Esbriet Dose Reductions Don’t Affect Its Potential to Manage IPF, Study Shows

Esbriet Dose Reductions Don’t Affect Its Potential to Manage IPF, Study Shows

Modifying the dose of Esbriet (pirfenidone) can effectively reduce the number of treatment-related adverse events without affecting the drug’s potential to manage idiopathic pulmonary fibrosis (IPF), a new retrospective analysis of data from Phase 3 clinical trials shows.

The findings of this recent post-hoc analysis were published in the journal BMJ Open Respiratory Research in a study titled, “Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials.

Marketed by Genentech, Esbriet is an approved therapy used to manage the symptoms of IPF and prevent its worsening. It is a dual acting agent that modulates the response of fibroblasts — the most common type of connective tissue cell — while reducing inflammation and tissue scarring.

The safety and effectiveness of Esbriet was demonstrated in three independent pivotal Phase 3 trials: CAPACITY-2 (NCT00287716), CAPACITY-1 (NCT00287729), and ASCEND (NCT01366209).

These studies demonstrated that Esbriet could effectively ease IPF patients’ lung function, as well as reduce the risk of disease progression and mortality.

Despite its therapeutic potential, during the trials almost all Esbriet-treated patients experienced at least one treatment-related adverse event. Also, more treated patients discontinued the therapy prematurely due to symptoms of toxicity, such as gastrointestinal and skin-related events.

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As Esbriet’s effects have been reported to be dependent on the dose used, it has been suggested that dose modifications could help manage the number of adverse reactions. Until now, though, it remained unclear if this alternative approach could change the effectiveness of the treatment to manage IPF.

Researchers re-analyzed pooled data of the three pivotal trials, comprising 1,247 IPF patients who were randomized to receive oral Esbriet (2,403 mg per day) or a placebo for up to 72 weeks.

Results showed that about the same proportion of patients in the Esbriet and placebo groups had temporary dose reductions during the trials — 59.7% vs. 60.1%, respectively. But more patients treated with Esbriet had to permanently reduce the dose — 31.5% vs. 20.8% in the placebo group.

Most of the interruptions happened during the first six months of treatment, whereas dose modifications were reported throughout the duration of the trials.

When researchers reviewed the therapy’s efficacy data, they found that regardless of the administrated dose, Esbriet showed a clear benefit in preventing decline of forced vital capacity (FVC, a measure of lung function), exercise capacity, or death at one year compared to placebo.

“Despite dose reductions and interruptions, most patients with IPF maintained relatively high dose intensity on [Esbriet] without compromising its treatment effect compared with placebo,” the researchers wrote.

A safety comparison between groups revealed that those taking a lower dose of the treatment had fewer adverse events, such as nausea, compare to those taking higher doses of Esbriet.

While dose reductions were seen to be a “useful management tool to reduce the risk of treatment discontinuation,” the researchers highlight that the study results still do not set a minimum effective dose of Esbriet that could be used during a treatment adjustment period.

Also, the analysis failed to find any evidence of a relationship between body weight and the effectiveness and safety of Esbriet that could support a weight-based dosing.

Still, the team concluded that “dose modifications are an appropriate strategy to manage adverse events and to help ensure long-term persistence with [Esbriet] treatment.”

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  1. Donald Otis says:

    Well, ok, but one truth is the nausea thing – the original format for pirfenidone was, for me, the 267 capsules. Capsules fall apart in the stomach, almost immediately, and caused me great discomfort. I lost a lot of weight, largely because I couldn’t eat. Actually, it was horrible, but I liked the science behind the drug, and I stuck it out.

    This last January, with no apparent order, I began receiving the 801 pills. These don’t digest until well past the stomach, and the nausea has been turned way down. So far down that I unretired (you can pay Social Security back during that first year, and it is like you never retired), and am working, feeling as good as I have since I got IPF in 2015.

    If you are on the capsules, please tell your doctor to figure out how to go to the pill format. It is the same outrageous cost, it is the same 2404/day, but it is so much better!

  2. Cindy Dennard says:

    My husband has been on Esbret for about 6 mons. He built up to 9 pills a day but had to cut back to 6 a day due to indigestion. He is now build back up to 9. Thank goodness he has had no serious side effects. He is also on Esbret and his breathing is much improved. He only uses his oxygen when he has to walk a lot. He also does plumunary rehab three times a week. Thank goodness he was able to dance with his granddaughter at her wedding.

  3. Geo Warbeck says:

    I’m a year or so along with Esbriet (pirfinedone), side effects seem to have abated over that time, tolerance mostly, I think. Take it with some food.

    Half Life of Esbriet in your system is 5 hours, and even though they said not to fool with the dosage, I think that this study indicates that you could drop to two pills (@ 267 mgs ea) and take them a little more frequently and still maintain (or maybe even improve) your system’s saturation consistency.

    But what do I know?

    What I’d like them to find is a biomarker to indicate the drug(s) are working (or not). In the meantime I’ll assume (gratefully) that it is; disease progress for me (now) is slow.

  4. R. Stevens says:

    Interesting comments. It would useful to know how many liters of oxygen these people require at rest. Not a lot of data regarding that. Does it work as well for high oxygen requirements as for low.

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