The first two approved therapies for idiopathic pulmonary fibrosis (IPF), Genentech’s Esbriet (pirfenidone) and Boehringer Ingelheim’s Ofev (nintedanib), are still the most reliable treatments among several approved and experimental therapies, according to a comparison study featured in the journal Pharmacometrics & Systems Pharmacology.
Since the U.S. FDA’s approval of these two IPF therapies in 2014, the overall treatment landscape for the illness has changed dramatically. Although many new therapies have been in development and evaluated in clinical trials, a lack of direct comparison with the approved treatments makes it harder to identify possible advantages of other investigational medicines.
Finding ways to compare available data from clinical trials for approved and in-development therapies is important for improving future patient trials and for accurately evaluating the new therapies, researchers said.
In the study titled, “Model-based Meta-Analysis on the Efficacy of Pharmacological Treatments for Idiopathic Pulmonary Fibrosis,” researchers from Bristol-Myers Squibb in collaboration with Quantitative Solutions used a model-based meta-analysis to create a database of combined clinical trial data to assess the effectiveness of different IPF therapies.
The research team compiled data from several treatments and 4,919 participants in 20 clinical trials for both approved and unapproved IPF therapies. They compared the treatments’ effectiveness based on change from baseline of percent predicted forced vital capacity (FVC, which measures lung function) for 14 different IPF drugs, including Esbriet and Ofev.
Results showed that the already approved therapies offered more reliable and positive results. Esbriet, at the recommended dose of 2403 mg/day, was found to be more effective than 300 mg/day of Ofev.
“In order to confirm these findings, a head-to-head comparison between pirfenidone and nintedanib is needed,” the authors wrote. “As more data are published based on administration of pirfenidone and nintedanib as marketed products, continuous enhancement of the database in the future could help improve the understanding of the efficacy responses of these two new standard-of-care pharmacotherapies.”
In addition, the analysis showed that the investigational therapy PRM-151, developed by Promedior, had a larger impact on lung function change than the other two. However, few studies are available on this therapy and additional data is needed to confirm its reliability.
PBI-4050 is better than both drugs by Prometic life sciences
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.
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.
LAVAL, QUEBEC, CANADA, – April 18, 2017 – Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (“Prometic” or the “Corporation”) announced today that it has received concurrence from the US Food and Drug Administration (“FDA”) on the design of the first of its PBI-4050’s planned phase 2/3 clinical trials for IPF based on the efficacy data generated in the recently completed 40 patient Phase 2 open-label study.
In that phase 2 study, PBI-4050 was given for 12 weeks to patients who were receiving pirfenidone, nintedanib, or neither agent. The results of the study showed that the Forced Vital Capacity (FVC) remained stable in patients on PBI-4050 alone (n=9, FVC -12 ml) or in patients on PBI-4050 in combination with nintedanib (n=15, FVC +2 ml). In contrast, the results of said study showed that the FVC declined significantly in patients on 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 that received the PBI-4050 and pirfenidone combination, suggesting a drug-drug interaction.
Dr. John Moran, Chief Medical Officer of Prometic commented: “This early evidence of efficacy observed with PBI-4050 alone or in combination with nintedanib points toward very promising treatment options that will be further tested in two separate phase 2/3 clinical trials. We are very pleased that the FDA concurs with our decision to exclude a combined pirfenidone and PBI-4050 treatment arm in the upcoming phase 2/3 add-on study”.
The design for the add-on placebo-controlled phase 2/3 pivotal trial will therefore be an amended version of the protocol the FDA originally requested during the pre-IND meeting: IPF patients currently treated with nintedanib would be randomized to receive in addition either PBI-4050 or a placebo.
Prometic also intends to initiate a second phase 2/3 placebo-controlled trial which would enroll IPF patients who have failed to tolerate nintedanib or pirfenidone and would be randomized to receive either PBI-4050 or placebo, (“PBI-4050 Monotherapy”).
“To date, PBI-4050 has presented a remarkable safety and tolerability profile throughout all clinical trials”, said Mr. Pierre Laurin, President and Chief Executive Officer of Prometic. “We are also very pleased that our phase 2 open label study in IPF patients has served the very important strategic purpose of allowing us to optimize the design of our pivotal clinical program for this devastating medical condition”.
Sent a email to the author Alice Melao stating her lack of Due Diligence on the topic and clinical trials was not professional.
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FDA Agrees with ProMetic’s Protocol for PBI-4050 in IPF Clinical Trials
Dear Ric,
Thank you for your interest on our website. I just wanted to clarify that in this story I just want to transmit the data and main conclusion of the study mentioned in the story, which compared several IPF treatments. The conclusions here presented are from the authors of the study and not from myself. If you take a look in the original study you can see that the medicine you are mentioning (PBI-4050) was not included in the analysis, and maybe other potential therapies are also missing.
I hope this could help clarify any issue regarding reliability of the information published.
Its very important to have all the facts . There are only a handful of clinical studies regarding IPF that have gone head to head with the other two drugs . It’s amazing that Prometic with there PBI-4050 clinical trial results could be over looked or intentionally over looked . People’s lives are at stake . Thank you Alice for getting back to me and in the future there should no reason to be omitting Prometic and there PBI-4050 .
Ric
Hello, when will this new treatment be available in Quebec?
PROMETIC RECEIVES FAST TRACK DESIGNATION FOR PBI-4050 IN DEVELOPMENT FOR IDIOPATHIC PULMONARY FIBROSIS (IPF)
Fast track designation follows recent FDA approval of pivotal Phase 2/3 clinical trial in IPF
LAVAL, QUEBEC, CANADA – Oct. 25, 2017 – Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to PBI-4050, a clinical candidate in development for idiopathic pulmonary fibrosis (IPF). The Fast Track designation follows the FDA’s recent approval of Prometic’s Investigational New Drug (IND) application and design of the pivotal Phase 2/3 clinical trial in patients with IPF.
“The treatment options for patients with fibrotic diseases like IPF are limited in scope and effectiveness,” said Pierre Laurin, president and chief executive officer of Prometic. “Fast Track designation will allow us to advance PBI-4050 and seek to potentially gain approval in a more efficient process. PBI-4050 has the potential to provide patients with IPF a more effective treatment option. We look forward to demonstrating PBI-4050’s clinical efficacy and strong safety and tolerability profiles in a longer-term, placebo controlled trial.”
The FDA’s Fast Track program is designed to facilitate development and expedite review of drugs, with the main objective of getting important new drugs to patients earlier. Fast Track designation drugs are also eligible for an accelerated approval and priority review, thereby expediting the FDA’s review process. To gain Fast Track designation when there are existing available therapies, a potential new therapy must show an advantage over other currently available treatments, such as showing superior efficacy, an improved side effect profile, decreasing toxicity or ability to address an unmet medical need.This is great news