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.,
Sk�ld, 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).
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220105006009/en/
PureTech Public Relations
publicrelations@puretechealth.com Investor Relations
IR@puretechhealth.com
U.S. Media Nichole Sarkis +1 774 278 8273
nichole@tenbridgecommunications.com
PureTech Health (NASDAQ:PRTC)
Graphique Historique de l'Action
De Juin 2024 à Juil 2024
PureTech Health (NASDAQ:PRTC)
Graphique Historique de l'Action
De Juil 2023 à Juil 2024