Last updated Jan. 14, 2022, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD
Esbriet (pirfenidone) is an oral treatment for idiopathic pulmonary fibrosis (IPF) that was originally developed by Intermune, which later merged with Roche. Esbriet was first approved in the European Union in 2011 and in the U.S. in 2014. The therapy is currently being marketed by Genentech, a Roche company.
In the U.S., Esbriet is currently being reviewed as a potential treatment for unclassifiable interstitial lung disease (UILD).
How does Esbriet work?
Pulmonary fibrosis is characterized by lung inflammation and scarring. Esbriet is able to slow the progression of lung scarring. Although its exact mechanism of action is not fully understood, the therapy is thought to act at least partly by blocking the activity of a pro-inflammatory molecule called transforming growth factor-beta (TGF-beta), which is a known driver of lung scarring.
Esbriet in clinical trials
Genentech launched two Phase 3 clinical trials — CAPACITY-004 (NCT00287716) and CAPACITY-006 (NCT00287729) — to test Esbriet in adults with IPF. CAPACITY-004 enrolled 435 IPF patients, and CAPACITY-006 enrolled 344 patients. In both trials, participants were randomly assigned to receive placebo or Esbriet. Both trials tested a high dose of Esbriet (2,403 milligrams per day); CAPACITY-004 also tested a lower dose (1,197 mg a day).
Both CAPACITY trials evaluated the effect of treatment on forced vital capacity (FVC), a common lung function measure, after 72 weeks (just under 1.5 years). Esbriet significantly slowed FVC decline in patients participating in CAPACITY-004; however, in CAPACITY-006, the treatment’s effect on FVC was not statistically significant. In both trials collectively, there were fewer deaths among participants given the higher dose of Esbriet than those given a placebo (6% vs. 8%).
Given the ambiguous results from the CAPACITY studies, U.S. regulatory authorities asked for further research before they would consider approving Esbriet. Genentech then sponsored a third Phase 3 trial called ASCEND (NCT01366209) to confirm Esbriet’s safety and efficacy. The trial enrolled 555 participants, who were given Esbriet at a dose of 2,403 mg per day, or a placebo, for 52 weeks (about one year).
Results from ASCEND showed that significantly fewer patients given Esbriet experienced a FVC decline of 10% or more over the course of the trial or who died, compared with those given a placebo (16.5% vs. 31.8%). Additionally, significantly more participants given Esbriet had no FVC decline (22.7% vs. 9.7%).
Analyses of pooled data from ASCEND and the CAPACITY studies suggested that Esbriet reduced the overall risk of death at one year by 48%. The risk of death due to IPF, specifically, was reduced by 68% with Esbriet compared with placebo.
Esbriet also has been evaluated in IPF patients in two open-label clinical trials — PIPF-012 (NCT00080223) and RECAP (NCT00662038) — which helped to collect information on the medication’s safety profile, which was consistent with that seen in previous studies.
Esbriet also has been evaluated in a number of clinical trials for indications other than IPF, ranging from kidney disease to COVID-19. The medication’s efficacy in UILD was demonstrated in a 24-week Phase 2 trial (NCT03099187) that enrolled 253 patients. Results showed that treatment with Esbriet significantly slowed FVC decline relative to a placebo.
Esbriet is administered orally and is recommended to be taken with food (801 mg three times daily) to reduce nausea and dizziness. It is mostly metabolized in the liver and excreted in the urine within 24 hours.
The most common side effects associated with Esbriet include nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia (indigestion), dizziness, vomiting, loss of appetite, gastro-esophageal reflux disease, stuffy or runny nose, insomnia, weight loss, and joint pain.
Esbriet can cause rashes or photosensitivity — skin damage caused by exposure to bright lights, particularly sunlight. Thus, it is recommended that people on the medication avoid direct sun exposure and use sunscreen or other forms of protection. Esbriet can also cause the levels of certain liver enzymes (aspartate aminotransferase, alanine aminotransferase, and bilirubin) to rise, which should be monitored before and during treatment.
Exposure to Esbriet can be increased if a person is also taking medications that strongly inhibit the metabolic liver enzyme CYP1A2, such as the antibiotic ciprofloxacin or the antidepressant fluvoxamine. The dosage of Esbriet should be reduced if given along with ciprofloxacin; Esbriet is not recommended for use in combination with fluvoxamine.
Smoking may decrease exposure to Esbriet, which may limit the medicine’s effectiveness. Esbriet is not recommended for use in people with end-stage kidney disease on dialysis or those with severe liver impairment.
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