A low-carbon version of a triple combination pressurised metred dose (pMDI) inhaler indicated for adults with moderate-to-severe chronic obstructive pulmonary disease (COPD) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA), its manufacturer AstraZeneca has announced.
The budesonide/glycopyrronium/formoterol fumarate inhaler (brand name Trixeo Aerosphere) currently uses the propellant hydrofluoroalkane-134a (HFA-134a), which is known for its high Global Warming Potential (GWP).
The approved next-generation propellant hydrofluoroolefin-1234ze (HFO-1234ze(E)) is a fluorinated gas with a GWP 99.9% lower than the original propellant.
With this change, the triple combination inhaler achieves a carbon footprint comparable to dry powder inhalers that do not require a propellant.
No changes have been made to the active ingredients, recommended dose or clinical use, the MHRA said.
Commenting on the approval, Dr Omar Usmani, consultant chest physician and clinician scientist at Royal Brompton Hospital in London and professor of respiratory medicine at Imperial College London, said: ‘The transition of Trixeo to the propellant with near-zero Global Warming Potential means that healthcare professionals can focus on optimising outcomes for their COPD patients based on clinical need, while also supporting climate goals.
‘Clinicians and their patients shouldn’t feel that they have to choose between the most appropriate treatment and the planet.’
Bioequivalence, safety and tolerability
The MHRA approval was based on the results from the next-generation propellant clinical development programme, which included one trial focusing on lung exposure bioequivalence and the other focusing on systemic exposure bioequivalence of the low-carbon and original propellants.
In both trials, exposure to each of the triple therapy components met bioequivalence criteria for the near-zero GWP HFO-1234ze propellant relative to HFA-134a, with no new or unexpected safety findings.
There were no reports of serious adverse events or adverse events leading to discontinuation in either trial.
The researchers concluded that the data provided clinical evidence that HFO-1234ze is a viable replacement for HFA-134a.
Low-carbon inhaler transition
Julian Beach, MHRA interim executive director, healthcare quality and access, said: ‘Inhalers are a cornerstone of COPD treatment, helping manage symptoms and prevent exacerbations. However, some inhalers can also contribute to greenhouse gas emissions through their propellants.
‘This approval supports the continued availability of a widely used COPD treatment while enabling a transition to inhalers with a lower carbon footprint – without compromising on safety, quality or clinical benefit.’
In the UK, pMDIs make up 70% of all inhaled medicines use with inhaler emissions representing 3% of the total NHS carbon footprint, according to the charity Asthma + Lung UK.
In 2023, GSK announced its low-carbon salbutamol metered-dose inhaler could reduce greenhouse gas emissions from use of the inhaler by around 90% and phase 3 trials were due to start in 2024.
Research published last year revealed that poorly controlled asthma significantly contributes to greenhouse gas emissions, with these patients contributing eight times more excess GHG than those with well-managed asthma.
The recent UK joint guidelines for chronic asthma highlighted the very high carbon footprints of metred dose inhalers and advocated for the use of dry powder inhalers with a lower carbon footprints and less environmental impact. It also encourages patient education around environmental sustainability and correct disposal of inhalers through the pharmacy.
