The Prix Galien Canada 2014 – Innovative Drug Product has been awarded to InterMune Canada (Roche) for pirfenidone (Esbriet).
Until now, the only treatment available to patients with idiopathic pulmonary fibrosis (IPF) has been lung transplantation or palliative care. Idiopathic pulmonary fibrosis is a chronic, progressive disorder of lung scarring that affects mainly older patients and has a death rate worse than most cancers. No drug has been shown to alter the course of this disease.
Pirfenidone is a heterocyclic pyridone with a somewhat unclear mechanism of action although it is thought to be mediated, at least in part, through the inhibition of the expression of transforming growth factors beta 1.
Originally developed in the 1970’s as an anti-inflammatory agent, the drug was rediscovered in the 1990’s as an antifibrotic agent and in 2002 was licensed by InterMune in North America, Europe and Australia and by Shionogi and Co. Ltd. for Japan. In 2014, Roche acquired InterMune, the company that has sponsored the majority of the clinical trials. Health Canada approved the drug in 2013 for the treatment of mild to moderate idiopathic pulmonary fibrosis. Three large phase 3 placebo-controlled clinical trials involved 9 Canadian centres. Primary outcome was the change in the percentage of predicted forced vital capacity (FVC) from baseline to week 72. There was no statistically significant decrease in all-cause mortality in the first two trials but there was a statistically significant increase in progression-free survival (PFS) in one of the two initial trials. Similarly, there was a statistically significant improvement in the rate of decline in the per cent predicted FVC in one but not in both of these trials. Pooled analysis of data from these two trials did favour pirfenidone for all of the above criteria. At the request of the FDA, a third phase 3 clinical trial was performed and recently published. In this trial, all the primary end points were achieved, including a significant reduction in the one-year rate of decline of FVC. There was also a reduction in the decline in the 6-minute walking distance in the treated patients compared with those who received placebo. A prespecified analysis combining the results of all three randomized placebo-controlled clinical trials was significant for all cause death and death due to idiopathic pulmonary fibrosis. A long-term open-label trial is ongoing for all patients who completed any of the three initial studies. The most frequent adverse drug reactions (ADRs) included gastrointestinal upset, rash, and photosensitivity and ADRs resulted in treatment discontinuations in 9% of the pirfenidone-treated group vs 3% of the placebo-treated group. Because the drug is metabolized by the CYP450 system, drug interactions will require careful monitoring.
Dr. Jean Gray, President of the Jury of Prix Galien Canada and Dr. Nozhat
Choudry, Director, Medical Affairs of InterMune Canada (Roche).
Pirfenidone is the first drug available to patients with idiopathic pulmonary fibrosis that appears to alter the course of the disease. Although the compound has been around for almost three decades, the recognition of its potential therapeutic benefits and the carefully conducted and large-scale clinical trials in a relatively rare disorder now offers hope to patients with idiopathic pulmonary fibrosis.
So for rediscovering and developing the compound for a previously untreatable disease, the Prix Galien for Innovative Produce is awarded this year to InterMune Canada (Roche) for pirfenidone (Esbriet).