Esbriet Can Prolong Pulmonary Fibrosis Patients’ Lives, Review of Several Studies Reports

Esbriet Can Prolong Pulmonary Fibrosis Patients’ Lives, Review of Several Studies Reports

Esbriet (pirfenidone) can prolong idiopathic pulmonary fibrosis (IPF) patients’ survival, according to a review of clinical trials covering the anti-inflammatory and anti-fibrotic agent.

Researchers also said that Esbriet is safe, but does not help every IPF patient.

The study, “Role of pirfenidone in the management of pulmonary fibrosis,” appeared in the journal Therapeutics and Clinical Risk Management. It was conducted by Keith C. Meyer of the University of Wisconsin Lung Transplant and Advanced Lung Disease Program and Catherine A. Decker of the University of Wisconsin School of Medicine and Public Health.

Pulmonary fibrosis is the most common interstitial lung disease, or ILD, a group of disorders that involve scarring of lung tissue. It can lead to progressive decline in lung function, poor quality of life, and early death.

IPF affects up to one in 200 older people. Patients’ median survival rate is only three to five years after diagnosis.

The disease’s progression can be worsened by comorbidities, or other disorders, including pulmonary hypertension and sleep-disordered breathing. Scientists believe it is triggered by damage to protective epithelial cells in the alveoli, the tiny air sacs at the end of the lungs’ respiratory tree, and the release of cytokines that trigger inflammation. Cytokines are molecules that promote cell to cell communication in immune responses and stimulate the movement of cells toward sites of inflammation, infection and injury.

Previous studies have indicated that IPF fails to respond to immunotherapy. Recent clinical trials have demonstrated that novel anti-fibrotic agents have improved lung function over time, however. Anti-fibrotics ameliorate lung-tissue thickening and scarring.

Esbriet slows IPF patients’ decline in respiratory function and increases their progression-free survival, according to the review. It also reduces mortality, which other anti-fibrotic therapies such as Ofev (nintedanib) are unable to do, researchers said.

Based on these findings, the United States Food and Drug Administration (FDA) approved Esbriet for treating IPF in 2014.

More recently, the ASCEND phase 3 clinical trial (NCT01366209) supported Esbriet’s effectiveness. The study involving 555 patients showed that Esbriet improved respiratory function, progression-free survival, and ability to exercise.

Importantly, a combined analysis of two clinical trials — ASCEND (NCT00287716) and CAPACITY (NCT00287729) — indicated that factors such as patient age, race, smoking status and geographic origin had no impact on Esbriet’s effectiveness.

The clinical trials have also shown that prolonged treatment — that is, beyond six months — continued to reduce the risk of IPF patients’ respiratory decline and death. In addition, pooled data from five clinical studies covering 1,299 patients supported a previous finding that Esbriet is well-tolerated.

Another significant finding was that a combination of Esbriet and the amino acid N-acetylcysteine worsened IPF patients’ respiratory function, compared with Esbriet alone. The discovery came out of the recent PANORAMA phase 2 trial (2012-000564-14).

Although the results on Esbriet are encouraging, the researchers who did the review said doctors should approach its use with caution. That’s because not all IPF patients have better respiratory function and live longer after taking it.

But “individuals with more rapidly declining lung function prior to beginning pirfenidone treat­ment are more likely to experience benefit,” the researchers wrote.

Side effects of Esbriet include gastrointestinal problems, skin reactions, weight loss, anorexia and fatigue, according to the review. Patients taking it should avoid smoking and drugs that inhibit Esbriet’s metabolism in the liver, the researchers said.

Those taking Esbriet should be carefully monitored, particularly those with severe liver or kidney dysfunction, they said.

The benefits of early treatment with Esbriet, compared with the risks, have yet to be investigated, the researchers said. They also called for studies on the potential benefits of using a combination of Esbriet and Ofev, and on whether Esbriet can help patients with advanced cases of IPF.

“Prior to initiating treatment with pirfenidone, a thor­ough dialogue with the patient, which includes an educational overview of the benefits, risks, and limitations of therapy, is recommended,” the researchers concluded.

 

 

15 comments

  1. Ric ellens says:

    Story image for pirfenidone pbi-4050 from Lung Disease News
    FDA Agrees with ProMetic’s Protocol for PBI-4050 in IPF Clinical Trials
    Lung Disease News-2 hours ago
    We are very pleased that the FDA concurs with our decision to exclude a combined pirfenidone [Esbriet] and PBI-4050 treatment arm in the …

    • Ric Ellens says:

      Canada NewsWire

      LAVAL, QC, Feb. 22, 2017

      Early evidence of efficacy of PBI-4050 as a monotherapy and in combination with one of the commercially available drugs confirmed
      PBI-4050 continues to be very well tolerated, whether used alone or in combination with nintedanib or pirfenidone
      LAVAL, QC, Feb. 22, 2017 /CNW Telbec/ – ProMetic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (“ProMetic” or the “Corporation”) announced today positive results from its completed open label Phase 2 clinical trial in subjects suffering from idiopathic pulmonary fibrosis (“IPF”). In addition to demonstrating that PBI-4050 is safe and very well tolerated, an objective of this study was to seek early evidence of a clinical benefit with PBI-4050 treatment, whether administered alone or in addition to either of the drugs approved for the treatment of IPF, nintedanib or pirfenidone. These results confirm the preliminary results previously announced by Prometic on November 17, 2016, following the first 30 subjects’ completion of 12 weeks of treatment.

      image: https://mma.prnewswire.com/media/470739/ProMetic_Life_Sciences_Inc__ProMetic_s_PBI_4050_continues_to_dem.jpg

      The comparisons shown herein between the results in this study and other larger phase 3 clinical studies are only made to provide some provisional guidance in terms of the potential clinical benefits of PBI-4050 for IPF patients. (CNW Group/ProMetic Life Sciences Inc.)

      A total of 40 subjects were enrolled in the study conducted in 6 sites across Canada and all have completed the 12 weeks of treatment; 9 subjects received PBI-4050 alone, 16 received PBI-4050 & nintedanib and 15 received PBI-4050 & pirfenidone. The baseline characteristics of the subjects enrolled in this study were similar to those enrolled in prior IPF randomized controlled studies conducted by other pharmaceutical companies, namely ASCEND and INPULSIS.

      As was demonstrated in these previously mentioned large clinical trials, IPF subjects typically experience a progressive decline in respiratory function. In contrast, in the ProMetic clinical study, the respiratory function of the subjects, measured as the forced vital capacity (FVC (ml)), remained stable after 12 weeks of treatment, in subjects treated with PBI-4050 alone and in those receiving PBI-4050 combined with one of the two approved drugs for the treatment of IPF (“Combi-1”) and was superior to that of those subjects treated with PBI-4050 combined with the other approved drug for the treatment of IPF (“Combi-2”).

      “PBI-4050, either used alone or in Combi-1, demonstrated very promising early indications of efficacy, considering that current drugs approved for IPF only slow (but do not reverse) the decline in lung respiratory function”, commented Dr. John Moran, Chief Medical Officer of ProMetic. “It is also important to note that during our clinical trial, there were no deaths nor did we see any subjects experiencing a decrease in FVC of 10% or more, contrary to the outcomes in the other IPF trials. There were no serious adverse events requiring PBI-4050’s discontinuation. The most frequent adverse event seen in all groups was diarrhea, but this was clearly much less significant in the subjects treated with PBI-4050 alone than in the groups receiving either of the currently approved drugs for the treatment of IPF, which are well-known for their significant side effect profiles”, added Dr. Moran.

      Pierre Laurin, ProMetic’s President and Chief Executive Officer commented: “These positive results support the rationale and clinical study design for the placebo controlled, pivotal Phase 2/3 IPF clinical trial we intend to initiate in Q2 2017. We expect to see PBI-4050, alone or in combination with one of the commercially approved IPF drugs, continue to outperform the current drugs in terms of efficacy, safety and tolerability”.

      The comparisons shown herein between the results in this study and other larger phase 3 clinical studies are only made to provide some provisional guidance in terms of the potential clinical benefits of PBI-4050 for IPF patients.

      Please note that the complete data set for ProMetic’s open label Phase 2 clinical trial will be presented at an upcoming pertinent scientific conference, notice of which will be given by the Corporation.

      Read more at http://www.stockhouse.com/news/press-releases/2017/02/22/prometic-s-pbi-4050-continues-to-demonstrate-early-evidence-of-efficacy#yGAaEMoLDpAipXhe.99

  2. Diann says:

    I began taking Esbriet two months after FDA released it, and it has literally saved my life. My lungs were in rapid decline, and I was not expected to live another three months, but thanks to Esbriet, my condition actually reversed for several months. Now, 29 months later, I am waiting for a lung transplant, which is something I would not have lived long enough to receive had Esbriet not been released when it was. I can’t say enough good things about this life-saving drug.

    • Jose Marques Lopes, PhD says:

      Dear Diann, I am very happy to read such good news. I hope everything goes well with your transplant.

        • Diann says:

          I would not combine this drug with anything else without the recommendation from my physician and/or the pharmaceutical company. My transplant team and the pharmacy need to know every prescription and supplement I take. I have changed my diet considerably, which has helped, but everyone should do that to eliminate sugar and white flour.

          I haven’t even participated in any trials that involve taking experimental drugs because I don’t want to mess up a good thing.

      • Diann says:

        Eileen, Medicare and my insurance covered most of it, and my physician had me complete a grant request in his office, which he submitted. The grant covered the co-pay for the first two years, and the pharmaceutical company has been working with me since then. A friend of ours was recently diagnosed after a lung biopsy, and he is in mitigation with his insurance company. When I heard the cost initially, I immediately dismissed it until my physician prescribed it. It is well worth fighting for!

    • Sophie says:

      Hello Diann,

      My dad has been taking Esbriet for a few weeks and he’s been experiencing many unpleasant side effects. Did you ever experience any in the beginning? Please share. He is a bit dicouraged.

      Thanks

      Sophie

      • Diann says:

        I’m so sorry your dad is experiencing difficulty, Sophie. I did experience nausea if I didn’t eat something with each dose. Initially, I had to eat something, take the dose, and then eat more–so literally take the dose in the middle of a meal. Also, I didn’t think I needed sun screen the first time I was in the sun, and my arms blistered so badly it took three months before they began to look decent again. Is your dad taking one initially, then two, and a while later, three at a time? If it helps, he could cut back to a previous amount and try that until his body stablizes. What other unpleasant side effects is he experiencing?

        I was very determined at the first that this was going to work because I had no other alternative. After a few months, I experienced no unpleasant side effects. Now, after having been on it for 2 1/2 years, I don’t even worry about sun screen if I’m going to be in the sun for a short period of time. I definitely wouldn’t push it, though.

        • Sophie says:

          Thank you for getting back to me.

          At the moment he is at two tablets at a time. Starting mid-week, will have to increase to three. Like you were, he is experiencing a decrease in apetite, nausea, reflux and stomach pain.
          Were you able to take anything for symptoms? Did you have any other than nausea?
          My dad has no other alternative. We also have an appointment with a medical team mid-June to discuss potential lung transplant. I shared your story with him and it gave him hope. Thank you so much!

  3. Barry Gauthier says:

    I’ve been on Esbriet for one month. Get my first liver test next week. So far, no problems. Don’t even notice that I’m taking the drug. Breathing has improved. Terrible cough is gone, but my stamina hasn’t returned.

Leave a Comment

Your email address will not be published. Required fields are marked *