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.
Contact:
PureTech
Public Relations
publicrelations@puretechhealth.com
Investor Relations
IR@puretechhealth.com
UK/EU Media
Ben Atwell, Rob Winder
+44 (0) 20 3727 1000
puretech@fticonsulting.com
U.S. Media
Nichole Bobbyn
+1 774 278 8273
nichole@tenbridgecommunications.com
[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