PureTech Health plc, a clinical-stage biotherapeutics company, presented clinical data supporting the differentiated profile of LYT-100 (deupirfenidone), in development for the treatment of idiopathic pulmonary fibrosis (IPF), at the CHEST Annual Meeting in Honolulu, Hawaii.
The presentation expands on data from a completed trial of LYT-100 in healthy older adults, which informed the two doses selected for the ongoing, global phase 2b dose-ranging trial of LYT-100 (ELEVATE IPF) in patients with IPF. In addition to supporting the improved tolerability of LYT-100 versus the US Food and Drug Administration (FDA)-approved dose of pirfenidone, the data provide insights into the selection of the higher dose of LYT-100 that is also being evaluated in ELEVATE IPF.
The trial showed that a 550 mg dose of LYT-100 given three times daily (TID) provided bioequivalent drug exposure to the FDA-approved dose of pirfenidone, 801 mg TID. LYT-100 also demonstrated a 24% lower peak drug concentration than pirfenidone, which is a key factor generally associated with tolerability. As previously announced, this dose also achieved an approximately 50% reduction in participants experiencing gastrointestinal and central nervous system-related adverse events compared to those taking pirfenidone.
Additionally, the data showed that a higher dose of LYT-100 (824 mg TID), which achieved a 43% higher exposure level, was well-tolerated with no additional incidence of gastrointestinal or central nervous system-related adverse events when titrated up from LYT-100 550 mg TID in this trial, supporting the potential to provide enhanced efficacy with favorable tolerability in IPF.
This hypothesis is supported by phase 3 data with pirfenidone that showed a dose-response effect on forced vital capacity and survival in people with IPF. PureTech is therefore investigating the efficacy and tolerability of LYT-100 at 550 mg TID and 825 mg TID in the phase 2b ELEVATE IPF trial.
“These data highlight the potential for LYT-100 to improve both the treatment experience for people with IPF and, most importantly, enable them to stay on treatment longer and at an efficacious dose, which should improve their clinical outcomes,” says Julie Krop, MD, chief medical officer of PureTech Health, in a release. “Our goal with the ELEVATE IPF trial is to validate the ability of LYT-100 to deliver a more tolerable treatment with equivalent efficacy to pirfenidone at one dose while also exploring the potential for enhanced efficacy at a higher dose.”
LYT-100 is a deuterated form of pirfenidone that is designed to retain the beneficial pharmacology and clinically validated efficacy of pirfenidone with a highly differentiated pharmacokinetic profile. This profile has translated into favorable tolerability as demonstrated across multiple clinical studies in more than 400 individuals.
“Tolerability is a major challenge with the currently available IPF treatments, and it often results in both temporary and permanent dose reductions, premature discontinuation, and a reluctance for patients to even begin treatment,” says Toby Maher, MD, PhD, professor of medicine and director of interstitial lung disease at Keck School of Medicine, University of Southern California, Los Angeles, who presented the poster at CHEST and is an investigator in the ELEVATE IPF trial, in a release. “The unique profile of deupirfenidone may offer not only improved tolerability, but it also provides us with the opportunity to assess whether a higher dose is associated with improved efficacy—a strategy that has not been possible to test with pirfenidone due to its poor tolerability.
“This may benefit both patients currently taking standard-of-care antifibrotic drugs as well as the 75% of people with IPF in the US who are not on treatment. The IPF treatment landscape is in desperate need of new therapeutic approaches that can be used either as monotherapies or as the backbone for combination therapy, and I look forward to the results of the ELEVATE IPF trial.”