Esbriet (pirfenidone) is as safe a treatment for idiopathic pulmonary fibrosis (IPF) in the long-term as it is already known to be from shorter term studies, data presented at the recent European Respiratory Society (ERS) International Congress 2016 showed.
In addition, two other studies presented research highlights of the drug’s importance to the IPF community. One study demonstrated that dose adjustment is an appropriate way of managing the side effects of Esbriet treatment, allowing patients to continue their treatment with a high-dose intensity.
Strong support for the effectivity of Esbriet also came from a study finding that, compared to best supportive care, the drug can prolong life expectancy in IPF patients by nearly three years.
All the studies used data from randomized Phase 3 clinical trials — two studies named CAPACITY, and the ASCEND study — and the open-label extension study RECAP. The data on Esbriet, made by Genentech, was presented at ERS 2016, held in London on Sept. 3–7.
Long-term data show no new safety issues
Two presentations dealt with the long-term safety of Esbriet treatment. One looked at the study, “Long-term safety of pirfenidone (PFD) in people with idiopathic pulmonary fibrosis (IPF): pooled analysis of 4 clinical trials,” and was given by Dr. Paul Noble from Los Angeles.
Together, these studies included 1,216 patients with a median treatment time of 25.9 months. The vast majority of patients, 99%, reported one or more treatment-emergent adverse events during the study, and 57% reported a severe adverse event.
In clinical trials, researchers usually speak of ‘treatment-emergent adverse events’ rather than side effects. Such events include effects that are both caused by the treatment, and those that are caused by other factors, such as the disease itself. Treatment emergent refers to the fact that the effects appeared after the treatment started.
This study revealed that the most common severe adverse event was IPF, affecting 21.5%, and pneumonia, appearing in 9.3% of the patients.
The second presentation focused on safety issues found in the study, “Final analysis of RECAP, an open-label extension study of pirfenidone in people with idiopathic pulmonary fibrosis (IPF).” This study was an open label extension for patients who completed one of the CAPACITY or ASCEND Phase 3 trials.
This study recruited 1,058 participants who took Esbriet for an average of 122 weeks. Safety data was similar as in the study analyzing all trials, with 98% reporting at least one adverse event and 54% reporting a serious adverse event. Again, the most common event was IPF.
During the study, 231 patients (22%) died, and the most common cause of death was IPF. Adverse events led to 42% of the participants stopping the treatment. Again, IPF was the major cause cited in 17% of the participants who quit, while other causes were pneumonia (1.2%), respiratory failure (1.2%), acute respiratory failure (1.1%), rash (1.1%), and nausea (1.0%).
Both studies showed that long-term Esbriet treatment is linked to the same safety issues as short-term treatment.
Dose modifications to manage side effects
A study, titled “Dose modifications and dose intensity during treatment with pirfenidone,” presented by Dr. Steven Nathan from Falls Church, Virginia, also evaluated data from the ASCEND and CAPACITY trials. The study explored if dose reductions and interruptions could help patients manage gastrointestinal and skin-related adverse drug reactions, which about 30% of patients experience.
The study followed 623 patients receiving Esbriet, and 624 placebo-treated participants. The mean daily Esbriet dose was 2,105 mg. During the study, 32.7% of Esbriet-treated and 11.4% of placebo-treated participants reduced their doses. Also, 34.3% and 18.6%, respectively, interrupted the treatment in the two groups.
Patients receiving Esbriet reduced the dose for an average of 28 days, and those who interrupted the treatment did so for about 14 days. Doses were adjusted after a median of about 95 days from treatment start, except for those who vomited, who adjusted doses after about 28 days.
A dose of 90% or more of the maximum daily dose (2,403 mg/day) was achieved by 424 of 623 patients. Those who managed to stay on a high-dose intensity treatment had a lower decline in lung function than both placebo-treated patients and those whose dose levels were less than 90 percent.
Finally, the study, “Predicting life expectancy for pirfenidone and best supportive care (BSC) in idiopathic pulmonary fibrosis (IPF),” was presented by Dr. Mark Fisher from St. Albans in the U.K. The study compared survival data for patients treated with Esbriet in the four clinical trials with data from 1,136 patients receiving only best supportive care. The best supportive care data was accessed through two independent large IPF registries — the Inova Fairfax Hospital database and the National Jewish Health Interstitial Lung Disease (NJH-ILD) database.
The mean life expectancy in patients receiving Esbriet was 8.7 years, between 2.6 and 2.8 years longer than that calculated for patients in the two registries used (5.9 years Inova, and 6.1 years NJH-ILD).