Trial: LYT-100 better than Esbriet in slowing lung function decline in IPF
Fewer side effects seen with investigational therapy than approved one
The investigational therapy LYT-100 (deupirfenidone) significantly slowed lung function decline in people with idiopathic pulmonary fibrosis (IPF), outperforming the standard of care therapy Esbriet.
PureTech Health’s treatment candidate also caused fewer gastrointestinal side effects in patients.
That’s according to top-line data from the ongoing Phase 2b ELEVATE IPF trial (NCT05321420), which compared LYT-100 to Esbriet (pirfenidone) in more than 200 IPF patients globally.
“These are extremely exciting results from a Phase 2b trial, and I am very enthusiastic about the continued development of [LYT-100],” Toby Maher, MD, PhD, trial investigator and professor at the Keck School of Medicine of the University of Southern California, Los Angeles, said in a company press release.
Maher noted that the treatment effects seen with LYT-100 were about 50% greater than what was seen with Esbriet use.
“[LYT-100] has the potential to offer patients a highly effective and tolerable treatment option,” Maher said.
Gastrointestinal side effects limit the use of approved IPF therapies
IPF is a progressive disease characterized by scarring, or fibrosis, of the lungs, which leads to symptoms such as shortness of breath and a dry, hacking cough. It’s called idiopathic because the exact cause is unknown.
Esbriet and Ofev (nintedanib) are approved IPF therapies that are known to slow lung function decline. However, associated gastrointestinal side effects limit their use.
LYT-100 is a modified version of Esbriet’s active ingredient, pirfenidone, that’s designed to retain the approved therapy’s antifibrotic and anti-inflammatory efficacy, while having a better safety profile, according to PureTech.
“The adoption and adherence of currently approved antifibrotics has been limited by a tradeoff between efficacy and tolerability, specifically related to gastrointestinal adverse events,” said Eric Elenko, PhD, PureTech’s president and cofounder. “This prevents many patients from initiating treatment or maintaining optimal therapeutic doses and, in turn, achieving the best possible outcomes.”
In ELEVATE IPF, which enrolled 257 patients, ages 40 and older, participants were randomly assigned to receive LYT-100, Esbriet, or a placebo three times daily (TID) for 26 weeks, or about six months. The trial tested two doses of LYT-100 — 550 and 825 mg — while Esbriet was given at a dose of 801 mg. A total of 187 participants completed the trial
Its main goal was to assess changes in lung function using forced vital capacity (FVC), the total amount of air (in mL) an individual can forcibly exhale after taking a deep breath.
According to Maher, “the ELEVATE IPF trial broke new ground in Phase 2 trial design in IPF; this was the first time that a new therapy (deupirfenidone) has been evaluated alongside one of the two existing standard-of-care treatments (pirfenidone).”
LYT-100 shows safety, efficacy for treating IPF in global Phase 2b trial
According to top-line data announced by PureTech, nearly six months of treatment with 825 mg LYT-100 significantly slowed lung function decline by 80.9% compared with the placebo (-21.5 vs. -112.5 mL). For reference, the six-month natural decline in lung function expected in healthy adults older than 60 is about -15.0 to -25.0 mL, according to the company.
In comparison, the standard dose of Esbriet slowed lung function decline when compared with the placebo, but with an efficacy of 54.1% (-51.6 vs. -112.5 mL).
The lower 550 mg dose of LYT-100 also showed efficacy against the placebo (-80.7 vs. -112.5 mL), but the difference was not considered to be statistically significant. Still, a dose-response of LYT-100 was demonstrated.
“[LYT-100] 825 mg TID reduced lung function decline to near-physiologic levels over 26 weeks and had an effect size, compared with placebo, that was approximately 50% greater than that seen with [Esbriet],” Maher said.
When reported as FVC percent predicted (FVCpp), which normalized the results based on the patients’ ages, sex, height, and race, 825 mg of LYT-100 significantly slowed lung decline by 3% compared with the placebo. Reductions in FVCpp were also seen for the lower 550 mg dose (1.62%), and for Esbriet (1.97%) in comparison with the placebo.
I could not be more pleased that [LYT-100] showed a favorable tolerability profile at both doses evaluated and — most importantly — has demonstrated the potential to offer patients enhanced efficacy at the higher dose.
Both doses of LYT-100 were generally well-tolerated throughout the trial. In particular, fewer gastrointestinal side effects were reported in patients treated with 825 mg of LYT-100 than in those given 801 mg of Esbriet. This was seen for measures of nausea (20.3% vs. 27.0%), indigestion (14.1% vs. 22.2%), diarrhea (7.8% vs. 11.1%), constipation (4.7% vs. 6.3%), and vomiting (1.6% vs. 3.2%). Abdominal pain was the only side effect that was more common with LYT-100 than with Esbriet (14.1% vs. 7.9%).
Elenko touted the trial results, noting the therapy’s effectiveness.
“I could not be more pleased that [LYT-100] showed a favorable tolerability profile at both doses evaluated and — most importantly — has demonstrated the potential to offer patients enhanced efficacy at the higher dose,” Elenko said.
More than 90% of the participants who completed ELEVATE IPF have enrolled in an ongoing open-label extension (OLE) study evaluating both LYT-100 doses. So far, early data showed a durable treatment effect and a consistent tolerability profile at the 825 mg dose, according to PureTech.
“These data are remarkable, particularly for a monotherapy, and — if supported by a Phase 3 trial — would represent a step change in the treatment of IPF,” said Bharatt Chowrira, PhD, CEO of PureTech. “On behalf of the entire PureTech team, I extend my sincere gratitude to the people living with IPF, their caregivers, the clinical trial investigators and advocacy groups as well as our talented team for supporting this mission.”
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