Impact case study database

Context

COPD is the third leading cause of death worldwide with almost 4,000,000 patients dying each year globally. In the UK, approximately 1,200,000 patients are living with COPD, with >100,000 emergency NHS admissions and >100,000 patients diagnosed each year, the burden is substantial. More effective, simpler to use treatments are needed to improve patient adherence to treatment routines and reduce the risk of exacerbations that can impair quality of life, lead to hospitalisation or death.

Pathways to impact

Establishing excellent trial facilities - Singh is the Medical Director of the charity-owned dedicated respiratory clinical trial unit, Medicines Evaluation Unit (MEU, located on the grounds of Wythenshawe Hospital in Manchester) (36 beds, employs >100 people).

Committee membership - Vestbo and Singh sit on the GOLD Science Committee. GOLD works with healthcare professionals and public health officials worldwide to improve treatments of COPD.

Reach and significance of the impact

More effective and simpler treatments available for COPD patients

Aclidinium bromide /formoterol fumarate (Duaklir Genuair) received European EMA approval to treat COPD in December 2014 [Ai,1]. It was approved by US FDA in April 2019 (Duaklir Pressair) [Aii,1]. At the time, it was the only twice daily LAMA/LABA in the US, which included COPD exacerbation data in its prescribing information [Aii].

In July 2017, Chiesi’s Trimbow was the first fixed-dose triple combination inhaler for COPD treatment approved in Europe [Bi,3,4]. In March 2019, EMA expanded the label as a treatment for patients with moderate to severe COPD not adequately treated with long acting dual bronchodilation [Bii,5].

Both products are simpler to use than traditional separate inhalers. Chiesi confirmed, COPD “ requires patients to be treated with many drugs that, to date, have to be taken through two or even three inhalers. The possibility of taking all drugs needed by using only one inhaler considerably simplifies the treatment of patients, decreasing the burden on patients and may improve adherence” [Biii]. Improved adherence improves clinical outcomes, including exacerbations, which impair quality of life, lead to hospitalisation or death.

Commercial and industrial Impacts

AstraZeneca reported European sales of USD26,000,000 in 2015 following EMA authorisation of Duaklir Genuair. From 2016, it was available in 25 countries across Europe, Asia and Latin America [Ci]. By 2018, European sales had risen to USD91,000,000 [Cii].

Chiesi said of its Trimbow collaboration, UoM “ has been and remains fundamental to the success of these product developments in providing world-leading expertise in shaping the clinical studies, leading their execution and in the intelligent interpretation of their findings.” [D]. In 2018 Trimbow generated sales of EUR40,000,000 and was commercially available in 19 European countries, as at 31 December 2018 [Ei]. Following the label expansion based on TRIBUTE [5], Trimbow sales in 2019 totalled EUR127,000,000 [Eii].

Impact on UK guidelines

In December 2018, NICE updated guidelines for COPD diagnosis and management. NICE stated “ The evidence showed that, compared with other dual therapy combinations and with monotherapy, LAMA+LABA provides the greatest benefit to overall quality of life, is better than other inhaled treatments for many individual outcomes… is the most cost-effective option” and “ minimising the number and types of inhalers prescribed will make it easier for people to use their inhalers correctly” [Fi]. ACLIFORM was part of the evidence reviewed [Fii,1].

In July 2019, NICE recommended triple therapy as an option for some patients, noting, “ from the economic evidence, using a single inhaler device was more cost effective” [Fi,3,5]. TRILOGY and TRIBUTE provided clinical evidence [Fiii].

Impact on global guidelines

GOLD’s 2020 strategy report confirmed “ Combination treatment… reduces symptoms compared to monotherapy” and “ reduces exacerbations compared to monotherapy”. GOLD cited ACLIFORM [Gi, 1]. GOLD stated triple therapy “ may improve lung function, patient reported outcomes and prevent exacerbations.” [Gi,2,3].

GOLD’s Executive Director confirmed, “ In a 9-month period in 2019, the GOLD website recorded 337,711 hits from 211 countries (28,902 from the UK…), the most recent GOLD strategy document was downloaded 238,536 times demonstrating the reach of our documents and the research cited within them. University of Manchester research on dual and triple inhalers has been critical in progressing the treatment of COPD to more effective and simpler to use inhalers, marking an important change and benefit for COPD patients… The work of Singh and Vestbo on inhaled treatments were important factors in our 2017 and 2019 major revisions, and the updated 2020 guidance” [H].

Australian and New Zealand Guidelines for COPD 2020 (COPD-X Plan), noted that Genuair was one of four LAMA/LABA devices available in Australia, citing ACLIFORM as one of two trials for this treatment [Gii,1]. Regarding triple therapy, it stated “ triple therapy results in a lower rate of moderate or severe COPD exacerbations, and better lung function” and “ Triple therapy delivered in a single inhaler is convenient for patients and may improve adherence” [Gii,3,4,5].

Increasing triple therapy options for patients

As a result of the IMPACT trial, both FDA (April 18) and EMA (November 18) expanded their authorisations for the triple inhaler Trelegy Ellipta, to include a broader population of COPD patients [Ii, Iii, 6]. In EU, it was the first single inhaler triple therapy to be specifically indicated for COPD patients, not adequately treated with dual bronchodilation [Iii]. Trelegy was the first triple inhaler administered by dry powder inhaler, benefiting patients who use this type of inhaler more effectively. In 2018, the product was launched in 26 countries [Ji], increasing to 40 in 2019 [Jii]. GSK reported sales of GBP156,000,000 in 2018 [Ji], rising to GBP518,000,000 in 2019 [Jii]. In July 2020, AstraZeneca’s Breztri Aerosphere was approved by FDA based on the results of ETHOS, thereby bringing a new product to US patients, offering them broader treatment options [Iiii].