Esbriet’s Promise and Potential as a PF Therapy

Esbriet (pirfenidone, Genentech) is an anti-fibrotic drug developed as a therapy for pulmonary fibrosis (PF), and was one of the first two drugs to receive approval for PF treatment in the United States. New data on Esbriet was recently presented by Dr. Steven Nathan, Medical Director, Advanced Lung Disease and Transplant Program at Inova Fairfax Hospital, at the American College of Chest Physicians Annual Meeting (CHEST 2015), held Oct. 24–28 in Montreal, Canada.

Pulmonary Fibrosis News, part of the Bionews Services group, had the opportunity to interview Dr. Nathan and Dr. Ben Kramer, vice president of Medical Affairs at Genentech, on the findings reported at CHEST 2015 and future plans for Esbriet therapy. Here is our interview:

PF News: Pirfenidone has been shown to slow disease progression, namely through a reduction in lung function decline. Now, you report that pirfenidone can reduce the risk of all-cause mortality in IPF patients, as well as IPF-related mortality in comparison to a placebo. These results are especially important since it is estimated that around two-thirds of the IPF patients die within five years after being diagnosed. Do you think that pirfenidone can make a significant difference on these estimates?

Dr. Nathan: Yes. I believe that it will, but this remains to be seen over time.

PF News: In the trials assessing pirfenidone, some of the patients discontinued the treatment. Was this decision based on adverse events? If so, could you comment on those?

Dr. Nathan: The discontinuations were mostly predicated on side effects. However, the majority of patients tolerated the pirfenidone very well. Obviously, the key to success is to keep patients on drug, and every attempt should be made to mitigate side effects with dose reduction or medications to control side effects such as nausea. It is also important that the patient take their medication with good solid meals, which will enable gastrointestinal tolerability. Also, strict instruction needs to be provided to avoid photosensitivity rashes.

PF News: The patient cohorts were followed in some cases up to 120 weeks after initiating treatment. Are there plans to follow these patients further? If so, do you expect to see a sustained effect for pirfenidone, or do you think there is the risk that pirfenidone might have its efficacy compromised in the long term, either due to the drug itself or due to the increasing debilitating health condition of the patient?

Dr. Nathan: We did follow these patients as long as possible. In fact, the data that I presented both at the European Respiratory Society (ERS) as well as the American College of Chest Physicians (CHEST) followed these patients as long as possible out as long as 120 weeks. But this is as far as we can carry it, since at that point patients were not continued in the study and many of these patients were then switched over to open label drug. I do not think that the efficacy will be compromised in the long term; however, obviously there will still be patients on drug who will succumb due to the disease.

PF News: Is Genentech considering the possibility of combining pirfenidone with other therapeutic drugs for IPF treatment?

Dr. Kramer: Yes. We remain committed to building on the success of Esbriet in addressing the significant unmet need in IPF, including exploring potential new therapies. Our investigational medicine lebrikizumab, which targets the protein interleukin 13 (IL-13), is in a Phase 2 trial to evaluate it as monotherapy and as add-on therapy to Esbriet for the treatment of IPF, and the FDA granted lebrikizumab orphan drug designation in IPF. Additionally, we plan to continue exploring the potential of Erivedge (our approved therapy for the treatment of advanced basal cell carcinoma) for people with IPF.

PF News: Given the fact that pirfenidone can slow IPF disease progression but unfortunately there is no evidence that it can stop it, do you think that IPF can, at this point, be considered a treatable disease or is it premature to assume it?

Dr. Nathan: Based on the approval of two medications for IPF, it is now a treatable condition, although not a curable disease. There is still more work to be done and need for additional medications to address this fatal condition.

Dr. Kramer: IPF is a treatable disease. Before October 2014, there were no approved medicines for the treatment of IPF. IPF care followed a supportive, palliative care paradigm. Now, medications like Esbriet have been proven to preserve lung function and slow IPF disease progression, bringing hope to people with IPF and their families.