Fibrotic remodelling occurs in many diseases. Thinking about idiopathic pulmonary fibrosis (IPF) as a ‘purely’ fibrotic condition, with currently unknown aetiology, may offer strategic insights into IPF drug development that are similarly applicable to other indications. In this blog we look at the adoption and cost-effectiveness of two approved IPF therapies, nintedanib and pirfenidone, and how these data impact wider drug development strategies.
Cottin and coworkers1 have recently shown that, untreated, IPF is associated with an all-cause mortality of 50% at 3 years. This is based on a French cohort defined by patients with a diagnosis of IPF and no differential diagnosis of other fibrotic lung disease. Patients treated with nintedanib or pirfenidone had 3-year all-cause mortality incidence rates of 31% and 26%, respectively, based on the same dataset. Also at 3 years, the incidence of IPF-related hospitalization was 42%. Somewhat, intriguingly, patients on therapy had cumulative incidence rates in the same range (44% and 48% for nintedanib and pirfenidone, respectively). One conclusion of this is that antifibrotic therapy indeed works and prolongs life in IPF patients, albeit modestly, but has no effect on other aspects of IPF, in this case exacerbations and hospitalizations – aspects which are important for patients’ quality of life.
Are IPF therapies cost-effective?
A second new datapoint is an investigation of the cost-effectiveness of nintedanib and pirfenidone in the US compared to symptom management. Results of this study indicate that drug therapy costs more than $110,000 per year (compared to $12,291 for symptom management). The average cost to achieve one additional quality-adjusted life-year for patients with IPF using nintedanib or pirfenidone was calculated as approximately USD 1.6 million. (Note that a ‘quality-adjusted life-year’ is a mathematical construct that, for example, could also be achieved by prolonging life for 1 year in 4 patients, which each patient rating the quality of life for that year with 20%.)
The future of drug therapy in IPF
What does this mean for future drugs intended to treat IPF? Maybe these articles challenge the view 2that the current standard of care works well enough and would ‘only’ need a better safety profile. Rather one conclusion is that any new drug must improve on the efficacy of the current standard of care (which at some point will become generic and will thus be cheap) in terms of slowing or halting FVC decline. However, an additional conclusion could be that to make a difference, a new drug must significantly improve the quality of life of patients against a progressive and fatal disease – with fewer exacerbations, less hospitalizations, and impact on patient-centric parameters like feeling short of breath or coughing.
Of course, ideally a new drug will improve on both these characteristics when given on top of the current standard of care – a setting which we consider required for larger clinical studies and as at least initial prescription setting3.
If you have a project targeting IPF and want to discuss how this thinking can be built into the development program, do get in touch to start the conversation.