The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has approved AstraZeneca's Trixeo Aerosphere (budesonide/glycopyrronium/formoterol fumarate) with a revolutionary next-generation propellant that reduces climate impact by 99.9% compared to conventional inhaler propellants. This milestone makes Trixeo the first pressurized metered-dose inhaler (pMDI) to utilize the near-zero Global Warming Potential (GWP) propellant HFO-1234ze(E).
The fixed-dose triple-combination therapy, already licensed for chronic obstructive pulmonary disease (COPD) treatment in adults, will now deliver the same therapeutic benefits with a significantly reduced environmental footprint. According to clinical data, the new formulation achieves a carbon impact comparable to dry powder inhalers that require no propellant at all.
Clinical Equivalence Maintained
The regulatory approval was based on comprehensive bioequivalence studies comparing Trixeo with the next-generation propellant HFO-1234ze(E) to the current formulation using HFA-134a. Results demonstrated that the new version maintains identical therapeutic efficacy while preserving the established safety and tolerability profile.
"The transition of Trixeo to the propellant with near-zero Global Warming Potential means that healthcare professionals can focus on optimizing outcomes for their COPD patients based on clinical need, while also supporting climate goals," said Professor Omar Usmani of Imperial College London. "Clinicians and their patients shouldn't feel that they have to choose between the most appropriate treatment and the planet."
Addressing a Significant Environmental Challenge
Respiratory inhaled medicines delivered by pMDIs account for 78% of inhaler usage globally and contribute approximately 0.04% of global greenhouse gases. In the UK specifically, pMDIs make up 70% of all inhaled medicines use and represent 3% of the total NHS carbon footprint.
The environmental impact of respiratory care extends beyond just the propellants. Studies indicate that inadequate disease control leading to increased healthcare utilization actually constitutes the largest environmental contribution from respiratory diseases. By maintaining effective symptom management while reducing propellant emissions, the new Trixeo formulation addresses both clinical and environmental concerns.
First Step in Broader Sustainability Initiative
Ruud Dobber, Executive Vice President of AstraZeneca's BioPharmaceuticals Business Unit, described the approval as "a major milestone in AstraZeneca's commitment to transition our pMDI portfolio to the propellant with near-zero Global Warming Potential."
Trixeo is the first in AstraZeneca's portfolio to make this transition, with the company aiming to convert its entire pMDI portfolio to the near-zero GWP propellant by 2030 as part of its Ambition Zero Carbon strategy. The UK rollout of the reformulated Trixeo is expected to begin within months.
Tom Keith-Roach, President of AstraZeneca UK, emphasized the significance of this development: "The UK approval of Trixeo Aerosphere with the near-zero Global Warming Potential propellant marks a world 'first' and an important step in improving the environmental impact of our portfolio of inhaled respiratory medicines to support the NHS in achieving its net zero carbon goals."
Technical Development and Collaboration
The next-generation propellant, HFO-1234ze(E), was developed and patented by Honeywell. AstraZeneca announced its collaboration with Honeywell in 2022 to develop respiratory inhaled medicines using this innovative propellant.
The clinical development program for the new propellant included in vitro testing, in vivo bioequivalence (PK) studies, and safety and efficacy clinical trials. Additional studies are currently underway to assess bioequivalence with AstraZeneca's other pMDI-delivered medicines.
Global Expansion Plans
Beyond the UK, regulatory applications for Trixeo/Breztri with the next-generation propellant are currently under review in Europe, China, and additional countries. The medication, marketed as Breztri Aerosphere in the US, China, and Japan, has already been prescribed to more than five million patients globally.
The reformulated version will maintain the same indication, product strength, and dosage regimen as the current formulation, ensuring continuity of care for patients while delivering significant environmental benefits.
COPD Burden and Treatment Landscape
COPD affects hundreds of millions of people worldwide and remains a leading cause of death globally. The disease is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.
Triple therapy combining an inhaled corticosteroid (ICS), a long-acting muscarinic antagonist (LAMA), and a long-acting β2 agonist (LABA) – as found in Trixeo – is recommended for COPD patients who remain symptomatic despite dual therapy or who are at high risk of exacerbations.
The approval of Trixeo with the next-generation propellant represents a significant advancement in respiratory medicine, demonstrating that effective disease management and environmental responsibility can be achieved simultaneously.
