AstraZeneca Announces Positive Phase III Results for PT027 (Albuterol/Budesonide) in Asthma

Compiled and translated by | Fan Dongdong

Recently, AstraZeneca announced positive results from two Phase III trials of PT027, its fixed-dose combination of albuterol and budesonide, in patients with moderate-to-severe asthma.

PT027, a potential best-in-class inhaled fixed-dose combination co-developed by AstraZeneca and Avillion, primarily consists of the short-acting β2-agonist (SABA) albuterol and the inhaled corticosteroid (ICS) budesonide. This combination therapy is indicated for asthma, a chronic, inflammatory, and fluctuating respiratory disease that affects up to 339 million adults and children worldwide. The company stated that in two Phase III trials, both doses of PT027 (180/160 mcg and 180/80 mcg) met all primary endpoints compared to the individual components of albuterol 180 mcg and budesonide 160 mcg, demonstrating therapeutic benefits for patients with asthma.

The results of the recently announced MANDALA Phase III trial demonstrate that, compared with albuterol, the use of PT027 as a rescue medication for asthma symptoms significantly reduces the risk of severe exacerbations in patients, both statistically and clinically. The trial enrolled 3,132 patients with moderate-to-severe asthma who were receiving maintenance ICS therapy, with or without additional controller medications.

Another Phase III DENALI trial also yielded similarly positive results. The trial enrolled a total of 1,001 patients with mild-to-moderate asthma who had previously been treated with as-needed SABA alone or in combination with low-dose maintenance ICS. The results demonstrated that, compared with albuterol and budesonide administered separately, treatment with PT027 resulted in a statistically significant improvement in lung function as measured by forced expiratory volume in one second (FEV1).

In response, Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated, “All asthma patients face the risk of severe exacerbations, regardless of their disease severity, and it is well known that many patients overuse short-acting bronchodilators. These exciting trial results for PT027 could potentially provide an innovative and best-in-class asthma treatment by preventing exacerbations.” The company noted that the safety and tolerability profile of PT027 in both trials was consistent with the known profiles of its individual components. In a statement, AstraZeneca announced that detailed data from the MANDALA and DENALI trials will be presented at upcoming medical conferences.

While the company has achieved positive developments in the asthma sector, it has faced repeated setbacks in another respiratory disease indication. Since the rollout of the AstraZeneca COVID-19 vaccine in June, over 100 individuals in Taiwan, China have died following vaccination, with the specific causes of death still under investigation. Furthermore, suspected fatalities linked to the administration of the AstraZeneca COVID-19 vaccine have been reported consecutively across numerous countries and regions worldwide, including Norway, Italy, Austria, the United Kingdom, Japan, South Korea, and Australia. Concerns regarding potential safety risks and mortality have also prompted regulatory authorities in multiple countries to suspend or ban the use of AstraZeneca’s vaccine.

In addition to widespread concerns regarding vaccine safety, the company's vaccine procurement agreement with the European Union had also previously been mired in disputes. In August last year, the EU, on behalf of its 27 member states, signed a COVID-19 vaccine procurement agreement with AstraZeneca to purchase 300 million doses of its vaccine. However, during the first quarter of this year, only 30 million doses were successfully delivered out of the 120 million originally stipulated in the agreement. In early September, the EU and AstraZeneca reached a settlement agreement, whereby AstraZeneca committed to delivering 60 million doses by the end of the third quarter of this year, 75 million doses by the end of the fourth quarter, and 65 million doses by the end of the first quarter of 2022.

References:

1.AstraZeneca: MANDALA, DENALI Phase III Trials Of PT027 For Asthma Meet All Primary Goals

2.AZ builds case for fixed-dose albuterol and budesonide combo in asthma