Dose-ranging trial evaluated deupirfenidone 550
mg three times a day (TID) (approximately equivalent exposure to
pirfenidone 801 mg TID1) and deupirfenidone 825 mg TID and
successfully demonstrated dose-dependent response
Decline in lung function seen with
deupirfenidone 825 mg TID as a monotherapy was -21.5 mL; natural
lung function decline expected in healthy adults >60 years is
~-15 to ~-25 mL2; decline in lung function with pirfenidone 801 mg
TID was -51.6 mL
Deupirfenidone 825 mg TID showed strong,
consistent and durable efficacy with a treatment effect versus
placebo of 80.9% with favorable tolerability, while pirfenidone 801
mg TID had a 54.1% treatment effect versus placebo
Deupirfenidone was generally well-tolerated
with a favorable adverse event profile at both doses studied
Data support continued development of
deupirfenidone and highlight its potential to serve as a new
standard-of-care treatment for IPF
Company to host a webcast and conference call
today at 9:00am EST / 2:00pm GMT
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 positive results from ELEVATE IPF, a Phase 2b randomized,
double-blind, active- and placebo-controlled, dose-ranging trial
evaluating deupirfenidone (LYT-100) at two dose levels three times
a day (TID) over 26 weeks in patients with idiopathic pulmonary
fibrosis (IPF).
“The ELEVATE IPF trial broke new ground in Phase 2 trial design
in IPF; this was the first time that a new therapy (deupirfenidone)
has been evaluated alongside one of the two existing
standard-of-care treatments (pirfenidone),” 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 lead investigator in the ELEVATE IPF
trial. “Deupirfenidone 825 mg TID reduced lung function decline to
near-physiologic levels over 26 weeks and had an effect size,
compared with placebo, that was approximately 50% greater than that
seen with pirfenidone. Deupirfenidone has the potential to offer
patients a highly effective and tolerable treatment option. These
are extremely exciting results from a Phase 2b trial, and I am very
enthusiastic about the continued development of
deupirfenidone.”
Participants in the trial were randomized 1:1:1:1 to receive
deupirfenidone 550 mg, deupirfenidone 825 mg, pirfenidone 801 mg
(the FDA-approved dose), or placebo TID for 26 weeks, and had the
option to enroll in an ongoing, open-label extension study. The two
doses of deupirfenidone were chosen based on PureTech’s Phase 1
data, which showed that a 550 mg TID dose of deupirfenidone
provided approximately equivalent drug exposure to pirfenidone, 801
mg TID.1
The trial achieved its primary endpoint based on the
prespecified Bayesian analysis, with a 98.5% posterior probability.
This means there is a 98.5% probability that the pooled
deupirfenidone arms were superior to placebo in slowing the rate of
lung function decline in people with IPF, as measured by forced
vital capacity (FVC) at 26 weeks. The trial also successfully
demonstrated a dose-dependent response.
The rate of FVC decline3 at week 26 with:
- deupirfenidone 825 mg TID compared to placebo was statistically
significant (-21.5 mL vs. -112.5 mL, respectively; p=0.02)4 and
represents a robust treatment effect of 80.9% as a monotherapy; for
context, the level of six-month natural decline in lung function as
measured by FVC expected in healthy adults over 60 years old is
approximately -15.0 mL to -25.0 mL. 2
- pirfenidone 801 mg TID showed a treatment effect of 54.1%
compared to placebo (-51.6 mL vs. -112.5 mL, respectively), which
is consistent with previously reported pirfenidone clinical trial
data.5
The trial also achieved its key secondary endpoint based on a
prespecified Bayesian analysis, with a posterior probability of
99.6%. This means that there is a 99.6% probability that the pooled
deupirfenidone arms were superior to placebo in slowing the rate of
lung function decline in people with IPF, as measured by the forced
vital capacity percent predicted (FVCpp) from baseline to week 26.
While FVCpp and FVC (the primary endpoint) are both measures of
lung function, FVCpp accounts for key patient characteristics (age,
sex, height, race) and therefore normalizes the results at the
patient level. Deupirfenidone 825 mg TID also demonstrated a
benefit on this endpoint compared to placebo that was statistically
significant (-0.43 vs. -3.43, respectively; p=0.01),3,4 reinforcing
the robustness of the treatment's impact.
Placebo TID
(N=65)
Pirfenidone
801 mg TID
(N=61)
Deupirfenidone 550 mg TID
(N=65)
Deupirfenidone 825 mg TID
(N=63)
Change from Baseline in FVC (mL) over 26
Weeks (SE)
-112.5 (27.84)
-51.6 (29.13)
-80.7 (29.32)
-21.5 (28.86)
Difference in FVC (mL) vs. Placebo (95%
CI)
60.9
(-18.3, 140.0)
31.8
(-47.6, 111.2)
91.0†
(12.2, 169.7)
Change from Baseline in FVCpp (%) over 26
Weeks (SE)
-3.43 (0.842)
-1.46 (0.881)
-1.81 (0.886)
-0.43 (0.872)
Difference in FVCpp (%) vs. Placebo (95%
CI)
1.97
(-0.42, 4.37)
1.62
(-0.78, 4.02)
3.00†
(0.62, 5.38)
†Statistically significant at 0.05 level;
p values are two-sided and have not been corrected for
multiplicity.
Efficacy analyses used a random
coefficient regression model with absolute FVC or FVCpp including
baseline as response variable and week, treatment and interaction
between week and treatment as fixed effect. The analyses were
performed based on the predefined Full Analysis Set.
SE = standard error; CI = confidence
interval
“Our goal in developing deupirfenidone is to offer better
outcomes to people living with IPF. The adoption and adherence of
currently approved antifibrotics has been limited by a tradeoff
between efficacy and tolerability, specifically related to
gastrointestinal adverse events. This prevents many patients from
initiating treatment or maintaining optimal therapeutic doses and,
in turn, achieving the best possible outcomes,” said Eric Elenko,
Ph.D., President and Co-founder of PureTech. “I could not be more
pleased that deupirfenidone showed a favorable tolerability profile
at both doses evaluated and – most importantly – has demonstrated
the potential to offer patients enhanced efficacy at the higher
dose."
Both doses of deupirfenidone were generally well-tolerated in
the trial. The overall number of patients experiencing any
gastrointestinal (GI)-related adverse events (AEs) was similar
across the deupirfenidone 825 mg TID and pirfenidone 801 mg TID
arms. Deupirfenidone 825 mg TID demonstrated a favorable
tolerability profile compared to pirfenidone 801 mg TID, with a
lower percentage of patients reporting key GI AEs that occurred in
≥5% of participants in at least one arm: nausea (20.3% vs. 27.0%),
dyspepsia (14.1% vs. 22.2%), diarrhea (7.8% vs. 11.1%),
constipation (4.7% vs. 6.3%) and vomiting (1.6% vs. 3.2%). The only
key GI AE increase observed was abdominal pain (14.1% vs. 7.9%).
There were five deaths in the pirfenidone arm, two deaths in the
placebo arm and one death in each of the deupirfenidone arms. None
of the deaths was deemed to be treatment related.
Overall, 187 out of 257 patients completed the trial: 43 out of
63 patients in the pirfenidone 801 mg TID arm; 42 out of 65
patients in the deupirfenidone 550 mg TID arm; 50 out of 64
patients in the deupirfenidone 825 mg TID arm; and 52 of 65
patients in the placebo arm.
Of those who completed the trial, 170 patients (more than 90%)
opted to enroll in an ongoing open-label extension (OLE) evaluating
the two doses of deupirfenidone. To date, preliminary data support
a durable treatment effect and a consistent tolerability profile
with deupirfenidone 825 mg. Across the randomized trial and OLE,
the longest treatment duration with deupirfenidone 825 mg TID is 79
weeks and with deupirfenidone 550 mg TID is 81 weeks.
“These data are remarkable, particularly for a monotherapy, and
– if supported by a Phase 3 trial – would represent a step change
in the treatment of IPF,” said Bharatt Chowrira, Ph.D., J.D., CEO
of PureTech. “At PureTech, our approach is centered on identifying
simple and elegant solutions to big problems that underlie
tremendous patient need, and we are proud that our R&D engine
has generated another potentially transformative treatment. We are
committed to the rapid advancement of deupirfenidone, with the goal
of delivering a new standard of care to patients while generating
value for our shareholders. On behalf of the entire PureTech team,
I extend my sincere gratitude to the people living with IPF, their
caregivers, the clinical trial investigators and advocacy groups as
well as our talented team for supporting this mission.”
PureTech is committed to continuing development of
deupirfenidone and intends to discuss the Phase 2b results with
regulatory authorities to align on the appropriate path forward.
Additional data from this trial will be presented at a future
forum.
Webcast and Conference Call Details
Members of the PureTech management team will host a conference
call at 9:00am EST / 2:00pm GMT today, December 16, 2024, to
discuss these results. A live webcast and presentation slides will
be available on the investors section of PureTech's website under
the Events and Presentations tab. To join by phone, please
dial:
United Kingdom (Local): +44 20 3936 2999 United
Kingdom (Toll-Free): +44 800 358 1035 United States
(Local): +1 646 787 9445 United States (Toll-Free): +1
855 9796 654 International: +44 20 3936 2999 Access
Code: 860033
For those unable to listen to the call live, a replay will be
available on the PureTech website.
About the ELEVATE IPF Trial
The Phase 2b ELEVATE IPF trial was a randomized, double-blind,
active- and placebo-controlled, dose-ranging trial designed to
evaluate the efficacy, tolerability, safety and dosing regimen of
deupirfenidone (LYT-100) in patients with IPF compared to placebo.
257 participants were randomized in a ratio of 1:1:1:1 to receive
either 550 mg of deupirfenidone, 825 mg of deupirfenidone, 801 mg
pirfenidone or placebo three times a day (TID) for 26 weeks.
Participants who completed the trial had the option to enroll in an
open-label extension, which is ongoing.
The primary endpoint of the trial was the rate of decline in
Forced Vital Capacity (FVC) for the combined deupirfenidone arms
versus placebo over the 26-week treatment period. FVC is a measure
of the maximum amount of air (in mL) that an individual can
forcibly exhale after fully inhaling. It is a standard measurement
in clinical trials for IPF and is used to assess disease
progression as well as to predict mortality.
A prespecified Bayesian analysis was utilized to assess the
primary endpoint and provided a posterior probability, which is the
probability of a positive treatment difference for deupirfenidone
compared to placebo. This also allowed for augmentation of the
placebo arm with placebo data from historical IPF trials. This
approach enabled a more patient-centric clinical trial design by
minimizing the number of trial participants exposed to placebo—a
key consideration since IPF is progressive and fatal—while
delivering a robust, placebo-controlled dataset.
About Deupirfenidone
Deupirfenidone is a deuterated form of pirfenidone, which is one
of the two standard-of-care treatments approved to treat IPF, in
addition to nintedanib. Deuteration is intended to make
deupirfenidone break down more slowly in the body than
pirfenidone.
About Idiopathic Pulmonary Fibrosis (IPF)
IPF is a rare, progressive and fatal lung disease with a median
survival of 2-5 years.6 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.6 However, tolerability
issues with both of the standard-of-care medications result in
patients discontinuing treatment or reducing their dose. This
contributes to nearly three out of every four people with IPF in
the US not receiving treatment with these otherwise efficacious
medicines.7 There are over 232,000 people in the US and the EU5
countries (Italy, Spain, France, Germany and the United Kingdom)
living with IPF.8
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 29 therapeutics and therapeutic candidates,
including three that have been approved by the U.S. Food and Drug
Administration. 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 its potential benefits to patients,
plans for discussions with regulatory authorities, the further
development of the program, future presentation of additional data
from the trial 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, 2023, 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.
The information contained within this announcement is deemed by
the Company to constitute inside information as stipulated under
the Market Abuse Regulations (EU) No. 596/2014 which forms part of
UK domestic law by virtue of the European Union (Withdrawal) Act
2018 ('MAR'). Upon the publication of this announcement via a
Regulatory Information Service ('RIS'), this inside information is
now considered to be in the public domain.
_______________________ 1 Maher, T., Chen, M., Korth, C.,
Elenko, E., Harnett, M., Garg, V., Graham, C., Fares, W., Krop, J.
(2023). Deupirfenidone (LYT-100) dose-selection rationale for a
Phase 2b idiopathic pulmonary fibrosis study — ELEVATE IPF. Poster
presented at the CHEST Annual Meeting, Honolulu, HI. 2 FVC decline
at 6 months was estimated assuming linear decline over time.
Valenzuela, C., Bonella, F., Moor, C., Weimann, G., Miede, C.,
Stowasser, S., Maher, T. (2024). Decline in forced vital capacity
(FVC) in subjects with idiopathic pulmonary fibrosis (IPF) and
progressive pulmonary fibrosis (PPF) compared with healthy
references. Poster presented at the European Respiratory Society
International Congress, Vienna, Austria; and Luoto, J., Pihlsgård,
M., Wollmer, P., & Elmståhl, S. (2019). Relative and absolute
lung function change in a general population aged 60-102 years. The
European Respiratory Journal, 53(3), 1701812.
https://doi.org/10.1183/13993003.01812-2017 3 Efficacy analyses
used a random coefficient regression model with absolute FVC or
FVCpp including baseline as response variable and week, treatment
and interaction between week and treatment as fixed effect. The
analyses were performed based on the predefined Full Analysis Set.
4 All p values are two-sided and have not been corrected for
multiplicity. 5 Roche. (2014). Esbriet® (pirfenidone) prescribing
information. Retrieved from
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022535s000lbl.pdf
6 Fisher M, Nathan SD, Hill C, et al. Predicting Life Expectancy
for Pirfenidone in Idiopathic Pulmonary Fibrosis. J Manag Care Spec
Pharm. 2017;23(3-b Suppl):S17-S24.
doi:10.18553/jmcp.2017.23.3-b.s17 7 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 8 GlobalData
Epidemiology and Market Size Search, EU5=United Kingdom, France,
Germany, Italy and Spain
THIS ANNOUNCEMENT CONTAINS INSIDE INFORMATION FOR THE
PURPOSES OF ARTICLE 7 OF THE UK VERSION OF THE MARKET ABUSE
REGULATION (EU 596/ 2014) AS IT FORMS PART OF UK LAW BY VIRTUE OF
THE EUROPEAN UNION (WITHDRAWAL) ACT 2018, AS AMENDED
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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
US Media Justin Chen +1-609-578-7230
jchen@tenbridgecommunications.com
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