Esbriet for IPF: Reconsidering Its Role

A retrospective look at pirfenidone (Esbriet) for idiopathic pulmonary fibrosis (IPF) — since it was approved by the US Food and Drug Administration (FDA) in October 2014 — has at least one physician calling for changed patient perspective of the treatment.

In a lecture focused on advancing IPF treatment at the 2017 Annual CHEST Meeting in Toronto, ON, CA, Gordon L. Yung, MD, FCCP, explained the true goal set by Esbriet treatment.

Yung, a Professor of Medicine at the UC San Diego School of Medicine, said the antifibrotic’s success is only in delaying disease progression.

“Because the medication does not reverse fibrosis, when you give the patient the medication, you’ve got to set the right expectations,” Yung said. “They have to know why you’re giving it, because I can guarantee you the next time, they’re going to say ‘Hey, I do not feel better’.”

In fact, more than any other drugs, Yung said Esbriet is the most to set a “stage” for in patients’ minds.

There’s various elements that could influence misperception of the drug’s efficacy and tolerability in patients. Yung said the “worst thing” a physician could do after prescribing an antifibrotic is advising the patient to come in for a check-up shortly after beginning the therapy.

“They’re not going to feel better and if there’s side effects, they’re going to quit,” Yung said.

Esbriet, which was previously rejected for IPF therapy by the FDA in 2010 in response to its clinical data, was backed by 3 clinical trials at the time of its approval 3 years ago.

The predominately plasma-bound oral inhibitor was evaluated in more than 1,200 IPF patients with varying ranges of clinical characteristics and select comorbidities, Yung said. Though the initial ASCEND trial only ran for 52 weeks and the 2 proceeding trials ran for 72 weeks each, the 3 studies shared a consistent element.

“The history is complicated, and it makes the data analysis a little more difficult,” Yung said. “In 3 trials, the main thing is patients were actually enrolled in a relatively early part of the disease.”

The Forced Vital Capacity (FVC), a common metric for lung diseases such as IPF, was reported at an approximate mean of 70% at the time of baseline in the clinical trials, Yung said. At that rate, IPF is considerably mild — with average FVC ranging at 80% or more.

Given the disease’s early progression, patients showed declines in FVC and lung function in the year-plus analyses. Yung argued that, while 9 of ever 10 patients would decline in lung function in that span, Esbriet would double their chances of stabilizing, and that ASCEND patients taking therapy maintained a mean 193mL of more lung function at week 52.

In FVC, one-third of patients would have a significant decline in rate (10%) over that year. Yung said the treatment was capable of cutting that decline in half.

While those benefits of stabilizing a still-progressing disease are not as evident to a patient, adverse events are. Yung noted that only 3 side effects were prevalent in Esbriet patients: liver enzymes, skin rashes, and gastrointestinal conditions (the most common).

Enzymes did not cause serious harm to any patients at the tested dosage rates, Yung said. He advised patients stay conscientious of sun exposure’s effect for those on antifibrotic therapy, and said a slowed dosing increase and ingesting therapy with a meal could address any possible gastrointestinal issues.

What’s more, Yung said these are the final limits of concern. Esbriet was previously approved for marketing by the European Commission in 2010, and was granted China FDA approval in 2011.

Even before then, it was undergoing clinical research.

“If you count the original studies in Japan, it’s been more than 10 years now,” Yung said.

The presentation, "Advancing the Treatment of IPF: A Patient Journey," was sponsred by Roche Group's Genentech, a developer of Esbriet.