US FDA accepts New Drug Application filed by Avillion for AstraZeneca's PT027 for the as-needed treatment or prevention of symptoms in asthma patients

• Results from Phase III trials conducted by Avillion in over 4,000 patients show that PT027, a novel fixed-dose combination of albuterol and budesonide, significantly reduced the risk of a severe asthma exacerbation compared to albuterol alone
• Avillion announces expansion of partnership with AstraZeneca on PT027 and will fund and execute a new Phase 3b study

LONDON, May 31, 2022 /PRNewswire/ -- Avillion LLP, a drug development company focused on the co-development and financing of pharmaceutical candidates from proof-of-concept through to regulatory approval, announces that the US Food and Drug Administration (FDA) has accepted for filing Avillion's New Drug Application (NDA) for AstraZeneca's PT027. The proposed indication is for the as-needed treatment or prevention of bronchoconstriction and for the prevention of exacerbations in patients with asthma 4 years of age and older.

PT027 is a potential first-in-class inhaled, fixed-dose combination of albuterol, a short-acting beta2-agonist (SABA), and budesonide, an inhaled corticosteroid (ICS), in the US, being developed by Avillion and AstraZeneca under a 2018 clinical co-development agreement.

Under the terms of the agreement, Avillion funded, sponsored, and executed a multicentre, global clinical trial programme for PT027 comprising four studies involving more than 4,000 patients. Avillion also has regulatory responsibility including filing the NDA through to a regulatory decision in the US. Following the successful approval of PT027, AstraZeneca has the option, upon certain financial payments, to commercialise the medicine in the US.

The NDA submission is based on data from studies conducted by AstraZeneca and Avillion to assess the safety and efficacy of PT027. Positive results from the lead Phase III study, MANDALA, were recently published in the New England Journal of Medicine and presented at the American Thoracic Society (ATS) 2022 International Conference (13-18 May 2022). PT027 at two different strengths of budesonide, used as an as-needed rescue medicine, demonstrated a statistically significant reduction in the risk of a severe exacerbation versus albuterol rescue in patients with moderate to severe asthma.^1,2

The co-development partnership between AstraZeneca and Avillion has recently expanded to include the BATURA study, a randomised Phase 3b decentralised trial to further assess the role of PT027 in preventing asthma exacerbations.

Allison Jeynes, MD, Chief Executive Officer of Avillion, said: "Our clinical studies have demonstrated the strong potential of PT027 in providing a meaningful contribution to patient care in asthma, and we're pleased to be making this NDA filing and reaching a key milestone in what continues to be an excellent partnership with AstraZeneca. Throughout our various clinical co-development collaborations, Avillion has maintained a 100% trial success rate across multiple therapy areas, and the evolution of our model to include regulatory filing responsibilities further demonstrates the strong value we can provide to partner companies. We're excited to continue working with AstraZeneca as PT027 progresses through the regulatory process, and as we prepare to launch the BATURA study as part of an expansion to the partnership."

Notes

Asthma

Asthma is a chronic, inflammatory, variable respiratory disease that affects as many as 339 million adults and children worldwide,³ including over 25 million in the US.⁴

Patients with asthma experience recurrent breathlessness and wheezing, which varies over time, and in severity and frequency.⁵ These patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.^6,7

There are an estimated 176 million asthma exacerbations globally per year,⁸ including more than 10 million in the US;⁴ these are physically threatening and emotionally significant for many patients⁹ and can be fatal.^3,10

Inflammation is central to both asthma symptoms⁵ and exacerbations.¹¹ Many patients experiencing asthma symptoms use a SABA as a rescue medicine, however, taking a SABA alone does not address inflammation, leaving patients at risk of severe exacerbations,¹² which can result in impaired quality of life,¹³ hospitalisation¹⁴ and frequent oral corticosteroid (OCS) use.¹³ Treatment of exacerbations with as few as 1-2 short courses of OCS are associated with an increased risk of adverse health conditions including type 2 diabetes, depression/ anxiety, renal impairment, cataracts, cardiovascular disease, pneumonia and fracture.^5,15,16 International recommendations from the Global Initiative for Asthma no longer recommend SABA alone as the preferred rescue therapy.⁵

About Avillion

Avillion offers pharma partners an innovative model providing additional funding and clinical development expertise, to maximise the potential of new and existing assets. With deal sizes ranging from $50M–$600M, Avillion takes on the full clinical and regulatory risk, focusing on the speed and quality of trial execution. Typically supporting programs post proof-of-concept through to registration and with an agnostic approach to therapy area, Avillion prides itself in adding value around operational expertise while being backed by established long-term investors.

Avillion was founded in 2012 and is backed by Abingworth and Blackstone Life Sciences (previously Clarus Ventures). The PT027 clinical co-development programme was funded by Blackstone Life Sciences, Royalty Pharma and Abingworth.

For more information, please visit us at www.avillionllp.com

References

1. Papi A, et al. Albuterol-budesonide fixed-dose combination rescue inhaler for asthma. N Eng J Med. 2022; May 15. DOI: 10.1056/NEJMoa2203163. Online ahead of print

2. Papi A, et al. Efficacy and safety of as-needed albuterol/budesonide versus as-needed albuterol in adults, adolescents and children aged ≥4 years with moderate-to-severe asthma: Results of the MANDALA study. American Thoracic Society International Conference 2022. Oral Presentation.

3. Chipps BE, et al. Efficacy and safety of albuterol/budesonide (PT027) in mild-to-moderate asthma: Results of the DENALI study. American Thoracic Society International Conference 2022. Abstract. Available at: https://www.abstractsonline.com/pp8/#!/10476/presentation/7832 [Last accessed 15 May 2022].

4. The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://www.globalasthmareport.org/Global%20Asthma%20Report%202018.pdf. [Last accessed: 4 May 2022].

5. CDC. Most Recent National Asthma Data. [Online]/ Available at: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. [Last accessed: 4 May 2022].

6. Global Initiative for Asthma. 2021 GINA Report, Global Strategy for Asthma Management and Prevention. [Online]. Available at: https://ginasthma.org/wp-content/uploads/2021/04/GINA-2021-Main-Report_FINAL_21_04_28-WMS.pdf [Last accessed: 4 May 2022]

7. Price D, et al. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 24: 14009.

8. Papi A, et al. Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate-to-severe asthma. J Allergy Clin Immunol Pract. 2018; 6 (6): 1989-98.e3.

9. Sastre J, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organ J. 2016; 9: 13.

10. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372

11. Wark PA, et al. Asthma exacerbations· 3: pathogenesis. Thorax. 2006; 61 (10): 909-15.

12. Nwaru BI, et al. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020; 55 (4): 1901872.

13. Lloyd A, et al. The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK. Prim Care Respir J. 2007; 16 (1): 22-7.

14. Bourdin A, et al. ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions. Eur Respir J. 2019; 54 (3): 1900900.

15. Price DB, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018; 11: 193–204.

16. EPR-3: Expert panel report 3. Guidelines for the Diagnosis and Management of Asthma 2007 (EPR-3). [Online]. Available at: https://www.nhlbi.nih.gov/health-topics/guidelines-for-diagnosis-management-of-asthma. [Last accessed: 4 May 2022].