16 April 2024
PureTech Health plc
PureTech Announces Completion of Enrollment in Phase 2b ELEVATE IPF Trial of LYT-100 (Deupirfenidone) in Idiopathic Pulmonary Fibrosis
Topline results are expected in Q4 2024
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, today announced that enrollment has been completed in the ELEVATE IPF Phase 2b clinical trial evaluating LYT-100 (deupirfenidone) in patients with idiopathic pulmonary fibrosis (IPF).
LYT-100 is a deuterated form of pirfenidone, which is one of the two standard-of-care treatments, along with nintedanib, approved to treat IPF. Both pirfenidone and nintedanib are efficacious but associated with significant tolerability issues, contributing to approximately 75 percent of people with IPF in the U.S. choosing to forego treatment.[1] LYT-100 is designed to address this unmet need by retaining the beneficial pharmacology and clinically-validated efficacy of pirfenidone with a highly differentiated pharmacokinetic (PK) profile. This PK profile and the resulting favorable tolerability have been demonstrated across multiple clinical trials in more than 400 individuals.
"Despite the severity and progressive nature of IPF, there has been a dearth of successful therapeutic innovation since the approvals of pirfenidone and nintedanib nearly a decade ago," said Toby Maher, M.D., Ph.D., Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine, University of Southern California, Los Angeles, and an investigator in the ELEVATE IPF trial. "LYT-100 builds on the established efficacy of pirfenidone, and data generated to date suggest it may address key tolerability issues that prevent patients from starting or continuing treatment. LYT-100 has the potential to have a profound impact on the way IPF is managed by allowing patients to start, continue and fully benefit from treatment, both as monotherapy and in combination settings with other antifibrotic therapies. This milestone in the ELEVATE IPF trial is very exciting, and I look forward to the full results as a potential step forward for the large, underserved IPF patient community."
The Phase 2b ELEVATE IPF trial is a randomized, double-blind, placebo-controlled, dose-finding study designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 in patients with IPF compared to placebo. The trial will also assess the relative efficacy of two doses of LYT-100. Participants have been randomized in a ratio of 1:1:1:1 to receive either 550 mg of LYT-100, 825 mg of LYT-100, pirfenidone or placebo three times a day (TID) for up to 26 weeks and includes an optional open-label extension. The primary endpoint is the rate of decline in Forced Vital Capacity (FVC) for the combined LYT-100 arms versus placebo over the 26-week treatment period using a prespecified Bayesian approach. Other key endpoints include tolerability measures, biomarkers and patient-reported outcomes. Both doses of LYT-100 will be compared to pirfenidone, though the trial is not powered to show a statistical difference in efficacy between LYT-100 and pirfenidone. Topline results are expected in the fourth quarter of 2024.
PureTech has previously shared data from a crossover trial showing that a 550 mg dose of LYT-100 provided bioequivalent drug exposure to the FDA-approved dose of pirfenidone, 801 mg. This dose also achieved an approximately 50 percent reduction in participants experiencing gastro-intestinal (GI) and central nervous system (CNS)-related adverse events (AEs) compared to those taking pirfenidone. Additionally, the data showed that a higher dose of LYT-100 (824 mg TID), which achieved a 43 percent higher drug exposure level, was well-tolerated with no additional incidence of GI or CNS AEs when titrated up from LYT-100 550 mg TID. These results reinforce the potential for LYT-100 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.[2] 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.
PureTech plans to pursue a streamlined development program for LYT-100 in IPF and is using the same validated endpoints that have supported past antifibrotic approvals. PureTech believes the results of the Phase 2b trial, together with an additional Phase 3 trial, could serve as the basis for registration in the U.S. and other geographies.
PureTech would like to extend its gratitude to those participating in the ELEVATE IPF trial, especially the people living with IPF and their caregivers, the clinical trial sites, investigators and advocacy groups.
About Idiopathic Pulmonary Fibrosis (IPF)
IPF is a rare, progressive and fatal lung disease with a median survival of 2-5 years.[3] Pirfenidone is one of only two drugs approved to treat IPF, and for those patients able to tolerate treatment, it has been shown to improve survival by approximately 2.5 years compared to supportive care alone.3 However, tolerability issues with both of the standard-of-care drugs result in patients discontinuing treatment or reducing their dose. This contributes to nearly three out of every four people with IPF choosing to forego treatment with these otherwise efficacious medicines.1
About LYT-100 (Deupirfenidone)
LYT-100 (deupirfenidone) is being advanced for the treatment of conditions involving inflammation and fibrosis, including IPF. It is a deuterated form of pirfenidone that is designed to retain the beneficial pharmacology and clinically-validated efficacy of pirfenidone with a highly differentiated PK profile. This PK profile has translated into favorable tolerability as demonstrated across multiple clinical studies in more than 400 individuals.
Pirfenidone is one of the two standard-of-care treatments approved for IPF, along with nintedanib, both of which are efficacious but associated with significant tolerability issues. These tolerability issues result in treatment discontinuations and/or dose reductions below the FDA-approved dose, thereby limiting the effectiveness of these otherwise efficacious medicines. With LYT-100, PureTech aims to deliver better outcomes for patients by enabling individuals to maintain the same or higher pirfenidone-equivalent doses for longer. PureTech believes LYT-100 has the potential both to supplant the current standard-of-care treatments and to serve a larger market of patients who are unable to tolerate current therapies.
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 28 therapeutics and therapeutic candidates, including two that have received both U.S. FDA clearance and European marketing authorization and a third (KarXT) that has been filed for FDA approval. A number of these programs are being advanced by PureTech or its Founded Entities in various indications and stages of clinical development, including registration enabling studies. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points.
For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh.
Cautionary Note Regarding Forward-Looking Statements
This press release contains statements that are or may be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation those related to the LYT-100 development program and development plans and the timing for results from ongoing clinical trials of LYT-100, and our future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.
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[1] Dempsey, T., Payne, S. C., Sangaralingham, L. R., Yao, X., Shah, N., & Limper, A. H. (2021). Adoption of the Antifibrotic Medications Pirfenidone and Nintedanib for Patients with Idiopathic Pulmonary Fibrosis. Annals of the American Thoracic Society, 18(7), 1121-1128. https://doi.org/10.1513/annalsats.202007-901oc
[2] King, T. E., Bradford, W. Z., Castro-Bernardini, S., Fagan, E. A., Glaspole, I., Glassberg, M. K., Gorina, E., Hopkins, P., Kardatzke, D., Lancaster, L., Lederer, D. J., Nathan, S. D., De Castro Pereira, C. A., Sahn, S. A., Sussman, R., Swigris, J. J., & Noble, P. W. (2014). A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. The New England Journal of Medicine, 370(22), 2083-2092. https://doi.org/10.1056/nejmoa1402582
[3] Fisher, M., Nathan, S. D., Hill, C., Marshall, J., Dejonckheere, F., Thuresson, P., & Maher, T. M. (2017). Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis. Journal of Managed Care & Specialty Pharmacy, 23(3-b Suppl), S17-S24. https://doi.org/10.18553/jmcp.2017.23.3-b.s17
