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39335111000001107

New Medicines

Trixeo Aerosphere [UK/EU]; Breztri Aerosphere [US] Chronic obstructive pulmonary disease (COPD)

Information

Trixeo Aerosphere [UK/EU]; Breztri Aerosphere [US]
New formulation
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Approved (Licensed)
Launched
February 2021
Feb 21Launched in the US [21]
Feb 21Launched in UK. Price 1 x 120 dose = £44.50 [20].
Dec 20Approved in EU [19]
Oct 20Recommended for EU approval by CHMP - the full indication is "as a maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid and a long‑acting beta2‑agonist or combination of a long-acting beta2‑agonist and a long‑acting muscarinic antagonist (for effects on symptoms control and prevention of exacerbations see section 5.1)" [18].
Jul 20Breztri Aerosphere (the US tradename for this product) has been approved in the US for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) [17].
Oct 19The US FDA rejected inhaled Breztri Aerosphere, the application for which was supported by the PIII KRONOS trial. Details of the FDA´s complete response letter are not available but Astra Zeneca have indicated that they will work closely with the FDA regarding the next steps. That will likely include submission of data from the PIII ETHOS trial, which had not been completed at the time the NDA was submitted.[13]
Sep 19Filings expected to be accepted H2 18 [5].
Mar 19AstraZeneca reported acceptance of a NDA and a MAA by the US FDA and the EMA, for Breztri Aerosphere to treat COPD. [12]
Dec 18EU & US filings now expected to be accepted H2 19 [9].
Feb 18US & EU filings expected 2019 [4].
Dec 15US & EU filings expected 2018 [1].

Category

Inhaled combination of a corticosteroid, long-acting beta-2 agonist and a long-acting muscarinic antagonist, using Aerosphere Delivery Technology, in a pressurised metered-dose inhaler.
About 1.2 million people are affected by COPD in the UK. There are 115,000 new diagnoses a year. However, 60-85% of patients, mainly with mild-to-moderate disease, are thought to remain undiagnosed [14].
Chronic obstructive pulmonary disease (COPD)
Inhalation

Trial or other data

Jun 20PIII ETHOS study is published; the RCT (n=8509) found triple therapy with twice-daily budesonide (at 160 or 320μg dose), glycopyrrolate, and formoterol resulted in lower annual rate of moderate/severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol (1.07, 1.08, 1.42 & 1.24, respectively) [16].
Sep 19Primary outcomes met in PIII (NCT02536508) study [15].
Aug 19PIII ETHOS trial meets primary endpoint. Rate of moderate or severe exacerbations were severely reduced in patients with moderate to very severe COPD treated with Breztri Aerosphere vs dual-combination therapy (glycopyrronium/formoterol fumarate 14.4/9.6mcg; and budesonide/formoterol fumarate 320/9.6mcg) [11].
Sep 18Last pt commences dosing in PIII ETHOS study (NCT02465567) [8].
Sep 18The Lancet Respiratory Medicine publishes results from the PIII KRONOS trial (NCT02497001).[6]
Mar 18Positive top-line results posted from the PIII KRONOS trial (NCT02497001). PT010 (budesonide/formoterol/glycopyrrolate) demonstrated a statistically significant improvement compared with dual combination therapies (formoterol/glycopyrrolate and budesonide/formoterol) in six out of seven lung function primary endpoints based on FEV1 assessments in patients with moderate to very severe COPD. In total, eight of the nine primary endpoints in the trial were met. There were no unexpected safety or tolerability signals for PT010 identified in the trial [3].
Mar 17Data from PIII study (NCT02536508) expected H2 17 [2].
Dec 15PIII study begins [1].
Aug 15Pearl Therapeutics initiates a PIII trial to evaluate safety and tolerability of formoterol/glycopyrrolate, budesonide/formoterol/glycopyrrolate and budesonide/formoterol metered dose inhalation in patients with moderate to severe chronic COPD (PT010008; NCT02536508). The trial will evaluate bone mineral density and visual impairment measured as Lens Opacities Classification System III (LOCS III) Posterior sub capsular (P) Score as the primary endpoints at the end of 52 weeks. The trial will enrol approximately 500 patients between 40 and 80 years of age in the US [2].
Aug 15A PIII trial designed to assess safety and efficacy of budesonide/formoterol/glycopyrrolate, formoterol/glycopyrrolate and budesonide/formoterol is patients with COPD is planned (PT010006; NCT02497001). Change from baseline in morning pre-dose trough forced expiratory volume in 1 second is the defined primary endpoint of the trial. The randomised, double-blind trial is intended to enrol approximately 1,800 patients in the US [2].
Jun 15Pearl Therapeutics initiates a PIII trial to assess efficacy and safety of budesonide/formoterol/glycopyrrolate relative to formoterol/glycopyrrolate and budesonide/formoterol on COPD exacerbation over a 52-week treatment period in patients with moderate to very severe COPD (PT010005; NCT02465567). The trial will enrol approximately 8 000 patients between 40 to 80 years of age in the US [2].

Evidence based evaluations

Trixeo Aerosphere [UK/EU]; Breztri Aerosphere [US] Severe asthma

Information

Trixeo Aerosphere [UK/EU]; Breztri Aerosphere [US]
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Inhaled combination of a corticosteroid, long-acting beta-2 agonist and a long-acting muscarinic antagonist, using Aerosphere Delivery Technology, in a pressurised metered-dose inhaler
1 December 2021At least 1 in 10 children and 1 in 20 adults have asthma [5].
Severe asthma
Inhalation