On 28 August, AstraZeneca announced positive results from the Phase III ETHOS trial for its triple-combination therapy inhaler Breztri Aerosphere (budesonide/ glycopyrronium/ formoterol fumarate) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).
The ETHOS trial builds on the promising data verified in the KRONOS trial, which helped Breztri Aerosphere gain its first approval by the Japanese Ministry of Health, Labor and Welfare in June 2019. Following these encouraging results, GlobalData anticipates a rapid approval for the drug in the EU and US, which will strengthen AstraZeneca’s position as a leading player in the COPD market.
In the ETHOS study, Breztri demonstrated a statistically significant reduction in the rate of moderate to severe exacerbations when compared with AstraZeneca’s dual-combination therapies Bevespi Aerosphere (glycopyrronium/ formoterol fumarate) and PT009 (budesonide/ formoterol fumarate). Single-inhaler triple-combination therapy is an emerging treatment option that is reserved for COPD patients who have experienced more than two exacerbations and/or one hospitalisation in the previous year.
The use of triple-combination therapy is proven to improve lung function and symptoms, as well as reduce exacerbations compared to inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), or LAMA monotherapy. This was demonstrated in the KRONOS trial where Breztri showed a 52% reduction in the rate of moderate-severe exacerbations when compared with Bevespi. Additionally, patients who also present with asthmatic features such as elevated blood eosinophils are potential candidates for this therapy.
The Global Institute of chronic Obstructive Lung Disease (GOLD) has acknowledged the relationship between blood eosinophils and ICS benefit, signifying its role as a biomarker that can be used to differentiate between stable and exacerbating COPD. GOLD guidelines suggest that blood eosinophil counts will influence the course of adjuvant ICS therapy, giving clinicians additional diagnostic measures to optimize treatment and deliver a more personalised and targeted approach.
Although this creates a niche for triple-combination therapy, experts note that this is the first time a fixed-dose triple-combination therapy has shown benefit at two inhaled corticosteroid doses, which has the advantage of allowing physicians to tailor the dosage to individual patients. This advances the objective of personalised COPD care, giving Breztri a slight edge over existing triple-combination inhalers.
AstraZeneca is playing a two-year catch-up with GlaxoSmithKline’s (GSK’s) Trelegy Ellipta (fluticasone furoate/umeclidinium bromide/vilanterol trifenatate). However, its predecessor, AstraZeneca’s Symbicort (budesonide/formoterol fumarate), has seen strong use since its launch in 2003, and prescriber familiarity with the drug will help drive significant Breztri uptake. Furthermore, Symbicort has continued to achieve greater sales than GSK’s Relvar Ellipa (fluticasone furoate/vilanterol trifenatate), potentially signalling a positive future for Breztri in the triple-combination field. Key opinion leaders (KOLs) interviewed by GlobalData have indicated that physicians were keen to switch patients currently receiving ICS/LABA and LAMA in separate devices to ICS/LABA/LAMA to improve overall adherence. Familiarity with Symbicort’s prescribing patterns will add momentum to Breztri’s market access strategy.
Following US and EU approval, Breztri will benefit from AstraZeneca’s extensive marketing experience to help catapult sales and overcome its late market entry. Based on the combination of promising trial data, variable dosing, and delivery with Aerosphere Delivery Technology, GlobalData believes that Breztri will reach blockbuster levels of sales over the next decade, supported by swift uptake.
GlobalData (2019) Expert Insight: US Sees Increase in Severe Pulmonary Disease, Likely Linked to E-Cigarette Use, August 2019, GDHC2620EI
GlobalData (2017) PharmaPoint: Chronic Obstructive Pulmonary Disease – Global Drug Forecast and Market Analysis to 2025, GDHC145PIDR