With over 7000 medicines in development, new treatments will continue to change patients’ lives; slowing disease progression, avoiding illness and reducing overall costs for healthcare systems. But developing a new medicines is a long, complex and risky process with no guarantees of success. Over the coming weeks we look at number of new medicines and role pharmaceutical incentives or IP has played in their development.

Around 358 million people in the world suffer from asthma and every year 400,000 patients die from asthma[1]. 384 million people live with Chronic Obstructive Pulmonary Disease (COPD) worldwide with a global prevalence of 11.7%[2]. In 2010, COPD alone was estimated to have cost the global economy $2.1 trillion and it is estimated that this could rise to $4.8trillion by 2030. Much of this cost is associated with the result of sub-optimal management, which can lead to exacerbations, hospitalisations and reduced productivity. 

There is notably a clear and well-established link between non-adherence to asthma and COPD treatment and increased morbidity, mortality, rising healthcare costs, as well as the clinical and economic consequences.[3,4] Therefore, it is in the patients’ and systems’ interests to find a medication that could more easily be adhered to and used correctly, with fewer errors, with a view to achieving better outcomes. However, moving from twice-daily medication, as per current standard of care, to once-daily with a 24-hour duration of action in an easy to use device with fewer errors, while balancing the safety profile was a real challenge which required considerable investment in R&D. 

Relvar Ellipta was approved in 2013, and is designed to treat asthma and COPD. GSK’s Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate (FF), an inhaled corticosteroid, and vilanterol (VI), a long-acting beta2-agonist, in a single inhaler. It is given by inhalation and only needs to be taken once a day to gain sustained 24-hour control. It is hoped this will be more convenient for patients and help them adhere to their medicine.

In addition to the randomised controlled clinical trials conducted to support the regulatory filing for marketing authorisation, we tested the medicine in a real-world setting, starting when it was an investigational medicine, up until 2016 [post authorisation]. We conducted the world’s first large-scale clinical research in an everyday clinical practice. Effectiveness studies examine interventions under circumstances that more closely approach real-world practice, with more heterogeneous patient populations, less-standardised treatment protocols, and delivery in routine clinical settings. In that context, the Salford Lung Studies (SLS) were ‘real world’ effectiveness studies designed to test the hypothesis that the once-daily properties of Relvar Ellipta may confer benefits compared with usual care. Generating these data will enable clinical decision makers to better evaluate a drug's effectiveness in the broader population in which it will be prescribed in clinical practice, and therefore determine its clinical value and impact on the healthcare system. GSK invested £80 million on the SLS studies alone.

The SLS demonstrated clinical effectiveness of Relvar Ellipta both in COPD and asthma. In COPD, patients achieved a superior reduction in exacerbations compared with usual care. In asthma, patients initiated with the medicine had twice the odds of achieving an improvement in asthma control, compared with patients continuing usual care. 

Moreover, the inhaler device of Relvar Ellipta, known as the Ellipta inhaler, took 10 years of research to develop and over 200 scientists and engineers were involved in research, design and manufacturing. GSK has a variety of medicines for COPD and asthma that can be delivered through this one device. The benefits of this include the fact that patients are not required to learn how to use a different inhaler if, in the case of COPD, their disease progresses and they require a step-up in therapy. Equally, healthcare professionals will spend less time explaining how to use the device. Furthermore, this innovation in inhaler design has resulted in a device with lower critical errors made by patients, compared with commonly-used alternatives, as is shown by the Ellipta critical errors study.[5] 

The need for Supplementary Patent Certificate (SPC) to make investment sustainable

The estimated period of exclusivity that may be available for this product was factored into the decisions at all stages of this project, allowing us to make this investment to continue researching in an area with persistent unmet medical need. The active ingredients, FF and VI, are protected by separate patents, which expire in 2021 and 2022 respectively – for a medicine that has been approved in 2013. Hence, SPCs have been obtained in Europe and the effective loss of exclusivity for Relvar Ellipta is 2027, a period of 14 years from approval. Without the SPC, the period of exclusivity would be only 9 years. It should be noted that the 10-year term of regulatory data exclusivity for Relvar Ellipta will expire in 2023 – although this runs in parallel and therefore does not provide any effective additional protection.

It is highly unlikely that the extensive research to identify and develop this new medicine would have been viable without the potential to secure a reasonable period of exclusivity provided by the patent and the SPC. It is even more doubtful – had the period of exclusivity been shorter – that the additional research conducted with the Salford Lung Studies that allowed us to determine the advantages of the medicine under a real-life setting, and thereby allows for precious guidance for physicians and patients, would have been invested in.

The Relvar Ellipta story demonstrates that the SPC regulation operates to compensate innovators proportionately for patent term lost due to the regulatory timelines. It also shows that although other incentives or periods of exclusivity may apply, they generally run in parallel and do not therefore increase the overall duration of true exclusivity. It furthermore goes to show that existing incentives provide the right impetus for research in complex areas, thereby continuously improving patient outcomes.

Finally, all the above-mentioned innovation has been priced at a lower price than the same category older generation medicine Seretide, a demonstration that innovation does not necessarily come with higher prices. In that context, Sir Andrew Witty, former GSK CEO, has publicly stated that “all of the products we have launched most recently, we have launched at or below the prices of the older technologies that we are looking to replace.”

1 Wang,Haidong et al, The Lancet, Volume 388, Issue 10053, 1459 – 1544

2 GOLD Guidelines 2017

3 Van Boven, Job F.M. et al, Clinical and economic impact of non-adherence in COPD: A systematic review, in: Respiratory Medicine (2014), 108, 103- 113

4 Mika J.Mäkelä , et al, Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD, in: Respiratory Medicine (2013), Vol 107, Issue 10, pages

5 van der Palen J, et al. An open label crossover study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA® with other inhaler devices. Primary Care Respiratory Medicine 26, Article number: 16079 (2016)