Phase 3 Trial Planned for PBI-4050, Potential Treatment for Mild-to-Moderate IPF Patients

Phase 3 Trial Planned for PBI-4050, Potential Treatment for Mild-to-Moderate IPF Patients

A pivotal Phase 3 trial evaluating PBI-4050, a potential treatment of idiopathic pulmonary fibrosis, will be open to all patients with mild-to-moderate IPF regardless of whether they are also taking Ofev (nintedanib) or not, the therapy’s developer, Prometic Life Sciences, announced.

The trial, in other words, will evaluate the efficacy and safety of PBI-4050 as a standalone therapy and as an add-on treatment to Ofev. IPF patients using Esbriet (pirfenidone), however, will be excluded from enrolling, as previous studies have reported a drug-drug interaction between Esbriet and PBI-4050.

Design of this Phase 3 trial came through an agreement between Prometic and the U.S. Food and Drug Administration (FDA), the company announced in its press release.

“The recommendations provided by the FDA will allow us to conduct a clinical trial that is much more reflective of current treatment of IPF patients,” said Joseph Parker, senior director, Prometic clinical affairs, who is overseeing the study.

“This is going to be a multinational study, involving an experienced CRO [contract research organization] in the field to help manage multiple sites across the United States, Canada, Australia, the U.K. and Europe,” Parker said.

Prometic is hoping to begin enrolling eligible patients by mid-2018.

Participants will be randomized to receive orally 800 mg or 1200 mg of PBI-4050 or placebo for up to 52 weeks. The trial will evaluate its potential to slow lung function decline, determined as the annual rate of decline in forced vital capacity (FVC; the total amount of air exhaled during a forced breath). An interim analysis will be conducted after 26 weeks of treatment.

A Phase 2 study (NCT02538536) in 40 IPF patients reported a stabilization in lung function among those given PBI-4050 as a stand-alone therapy or in combination with Ofev after 12 weeks of treatment, while a significant further decline was seen in those taking PBI-4050 plus Esbriet.

Prometic is also developing Ryplazim (plasminogen) to manage acute exacerbation episodes in the lungs of IPF patients.

PBI-4050 has been designated an orphan drug, a status that works to advance its development, as a potential IPF treatment by both the FDA and the European Medicines Agency. Ryplazim received orphan drug designation for IPF by the FDA in December 2017.

 

14 comments

  1. Ric ellens says:

    re-listened to Wednesday’s webcast and I understood indirectly that Fibrogen was out of the race for IPF and could offer at the best a complement to existing therapies. I also understood that Prometic has a leading compound…better than Nintedanib!

    Let me explain: Fibrogen compound (FG-3019) targets only the CTGF (connecting tissue growth factor) while the PBI-4050 targets the CTGF and several other factors at once. This is specifically what Dr. Martin Kolb likes about PBI-4050, it attacks on several pathways and even more than Nintedanib who does it on 7 to 8 ways. So, even if FG-3019 has been successful in PH2 clinical trials, it is specifically because it has been given in combination with Nintedanib and Pirfenidone. Their study was designed this way, for patients who already are receiving one of the two drugs available. So, if the FG-3019 is not administered alone, as the PBI-4050 was in PH2 and will be in PH3, it will not be able to become the “Standard of Care” and surpass the results of its competitors. At the best it will become a well-tolerated supplement.

    Regarding the future of IPF, PBI-4050, Ryplazim, Nintedanib and Pirfenidone, this is what Dr. Martin Kolb had to say Wednesday:

    «I am a physician scientist, I work with a lot of different companies, I have a research lab, I do basic science, I do animal models and mechanism of disease, I also have a large clinic and follow about 1000 patients with different fibrotic lung diseases, about 250 of them are on the approved drugs, so I think I know what patients need and what we, as a community, need to make this disease better. » (I think this sets how credible he is.)

    «I’m pretty sure that in 15 or 20 years we’ll have different color pill that stop IPF and other chronic diseases and this is why we are working so hard» (He means that the solution for treating IPF will be a drug cocktail, not a miracle one, like we see now for AIDS)

    « Those 2 drugs (Nintedanib and Pirfenidone) they don’t stop the disease, they slow it down, they have very comparable effects, but they have a very different side effect profile, so when I see a patient, I give them the choice, will you pick diarrhoea or vomiting? »

    «The side effect spectrum is really what determines, in my clinic, the choice of a drug. »

    « We know that just about a third of all patients with IPF are actually on one of these drugs because they hesitate. » (Between diarrhoea and vomiting, 2/3 choose none)

    « Patients have a lot of comorbidities as well and they make it challenging to tolerate high effect rich drugs (…) that’s another reason for looking at something that is much better tolerated. » (Phase 2 trial of PBI-4050: Very well tolerated whether used alone or in combination. Most TEAE was diarrhoea, with the lowest frequency in the PBI-4050 alone group)

    « There’s a few posters presented on meetings (about PBI-4050) I’ve seen the stuff, that looks pretty cool and what this drug does, it interferes with a lot of different pathways (…) and we know from the research that folks at Prometic have done is that this molecule interferes with a lot of them. » (Meaning that if the drug targets only one pathway, the disease will overcome the treatment…so that’s not the case for PBI-4050 witch targets multiple pathways)

    « If you have these chronic disrupting diseases (like IPF), you want to have 2 strategies, stop the destruction and support the rebuilt, and PBI-4050 is active in both of these things. » (I will copy a part of the Prometic corporate presentation: The biology of healing: We are the company that can effectively address the entire healing process in a groundbreaking way using both small molecule drugs and plasma protein therapies.)

    « As a scientist I want to read about: what does a drug do? When I talk to my fellow expert in the field they don’t know much about PBI-4050, because there’s not much published. » (The MOA will be publish starting mid-February. There will be 15 to 18 publications in scientific journals. 15 to 18? What do we need to understand? That PBI-4050 interacts against fibrosis on 15 to 18 pathways? Simple speculation here.)

    To conclude, Prometic has a lot to offer! There’s no doubt in my mind that PBI-4050 will become the standard of care, because of its efficacy but mainly for its safety profile! People with IPF will have choice between: diarrhoea, vomiting or PBI-4050! Really? It’s becoming obvious that Prometic has the lead in the race. Let’s wait and see! That’s my bet.

    GLTA

    • Michael Donoghue says:

      I do not understand your arguement, or rather lack of arguement. You claim to be a scientist but accept as fact the possible benefits of a new drug before it has been proven! There is many a slip … ,which is why properly regulated trials with actual patients will be carried out. Side effects can be discovered in such trials, but sometimes only after patients have taken the medicine over a longer period. On what basis do you assume this drug will not have any?

      Finally you conclude that it will supercede both Nintedanib and Pirfenidone – because? You yourself postulate that any significant breakthrough is likely to be a cocktail or combination of drugs. Which is why the trial will include both this drug alone and in combination with Nintedanib. As your “fellow experts” say, little has been published about this drug so comment is premature!

      Of course, I would love PBI-4050 to be a breakthrough and a lifesaver for such as me but, sorry, your unscientific, PR standard, over optimistic article does not help.

  2. Donnie says:

    I feel the same way as reader above feel.But what ifyour not taking ofev or anything else what does. Your drug do to a person stop ipf or reverse and heal ipf Which doesit do?

  3. Ray Coak says:

    I have been on OFEV for 14 months. I was diagnosed Dec 2016 with IFP. Smoker 55 years. I feel great and exercise 20 hrs a week. Would like to be considered for the focus group

  4. Raymond King says:

    I am just now going to be put on Esbriet (pirfenidone) through Speciality CVS Pharmacy and read your article. To get the above drug, I had to go through my Pulmonologist to get them. Would I have to go back to him to have your drug prescribed?
    Also, can I qualify for your trial?
    What forms do I need to sign up and how do I get them?
    I am 83 years old and the IPF was discovered a couple of years ago. So far I have just been taking Benzonatate and Hydrocodine for the cough and chest pains. I haven’t yet been delivered my pirfenidone.

  5. Toni Brown says:

    My family has been diagnosed with ipf, 5 siblings, 2 have passed away recently in early 50s-67. Another one on transplant list, I have just been diagnosed with some scarring from ct scan. 5th sibling has some breathing issues. This a terrible disease, and my family needs help. I pray the new drugs will help.

  6. Evelyn Neber says:

    I was just diagnosed with IPF though I have probably been experiencing its effects for at least a year. Would like to partake in your PBI-4050 study. Would also be interested in research studies and outcomes regarding the incidence of this disease among cohort groups and the best longevity outcomes known thus far among such groups. Thank you for your consideration to my quest.
    Best Regards

  7. Patrick Schuette says:

    How does one get included in this trial? I have been diagnosed with UIP, a form of IPF. I am not taking any current approved drugs. I should be an excellent addition for this study.

  8. Lyndon D. McLaughlin says:

    I was diagnosed with ipf in 2012. Today I am on 5liters of oxygen when up and moving around. 3 1/2 when sitting and sleeping. They say I qualify for a double lung transplant. I just don’t think I can bring myself to swap one desease for another. I’m a very healthy 62 year old other than my lungs. If you can see fit I would be very willing to try this drug. Thank you.

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