General Information

Esbriet (pirfenidone) is an oral antifibrotic p38 MAP kinase inhibitor that reduces growth factor signaling.

Esbriet is specifically indicated for the treatment of idiopathic pulmonary fibrosis.

Esbriet is supplied as a capsule for oral administration.

The recommended daily maintenance dosage of Esbriet is 801 mg (three 267 mg capsules) three times a day with food for a total of 2403 mg/day.

Doses should be taken at the same time each day. Upon initiation of treatment, titrate to the full dosage of nine capsules per day over a 14-day period as follows:

Days 1 through 7: 1 capsule three times a day with food
Days 8 through 14: 2 capsules three times a day with food
Days 15 onward: 3 capsules three times a day with food

Side Effects

Adverse effects associated with the use of Esbriet may include, but are not limited to, the following:

nausea

rash

abdominal pain

upper respiratory tract infection

diarrhea

fatigue

headache

dyspepsia

dizziness

vomiting

anorexia

gastro-esophageal reflux disease

sinusitis

insomnia

weight decreased

arthralgia

Clinical Trial Results

The FDA approval of Esbriet was based on three phase 3, randomized, double-blind, placebo-controlled, multicenter trials (Studies 1, 2, and 3).

Study 1 was a 52-week trial comparing Esbriet 2403 mg/day (n=278) versus placebo (n=277) in patients with IPF. Study 2 and Study 3 were nearly identical to each other in design, with few exceptions, including an intermediate dose treatment arm in Study 2. Study 2 compared treatment with either Esbriet 2403 mg/day (n=174) or Esbriet 1197 mg/day (n=87) to placebo (n=174), while Study 3 compared Esbriet 2403 mg/day (n=171) to placebo (n=173). Study drug was administered three times daily with food for a minimum of 72 weeks. Patients continued on treatment until the last patient completed 72 weeks of treatment, which included observations to approximately 120 weeks of study treatment. The primary endpoint was the change in percent predicted forced vital capacity (%FVC) from baseline to study end, measured at 52 weeks in Study 1, and at 72 weeks in Studies 2 and 3.

In Study 1, the primary efficacy analysis for the change in %FVC from baseline to Week 52 demonstrated a statistically significant treatment effect of Esbriet 2403 mg/day (n=278) compared with placebo (n=277) using a rank ANCOVA with the lowest rank imputation for missing data due to death. In Study 2, there was a statistically significant difference at Week 72 for the change in %FVC from baseline. In Study 3, there was no statistically significant difference at Week 72 for the change in %FVC from baseline. In Study 1, a reduction in the mean decline in FVC (in mL) was observed in patients receiving Esbriet 2403 mg/day (-235 mL) compared to placebo (-428 mL) (mean treatment difference 193 mL) at Week 52. In Study 2, a reduction in the decline in FVC volume was also observed in patients receiving Esbriet 2403 mg/day compared with placebo (mean treatment difference 157 mL) at Week 72. There was no statistically significant difference in decline in FVC volume seen in Study 3.