Esbriet Safe but Less Effective in Severe IPF Patients After 6 Months of Treatment, Small Study Says

Esbriet Safe but Less Effective in Severe IPF Patients After 6 Months of Treatment, Small Study Says

A retrospective real-world study found that the benefits of Esbriet (pirfenidone) in people with advanced idiopathic pulmonary fibrosis (IPF) appeared to diminish after six months of treatment, although side effects were similar to those reported in previous clinical trials.

These results were reported in “Safety and efficacy of pirfenidone in severe Idiopathic Pulmonary Fibrosis: A real-world observational study,” published in the journal Pulmonary Pharmacology and Therapeutics.

IPF is a progressive and debilitating disease of unknown cause that is characterized by thickening and scarring (fibrosis) of lung tissue, which makes breathing difficult and decreases the amount of oxygen the lungs can supply to the major organs.

Its treatment was largely limited to supportive care and lung transplants until Esbriet (pirfenidone; marketed by Genentech) along with Ofev (nintedanib; by Boehringer Ingelheim) were approved in 2014.

Esbriet has been shown to slow disease progression in IPF as measured by a decline in forced vital capacity (FVC), or the amount of air a person can forcibly exhale after taking the deepest breath possible.

IPF patients with severe lung function impairment can represent a significant portion of people in a real-life clinical setting, although they are usually not included in Phase 3 trials, the study noted. Researchers for this reason wanted to assess Esbriet’s safety and efficiency in advanced IPF patients to help clinicians in treatment decisions.

The team reviewed medical records of 43 patients with severe IPF who received 2,403 mg of Esbriet a day for one year.


Esbriet use in these patients was found to be associated with a trend toward functional improvement at six months post-treatment initiation, but the therapeutic benefits appeared to diminish six to 12 months after treatment start.

The team noted that the rapid functional deterioration observed during that period was consistent with a large proportion of rapidly progressing patients. These patients, identified based on a 5% decline in FVC after three months of treatment, are known to respond poorly to Esbriet.

The most common adverse events were gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%), and they were mild to moderate in severity. These events were consistent with the drug’s safety profile previously reported in three large randomized controlled clinical trials: Phase 3 ASCEND trial (NCT01366209, 52 weeks) and the CAPACITY trials (NCT00287716 and NCT00287729, 72 weeks).

Adverse events experienced by those with severe IPF led to treatment discontinuation in 20.9% of the cases, which was slightly higher than those reported in the ASCEND (14.4%) and CAPACITY (15%) trials. Those studies included patients with mild-to-moderate disease severity.

According to the researchers, the study “adds meaningful knowledge on the safety profile and therapeutic effects of pirfenidone on an underestimated majority of IPF patients.”

“Our preliminary findings indicate a time-limited therapeutic profile of pirfenidone in IPF patients with rapid disease progression. Further prospective studies will help us identify subgroups of patients with different responses to pirfenidone and thus apply precision medicine therapeutic approaches,” the team concluded.


  1. ric ellens says:

    LAVAL, QC, Sept. 25, 2017

    Prometic moving immediately to formalize enrollment of specialist clinical sites across the United States
    U.S. IND to be followed by clinical trial applications in Canada, Europe, Australia and Japan throughout Q4 2017
    Prometic plans to supplement the IND with a protocol for a study of PBI-4050 monotherapy in IPF patients in October 2017

    LAVAL, QC, Sept. 25, 2017 /CNW Telbec/ – Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) today announced that its oral anti-fibrotic lead drug candidate, PBI-4050, has received U.S. Food and Drug Administration Investigational New Drug (IND) approval to commence its pivotal Phase 2/3 clinical trial in patients suffering from idiopathic pulmonary fibrosis (IPF).

    The pivotal Phase 2/3 clinical trial is a two-stage adaptive, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of PBI-4050 when combined with nintedanib (OFEV™, Boehringer Ingelheim) in subjects with IPF. The number of subjects required to be enrolled has been based on the results seen in the recently-completed open label study of PBI-4050 in IPF. The Phase 2 stage will enroll 375 subjects with IPF, who will be randomly assigned to one of three groups: 1) 125 subjects who will receive placebo + nintedanib, 2) 125 subjects who will receive PBI-4050 800 mg + nintedanib or 3) 125 subjects with PBI-4050 1200 mg + nintedanib. An independent Data and Safety Monitoring Board (DSMB) will conduct an interim 26-week analysis, and based on the safety and efficacy results, will recommend whether the study should continue into Phase 3 stage and which dose of PBI-4050 should be continued. This Phase 3 stage would randomize an additional up to 450 subjects to receive nintedanib plus either placebo or the chosen PBI-4050 dose.

    Prometic has already completed an open label Phase 2 study in patients who received PBI-4050 for 12 weeks in addition to either pirfenidone, nintedanib, or placebo. The study showed the Forced Vital Capacity (FVC) remained stable in patients on PBI-4050 alone (n=9, FVC -12 ml) and in patients on PBI-4050 in combination with nintedanib (n=15, FVC +2 ml). In contrast, the FVC declined significantly in patients receiving PBI-4050 in combination with pirfenidone (n=16, FVC -105 ml). PBI-4050’s plasma concentration was sub-therapeutic at 50% of the expected level in patients receiving PBI-4050 in combination with pirfenidone, suggesting a drug-drug interaction.

    “We are very encouraged by the results of our open-label trial of PBI-4050 in combination with nintedanib, and are pleased to advance the clinical development plan with this pivotal study”, said Dr. John Moran, Prometic’s Chief Medical Officer. “IPF is a very serious condition and we believe that patients may benefit from this novel therapeutic approach. We have multiple key opinion leaders who have expressed a wish to participate in the study, and now that the IND has been cleared we can begin a formal study startup”.

    Pierre Laurin, Prometic’s President and Chief Executive Officer, stated, “We are very excited to be entering the pivotal stages of our IPF clinical program, which is another important milestone towards bringing this therapy to patients who suffer from IPF. We believe that PBI-4050 is an important advancement in this indication and represents a potential significant step forward for helping patients ,.,.,.,.

  2. I am confused about something in this article. Are the subjects starting Esbriet when they are in the severe category or are they talking about patients who have declined yo the severe category. My fvc is 50% but changes. It goes up and down. One of my tests went down to 44% we think due to fires. Now that I’m on medicare, it looks like my part d is fitting off at 50%. I am 57 still active and this question is very important as I may be fighting to keep this med. thank you. Christine

Leave a Comment