versus triple therapies in adults with uncontrolled asthma: a systematic review and meta-analysis. Sci Rep. 2025 Feb 4;15(1):4191.

[7] GlaxoSmithKline. Label: fluticasone furoate, umeclidinium, and vilanterol (Trelegy Ellipta). June 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209482s018lbl.pdf. Accessed April 9, 2025.

[8] Ibid.

[9] Rogliani P, Ora J, Cavalli F, et al. Comparing the efficacy and safety profile of triple fixed-dose combinations in COPD: A meta-analysis and IBiS score. J Clin Med. 2022 Aug 1;11(15):4491.

[10] Ibid.

[11] Feldman WB, Suissa S, Kesselheim AS, et al. Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study. BMJ. 2024 Dec 30;387:e080409.

[12] Mannino D, Weng S, Germain G, et al. Comparative effectiveness of fluticasone furoate/umeclidinium/vilanterol and budesonide/glycopyrrolate/formoterol fumarate among US patients with chronic obstructive pulmonary disease. Adv Ther. 2025 Feb;42(2):1131-1146.

[13] Ibid.

[14] GlaxoSmithKline. Label: fluticasone furoate, umeclidinium, and vilanterol (Trelegy Ellipta). June 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209482s018lbl.pdf. Accessed April 9, 2025.

[15] Ibid.

[16] Kim LHY, Saleh C, Whalen-Browne A, et al. Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: A systematic review and meta-analysis. JAMA. 2021 Jun 22;325(24):2466-2479

[17] Braido F, Vlachaki I, Nikolaidis GF, et al. Single inhaler with beclometasone, formoterol, and glycopyrronium versus triple therapies in adults with uncontrolled asthma: a systematic review and meta-analysis. Sci Rep. 2025 Feb 4;15(1):4191.

[18] Agusti A, Fabbri L, Lahousse L, et al. Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications. Allergy. 2022 Apr;77(4):1105-1113.

[19] Lee LA, Bailes Z, Barnes N, et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir Med. 2021 Jan;9(1):69-84

[20] Kushima Y, Shimizu Y, Arai R, et al. Real-life effectiveness of once-daily single-inhaler triple therapy (FF-UMEC-VI) after switching from dual therapy (ICS-LABA) in patients with symptomatic asthma: Trelegy Ellipta for Real Asthma Control Study (T-RECS). Front Allergy;6:1537501.

[21] Busse WW, Abbott CB, Germain G, et al. Adherence and persistence to single-inhaler versus multiple-inhaler triple therapy for asthma management. J Allergy Clin Immunol Pract. 2022 Nov 1;10(11):2904-2913.