According to AstraZeneca, the Medicines and Healthcare Products Regulatory Agency(MHRA) has approved a low-carbon version of a triple combination pressurised metred dose (pMDI) inhaler designed for adults with moderate-to-severe chronic obstructive pulmonary disease (COPD).
The propellant hydrofluoroalkane-134a (HFA-134a), which has a high Global Warming Potential (GWP), is currently used in the budesonide/glycopyrronium/formoterol fumarate inhaler (marketed under the Trixeo Aerosphere brand).
With a GWP 99.9% lower than the original propellant, the authorised next-generation propellant hydrofluoroolefin-1234ze (HFO-1234ze(E)) is a fluorinated gas.
By making this modification, the triple combination inhaler’s carbon footprint is on par with that of propellant-free dry powder low-Carbon inhalers.
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.
Bioequivalence, safety and tolerability
The outcomes of the next-generation propellant clinical development program, which comprised two trials focussing on the systemic exposure bioequivalence and lung exposure bioequivalence of the original and low-carbon propellants, were the basis for the MHRA approval.
There were no unexpected or novel safety findings in either trial, and exposure to each of the triple treatment components satisfied bioequivalence requirements for the nearly zero GWP HFO-1234ze propellant in comparison to HFA-134a.
In neither trial were there any reports of severe adverse events or adverse events that resulted in termination.
The data, according to the researchers, showed that HFO-1234ze is a good substitute 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.’
According to the organisation Asthma + Lung UK, pMDIs account for 70% of all inhaled medication use in the UK, and inhaler emissions account for 3% of the NHS’s overall carbon footprint.
GSK stated in 2023 that phase 3 trials of their low-carbon salbutamol metered-dose inhaler were scheduled to begin in 2024 and that it might cut greenhouse gas emissions from inhaler use by about 90%.
Asthma patients with poorly managed asthma create eight times more excess greenhouse gas emissions than those with well-managed asthma, according to research released last year.
The use of dry powder low-carbon inhalers with a reduced carbon footprint and less environmental impact was recommended by the recent UK joint guidelines for chronic asthma, which emphasised the extremely large carbon footprints of metred dose inhalers. Additionally, it promotes patient education through the pharmacy regarding proper inhaler disposal and environmental sustainability.
