Clinical Overview: PT027 for Exacerbation Risk Reduction, Improved Lung Function in Asthma

PT027 (albuterol/budesonide) is being developed by AstraZeneca as a potential first-in-class combination of a short acting beta₂-agonist (SABA) and an inhaled corticosteroid (ICS).¹

Several large phase 3 trials have shown promising results in the drug’s ability to reduce the risk of severe exacerbations and improve lung function compared to albuterol as a rescue inhaler. PT027 has also been found effective compared to placebo for the treatment of exercise-induced bronchoconstriction in patients with asthma.^1,2

Mechanism of Action^3,4

PT027 is the combination of the previously approved drugs albuterol and budesonide. Albuterol is a SABA that relaxes smooth muscle on bronchial tissue, whereas budesonide is an ICS that decreases inflammation.

Dosage and Administration^1,5

PT027 was studied at doses of 180/160 micrograms and 180/80 micrograms. Both doses are delivered as 2 actuations of 90/80 micrograms and 90/40 micrograms, respectively.

PT027 is delivered through a single pressurized metered-dose inhaler (pMDI) and was studied for as-needed use in response to asthma symptoms and prevention of exercise-induced bronchospasm.

Adverse Events (AEs)^1,3,4

AstraZeneca reported the safety and tolerability of PT027 as consistent with the safety profiles of each component individually.

The most common AEs reported during budesonide use include respiratory infection, rhinitis, and otitis media. The most common AEs during albuterol use include headache, tachycardia, dizziness, nervousness, tremor, pharyngitis, rhinitis, and upper respiratory tract infections.

Health care providers should counsel patients on proper inhaler technique.

Warnings and Precautions^3,4

Specific warnings and precautions for PT027 have not been established as the MANDALA and DENALI studies have not published official results. It is anticipated that the warnings and precautions will be similar to those of the individual components.

Albuterol may cause paradoxical bronchospasm, cardiovascular effects such as increased pulse or blood pressure, and immediate hypersensitivity reactions. Patients should not exceed the recommended dose of albuterol and watch for deterioration of asthma after use, which may occur over several hours or several days.

Albuterol may also cause significant hypokalemia although this decrease is usually transient. Prescribers should be cautious when prescribing albuterol for patients with cardiovascular disorders, convulsive disorders, diabetes mellitus, or hyperthyroidism.

Budesonide alone is not indicated for the treatment of acute bronchospasm. Hypersensitivity reactions may occur, including anaphylaxis, rash, or angioedema.

Localized infections of the mouth and throat, such as Candida albicans, may occur. Budesonide may cause immunosuppression or worsening of existing infections.

For patients who are transitioning from systemic corticosteroids to inhaled budesonide, impaired adrenal function is a risk necessitating a slow taper. Budesonide may also cause a reduction in bone mineral density and effects on growth in children.

Close monitoring is warranted in patients with glaucoma or cataracts and patients with eosinophilic conditions.

Pregnancy and Lactation^3-6

Women who were pregnant, breast feeding, or planning to become pregnant were excluded from the MANDALA study.

The Global Strategy for Asthma Management and Prevention emphasizes the importance of asthma control in pregnant women and recommends continued use of intranasal corticosteroids and beta₂-agonists. Prescribing information from the individual components of PT027 support continued use of inhaled albuterol and budesonide in pregnancy if needed to control the mother’s asthma.

There are no data on the presence of albuterol or budesonide in human milk. Corticosteroids are known to be secreted in human milk and thus the budesonide package insert warns to take this into consideration when choosing whether to discontinue nursing or use of the medication.

Although data regarding albuterol in human milk are lacking, albuterol’s oral bioavailability is low. As always, prescribers must consider the risks and benefits of medication continuation and of breastfeeding the infant before initiating or continuing therapy.

About the Author

Hannah Monza, PharmD, BCPS, is a clinical pharmacist at MedStar Health.

References

1. Kemp A. Fixed-dose combination of albuterol and budesonide (PT027) demonstrated significant benefits for asthma patients in MANDALA and DENALI Phase III trials. AstraZeneca. September 9, 2021. Accessed March 7, 2022. https://www.astrazeneca.com/media-centre/press-releases/2021/pt027-phiii-asthma-trials-met-primary-endpoints.html
2. LaForce C, et al. Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: The TYREE study. Ann Allergy Asthma Immunol. 2022;128(2):169-177. doi:10.1136/bmjresp-2021-001077
3. Proair HFA [package insert]. Frazer, PA: Teva. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021457s036lbl.pdf. February 2019. Accessed March 11, 2022.
4. Budesonide suspension [package insert]. North Wales, PA: Teva. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2414058b-5d39-42f2-915f-03a5e1101ab5. October 2019. Accessed March 11, 2022.
5. Chipps, BE, et al. Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomized, double-blind, active-controlled MANDALA study. BMJ Open Resp Res. 2021;8:e001077. doi:10.1136/bmjresp-2021-001077
6. Global Initiative for Asthma. Global strategy for asthma management and prevention, 2021. Accessed March 8, 2022. https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf