PureTech Launches Phase 2 Trial of LYT-100 in IPF Patients
“We are excited to be taking this important step towards our goal of helping patients with this devastating condition,” Julie Krop, MD, PureTech’s chief medical officer, said in a press release.
The active agent in LYT-100, called deupirfenidone, is a chemically-modified version of the approved IPF treatment Esbriet (pirfenidone) marketed by Genentech. According to PureTech, LYT-100 was designed to achieve similar efficacy as Esbriet, but with a better tolerability profile, particularly in regards to gastrointestinal side effects that are common for patients on Esbriet.
“[Esbriet] has proven efficacy to slow the decline in lung function in patients with IPF,” said Kevin Flaherty, MD, an advisor to PureTech and a professor at the University of Michigan. “However, many patients with IPF who start [Esbriet] have side effects that cause them to either discontinue therapy or reduce their dose.”
LYT-100 was generally well-tolerated in a group of healthy volunteers who participated in a previous Phase 1 trial. A crossover study comparing LYT-100 with Esbriet in older healthy adults showed that markedly fewer participants on LYT-100 experienced gastrointestinal side effects.
“I am excited by the safety and tolerability data generated to date with LYT-100, particularly the most recent data demonstrating how well-tolerated it was in a relatively sick, older patient population with multiple comorbidities, as I believe it could represent great potential in patients with IPF,” Flaherty said.
The PureTech-funded Phase 2 trial, called ELEVATE (NCT05321420), seeks to enroll 240 adults with IPF, ages 40–80, who have not received previous treatment. The study is not yet recruiting participants.
Participants will be randomly assigned to one of four groups. One group will receive the approved dose of Esbriet (801 mg three times daily) and another will be given a placebo. Patients in the remaining two groups will receive one of two doses of LYT-100: either 550 mg three times a day, which is expected to lead to similar amounts of the medication in the body as the approved dose of Esbriet, or a higher dose of 825 mg three times daily.
“The unique profile of LYT-100, coupled with the established efficacy of [Esbriet], has the potential to significantly improve care for these patients,” Krop said. “We believe that enabling patients to stay on a therapeutic dose longer — even at a dose with comparable exposure to the FDA-approved dose of [Esbriet] — has the potential to drive better efficacy.”
“Achieving higher exposure levels than the FDA-approved dose of [Esbriet] has the potential to offer even better efficacy, which is our rationale for pursuing a higher dose of LYT-100 in this study,” she added.
The study’s main goal is to compare LYT-100 against a placebo in terms of effects on forced vital capacity (FVC) after 26 weeks of treatment. FVC is a common lung function parameter that measures how much air an individual can forcibly exhale after a deep breath. Safety-related outcomes will also be assessed, and exploratory analyses to compare the efficacy and safety of LYT-100 against Esbriet are planned.
Top-line results from the trial are expected by the end of 2023, according to PureTech.