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
16
December 2024
PureTech Health
plc
PureTech's Deupirfenidone
(LYT-100) Slowed Lung Function Decline in People with Idiopathic
Pulmonary Fibrosis (IPF) as Measured by Forced Vital Capacity
(FVC), Achieving the Primary and Key Secondary
Endpoints in the ELEVATE IPF Phase 2b Trial
Dose-ranging trial evaluated
deupirfenidone 550 mg three times a day (TID) (approximately
equivalent exposure to pirfenidone 801 mg TID[1]) 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 mL[2]; 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 decline[3] 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.
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
US
Media
Justin Chen
+1-609-578-7230
jchen@tenbridgecommunications.com