TIDMPRTC
PureTech Health PLC
06 January 2022
6 January 2022
PureTech Health plc
PureTech's LYT-100 (Deupirfenidone) Achieves 50% Reduction in
Healthy Older Adults Experiencing GI-Related Adverse Events
Compared to Pirfenidone
PureTech to initiate registration-enabling studies with LYT-100
for the treatment of IPF with a streamlined 505(b)(2) development
path that includes a dose-ranging study in IPF patients and a Phase
3 study in IPF patients
Veteran IPF and pulmonary drug development expert, Paul Ford,
M.D., Ph.D., joins PureTech as SVP Clinical Development to lead
this program
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to
discovering, developing and commercializing highly differentiated
medicines for devastating diseases, today announced results from a
randomized, double-blind crossover study in healthy older adults
demonstrating that approximately 50% fewer subjects treated with
PureTech's LYT-100 (deupirfenidone) experienced gastrointestinal
(GI)-related adverse events (AEs) compared to subjects treated with
pirfenidone (17.4% vs. 34.0%). Pirfenidone is approved by the U.S.
Food and Drug Administration (FDA) for the treatment of idiopathic
pulmonary fibrosis (IPF), an orphan disease that is chronic and
progressive resulting in significant morbidity and mortality. Based
on these results, additional data generated from PureTech's robust
LYT-100 clinical program and recent regulatory feedback, the
Company intends to advance LYT-100 into late-stage clinical
development for the treatment of IPF, beginning with a dose-ranging
study evaluating six months of treatment with LYT-100 initiating in
the first half of 2022. PureTech believes the results of this
study, together with a Phase 3 study, could serve as the basis for
registration in the U.S.
LYT-100 is a selectively deuterated form of pirfenidone that is
designed to retain the potent and clinically-validated
anti-fibrotic and anti-inflammatory activity of pirfenidone with a
differentiated pharmacokinetic profile that has translated into
favorable tolerability, as demonstrated by data from multiple human
clinical studies. 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 GI-related
tolerability issues.(1,2) Tolerability issues associated with
pirfenidone result in treatment discontinuations and/or dose
reductions below the FDA-approved dose of 801 mg three times a day
(TID), thereby limiting its effectiveness in patients with
IPF.(1)
" In the recently completed healthy older adult study, LYT-100
administration resulted in a clinically meaningful 50% reduction in
the number of healthy older adults experiencing GI-related adverse
events, compared to pirfenidone. This underscores the potential of
LYT-100 to address a significant unmet need for patients with IPF
by offering a more tolerable treatment option that may allow
patients to continue on therapy, which is critical to address this
serious condition," said Julie Krop, M.D., Chief Medical Officer of
PureTech. "The ability to pursue a 505(b)(2) development path for
LYT-100 based on the validated biology and known clinical benefits
of pirfenidone significantly de-risks our path to approval and has
the potential to make this important therapy available to patients
faster."
Based on a recently published observational study and
independent market research, only about 26% of IPF patients are
treated with the current standard of care treatments despite their
proven efficacy.(3) This suggests that a vast majority of IPF
patients are not currently being treated, and further supports the
significant need for new, tolerable treatment options. A previous
clinical study comparing a lower dose of pirfenidone than the
FDA-approved dose noted a dose-efficacy response, but whether doses
higher than the marketed dose can achieve increased efficacy has
not been adequately explored in patients with IPF. In the upcoming
dose-ranging study, PureTech also plans to investigate LYT-100 in
IPF patients at a dose with a higher total drug exposure than the
currently approved dose of pirfenidone to see if higher exposure
results in improved efficacy.
"Treatments that are both more effective and have fewer side
effects are urgently needed in the fight against IPF," said Toby
Maher, M.D., Ph.D., Professor of Medicine at Keck Medicine of USC
Academic Medical Center at the University of Southern California.
"LYT-100 builds on a wealth of existing clinical and biological
knowledge and incorporates a novel modification that has now
clearly been shown to improve tolerability and therefore treatment
compliance - both of which are critical to improving outcomes for
individuals with this chronic, progressive and inevitably fatal
disease."
The double-blind, randomized, crossover study evaluated the
tolerability of LYT-100 550 mg TID versus pirfenidone 801 mg TID in
49 healthy older adults aged 60-79, an age group consistent with
that of the IPF patient population. The dose of LYT-100 used in
this study was selected based on pharmacokinetics (PK) and modeling
data from prior studies, which together suggest that 550 mg TID
results in similar exposure levels achieved with 801 mg TID of
pirfenidone. The study showed that 38% fewer subjects treated with
LYT-100 experienced any AEs compared with those treated with
pirfenidone (30.4% vs. 48.9%) . Additionally , approximately 50%
fewer subjects experienced GI-related AEs with LYT-100 compared
with pirfenidone (17.4% vs. 34.0%) , most notably nausea (15.2%
with LYT-100 vs. 29.8% with pirfenidone), which is the most common
AE associated with pirfenidone. No serious AEs were reported in the
study, and there was one AE-related discontinuation in each arm.
Though not powered to show statistical significance, this study
provides evidence that LYT-100 has the potential to offer an
important tolerability advantage over pirfenidone and helps to
inform PureTech's development plans with this therapeutic candidate
in IPF.
Based on the data generated to date and discussions with the
FDA, PureTech plans to pursue a streamlined development program for
LYT-100 in IPF, capitalizing on efficiencies of the 505(b)(2)
pathway. The dose-ranging study, which is anticipated to begin in
the first half of 2022, will enroll approximately 250 treatment
naïve patients to evaluate LYT-100 efficacy relative to placebo and
compare relative tolerability and efficacy for pirfenidone. The
planned study will evaluate TID dosing of LYT-100 taken with meals.
The TID regimen is designed to reduce the maximal drug
concentration (Cmax), known to correlate with GI-related AEs with
pirfenidone, while maintaining the same or higher overall systemic
exposure (AUC) as pirfenidone. Pending positive clinical and
regulatory feedback, the program will advance into a Phase 3
study.
To oversee the LYT-100 development program in IPF, Paul Ford,
M.D., Ph.D., has joined PureTech as SVP of Clinical Development.
Dr. Ford is an experienced clinical pulmonologist with more than 20
years of research and development expertise dedicated to IPF and
other respiratory conditions. He has built and advanced programs
from early to late-stage development at companies including
Novartis, Galapagos and Galecto, and he has driven the recruitment
and randomization of nearly 1,500 patients with IPF across several
clinical studies.
"I am thrilled to be joining PureTech as we move LYT-100 into
late-stage clinical development for the treatment of IPF. The data
generated to date suggest LYT-100 may offer an important new
treatment option for patients who are not currently on therapy or
struggle to tolerate existing treatment options, which represent a
substantial portion of the IPF patient population," said Dr. Ford.
"I believe we have an efficient development path to support a
compelling registration-enabling package in our pursuit to improve
the treatment landscape for patients with IPF."
To date, LYT-100 has been studied in more than 400 subjects and
demonstrated a favorable safety profile as part of PureTech's
ongoing development work and indication prioritization. The company
has conducted multiple Phase 1 studies to further evaluate the PK,
dosing and tolerability of LYT-100 in healthy volunteers and
healthy older adults, the results of which have helped inform
PureTech's development plans in IPF. These studies, as well as
other ongoing studies, will also help to inform potential future
development plans in other indications beyond IPF.
About LYT-100
LYT-100 is PureTech's most advanced therapeutic candidate from
within its Wholly Owned Pipeline. A deuterated form of pirfenidone,
an approved anti-inflammatory and anti-fibrotic drug, LYT-100 is
being advanced for the potential treatment of conditions involving
inflammation and fibrosis, including lung disease (IPF and Long
COVID respiratory complications and related sequelae) and disorders
of lymphatic flow, such as lymphedema. PureTech is also exploring
the potential evaluation of LYT-100 in other inflammatory and
fibrotic conditions such as myocardial and other organ system
fibrosis based on the strength of existing clinical data around the
use of pirfenidone in these indications.
In the fourth quarter of 2020, PureTech initiated a Phase 2
study evaluating LYT-100 as a potential treatment for Long COVID
respiratory complications and related sequelae and a Phase 2a
proof-of-concept study evaluating LYT-100 in patients with breast
cancer-related, upper limb secondary lymphedema. Enrollment in the
Long COVID study is complete, and topline results are anticipated
in the first half of 2022. Topline results from the Phase 2a
proof-of-concept breast cancer-related, upper limb secondary
lymphedema study are anticipated in 2022. PureTech also expects to
initiate a Phase 2 dose-ranging trial of LYT-100 in patients with
IPF in the first half of 2022.
About Idiopathic Pulmonary Fibrosis (IPF)
Idiopathic Pulmonary Fibrosis (IPF) is an orphan condition that
is progressive and characterized by irreversible scarring of the
lungs that worsens over time and makes it difficult to breathe. The
prognosis of IPF is poor, with the median survival after diagnosis
generally estimated at two to five years. Currently available
treatment options are associated with significant tolerability
issues and dose-limiting toxicities, which can hamper treatment
compliance and leaves patients and physicians needing new treatment
options.
About the 505(b)(2) Regulatory Pathway
A 505(b)(2) is a type of New Drug Application (NDA) that a
company may submit to the U.S. Food and Drug Administration (FDA)
when seeking approval for an investigational therapeutic candidate.
This application type allows a company to submit some of the
required information based on studies not conducted by or for the
applicant, which is intended to avoid unnecessary duplication of
clinical studies and may therefore result in a less expensive
clinical program and potentially shorter development timeline as
compared to a traditional full NDA development path.
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated
to discovering, developing and commercializing highly
differentiated medicines for devastating diseases, including
inflammatory, fibrotic and immunological conditions, intractable
cancers, lymphatic and gastrointestinal diseases and neurological
and neuropsychological disorders, among others. The Company has
created a broad and deep pipeline through the expertise of its
experienced research and development team and its extensive network
of scientists, clinicians and industry leaders. This pipeline,
which is being advanced both internally and through PureTech's
Founded Entities, is comprised of 25 therapeutics and therapeutic
candidates, including two that have received both U.S. FDA
clearance and European marketing authorization, as of the date of
PureTech's most recently filed Half Year Report and corresponding
Form 6-K. 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 based on the Company's unique
insights into the biology of the brain, immune and gut, or BIG,
systems and the interface between those systems, referred to as the
BIG Axis.
For more information, visit www.puretechhealth.com or connect
with us on 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
those related to our initiation of registration-enabling studies
with LYT-100 for the treatment of IPF with a streamlined 505(b)(2)
development path and the design and timing for the initiation of
the dose-ranging and Phase 3 studies supporting the clinical
development of LYT-100 for IPF in accordance with our development
plan, our belief that the results of these studies could serve as
the basis for registration of LYT-100 in the United States, the
treatment potential of LYT-100, including its ability to address a
significant unmet need for patients with IPF and certain
shortcomings with respect to current standards of care,
expectations regarding the potential of clinical data to support
clinical development of LYT-100 for indications beyond IPF, the
timing for topline results from our current Phase 2 Long COVID
respiratory and 2a proof-of-concept breast cancer-related, upper
limb secondary lymphedema studies of LYT-100, our product
candidates and approach towards addressing major diseases, 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, 2020 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.
(1) Cottin, V., Koschel, D., Günther, A., Albera, C., Azuma, A.,
Sköld, C. M., Tomassetti, S., Hormel, P., Stauffer, J. L.,
Strombom, I., Kirchgaessler, K. U., & Maher, T. M. (2018).
Long-term safety of pirfenidone: results of the prospective,
observational PASSPORT study. ERJ open research, 4(4), 00084-2018.
https://doi.org/10.1183/23120541.00084-2018.
(2) Kato, M., Sasaki, S., Nakamura, T., Kurokawa, K., Yamada,
T., Ochi, Y., Ihara, H., Takahashi, F., & Takahashi, K. (2019).
Gastrointestinal adverse effects of nintedanib and the associated
risk factors in patients with idiopathic pulmonary fibrosis.
Scientific Reports, 9(1).
https://doi.org/10.1038/s41598-019-48593-4.
(3) Dempsey, T. M., Payne, S., Sangaralingham, L., Yao, X.,
Shah, N. D., & 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.
(4) Long COVID is a term being used to describe the emerging and
persistent complications following the resolution of COVID-19
infection, also known as post-acute COVID-19 syndrome (PACS).
Contact:
PureTech
Public Relations
publicrelations@puretechealth.com
Investor Relations
IR@puretechhealth.com
EU Media
Ben Atwell, Rob Winder
+44 (0) 20 3727 1000
ben.atwell@FTIconsulting.com
U.S. Media
Nichole Sarkis
+1 774 278 8273
nichole@tenbridgecommunications.com
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