BridgeBio Pharma, Inc. (BridgeBio) (Nasdaq:BBIO) and Eidos
Therapeutics, Inc. (Eidos) (Nasdaq:EIDX), today presented positive
data from the companies’ ongoing Open Label Extension (OLE) of the
Phase 2 clinical trial studying AG10 in patients with symptomatic
transthyretin (TTR) amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM
is a progressive and fatal disease that is an under recognized
cause of heart failure. The data were presented in a late-breaking
featured science oral presentation at the American Heart
Association (AHA) Scientific Sessions in Philadelphia,
Pennsylvania.
Study participants received 800mg of AG10 twice daily during the
OLE and were followed for a median of 65 weeks since Phase 2
initiation. AG10 treatment was generally well-tolerated and
resulted in near-complete TTR stabilization as measured using
established ex vivo assays. Lower rates of mortality (death or
cardiac transplantation) and cardiovascular-related
hospitalizations were observed in AG10 Phase 2 OLE participants
than were reported in a similar population of ATTR-CM patients who
received placebo for 15 months in the ATTR-ACT study. Cardiac
biomarkers and echocardiographic parameters were stable in patients
treated with AG10 in the Phase 2 OLE.
“This update from our Phase 2 OLE demonstrated continued
tolerability of AG10 in patients with advanced ATTR-CM. We also
observed meaningfully lower rates of mortality and cardiovascular
hospitalizations than what would be expected for untreated ATTR-CM
patients with similar disease severity,” said Jonathan Fox, M.D.,
PhD., FACC, president and chief medical officer of Eidos. “These
encouraging data continue to support the development of AG10 as a
potentially best-in-class treatment for ATTR-CM patients.”
AG10 Phase 2 Open Label Extension Results
The ongoing OLE study enrolled 47 of 49 participants (96%) from
the 28-day randomized, placebo-controlled, Phase 2 study of AG10 in
ATTR-CM patients with New York Heart Association (NYHA) Class II or
III symptoms. Interim analysis of the ongoing study was completed
on August 31, 2019 in conjunction with annual regulatory reporting
and review, at which time 41 participants remained in the study.
Three (6.4%) participants in the OLE had died, two due to disease
progression and one due to cervical cancer. Three (6.4%) additional
patients enrolled in the study had discontinued treatment,
including one participant who underwent cardiac transplantation for
their disease.
- Adverse events reported in the OLE study were generally
consistent with the underlying ATTR-CM disease state and no safety
signals of potential clinical concern were associated with the
administration of AG10 in the study. Forty-six (97.9%) patients
experienced a treatment-emergent adverse event reported during the
study, with falls, congestive cardiac failure, dyspnea, and acute
kidney injury the most commonly reported adverse events. Nineteen
(40.4%) participants experienced a treatment-emergent serious
adverse event reported during the study, with congestive cardiac
failure (10.6%) and acute kidney injury (8.5%) the most commonly
reported serious adverse events.
- The rate of all-cause mortality (including either death or
cardiac transplantation, 8.5%) and cardiovascular-related
hospitalizations (25.5%) observed in an exploratory analysis of
participants in this study following a median of 15 months since
Phase 2 initiation were lower than those observed at 15 months in
placebo-treated patients in the ATTR-ACT study (all-cause mortality
including death or cardiac transplantation, 15.3%;
cardiovascular-related hospitalizations, 41.8%).
- Stabilization of TTR, as measured using established ex vivo
assays, was maintained >90% on average at all study visits in
actively treated patients.
- Serum TTR levels, a prognostic indicator of survival in a
published cohort of wild-type ATTR-CM patients, were elevated upon
AG10 treatment and were maintained in the normal range throughout
the study duration. Mean serum TTR levels were increased from
baseline by 39% and 68% in wild-type and variant-carrying ATTR-CM
patients, respectively, at OLE Visit Day 180.
- Cardiac biomarkers and echocardiographic parameters were stable
during the OLE study. NT-proBNP and TnI were unchanged throughout
the course of the study. Echocardiographic parameters, including
left ventricular mass and left ventricular stroke volume index,
were unchanged during the study.
The presentation of the Phase 2 open label extension data from
the American Heart Association (AHA) Scientific Sessions will be
available on the company website (eidostx.com and
bridgebio.com).
A Phase 3 study of AG10 in ATTR-CM patients (ATTRibute-CM) is
currently ongoing. In Part A of the study, change in six-minute
walk distance at 12 months will be compared between active
treatment and placebo groups as the first registrational primary
endpoint. In Part B, all-cause mortality and frequency of
cardiovascular-related hospitalizations will be compared between
treatment and control groups at 30 months total duration. In Part
B, concomitant use of therapies indicated for the treatment of
ATTR-CM may be allowed. The study is enrolling at 44 sites across
six countries and enrollment for Part A is now projected to
complete in the second half of 2020, with top-line data expected in
2021.
About AG10
AG10 is an investigational, orally-administered small molecule
designed to potently stabilize tetrameric transthyretin, or TTR,
thereby halting at its outset the series of molecular events that
give rise to TTR amyloidosis, or ATTR. In a randomized,
placebo-controlled Phase 2 clinical trial in patients with
symptomatic ATTR-CM, AG10 was generally well tolerated,
demonstrated greater than 90 percent average TTR stabilization at
Day 28, and increased serum TTR concentrations, a prognostic
indicator of survival in a retrospective study of ATTR-CM patients,
in a dose-dependent manner. The open label extension of this Phase
2 study identified no safety signals of potential clinical concern
associated with administration of AG10 15 months after study
initiation. In an exploratory analysis, lower rates of all-cause
mortality (including death and cardiac transplantation) and
cardiovascular hospitalizations were observed in study participants
than in placebo-treated ATTR-CM patients in the ATTR-ACT study.
Cardiac biomarkers and echocardiographic parameters were stable in
the AG10 Phase 2 OLE.
AG10 was designed to mimic a naturally-occurring variant of the
TTR gene (T119M) that is considered a rescue mutation because
co-inheritance has been shown to prevent or ameliorate ATTR in
individuals also inheriting a pathogenic, or disease-causing,
mutation in the TTR gene. To our knowledge, AG10 is the only TTR
stabilizer in development that has been observed to mimic the
stabilizing structure of this rescue mutation.
The Phase 3 ATTRibute-CM study of AG10 in patients with ATTR-CM
is underway. Part A of the study will assess the change from
baseline in 6-minute walk distance (6MWD) at 12 months. Part B of
the study will evaluate reduction in all-cause mortality and
frequency of cardiovascular-related hospitalizations at 30 months.
In addition, Eidos plans to initiate a Phase 3 study of AG10 in
ATTR polyneuropathy (ATTR-PN) in Q1 2020.
About transthyretin amyloidosis (ATTR)
There is significant medical need in transthyretin amyloidosis
(ATTR) given the large patient population and limited current
standard of care. ATTR is caused by the destabilization of TTR due
to inherited mutations or aging and is commonly divided into three
distinct categories: wild-type ATTR cardiomyopathy (ATTRwt-CM),
mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy
(ATTR-PN). The worldwide prevalence of each disease is estimated to
be at least 400,000 patients, 40,000 patients and 10,000 patients,
respectively.
All three forms of ATTR are progressive and fatal. For patients
with untreated ATTRwt-CM and ATTRm-CM, symptoms usually manifest
later in life (age 50+), with median survival of three to five
years from diagnosis. ATTR-PN either presents in a patient's early
30s or later (age 50+), and results in a median life expectancy of
five to ten years from diagnosis for untreated patients.
Progression of all forms of ATTR causes significant morbidity,
impacts productivity and quality of life, and creates a significant
economic burden due to the costs associated with progressively
greater patient needs for supportive care.
About BridgeBio Pharma
BridgeBio is a team of experienced drug discoverers, developers
and innovators working to create life-altering medicines that
target well-characterized genetic diseases at their source.
BridgeBio was founded in 2015 to identify and advance
transformative medicines to treat patients who suffer from
Mendelian diseases, which are diseases that arise from defects in a
single gene, and cancers with clear genetic drivers. BridgeBio’s
pipeline of over 15 development programs includes product
candidates ranging from early discovery to late-stage development.
For more information, please visit www.bridgebio.com.
About Eidos Therapeutics
Eidos is a BridgeBio Pharma subsidiary focused on addressing the
large and growing unmet need caused by transthyretin (TTR)
amyloidosis (ATTR). Eidos is developing AG10, a potentially
disease-modifying therapy for the treatment of ATTR. For more
information, please visit www.eidostx.com.
Forward-Looking Statements
This release includes forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933 and Section
21E of the Securities Exchange Act of 1934. All statements other
than statements of historical facts, including the statements about
the potential therapeutic and clinical benefits of AG10, the
potential for AG10 to be a best-in-class treatment for ATTR-CM
patients, the design of our ongoing Phase 3 ATTRibute-CM trial of
AG10, our ability to enroll patients in and conduct the
ATTRibute-CM trial and our planned Phase 3 clinical trial of AG10
in ATTR-PN in accordance with our plans, our ability to generate
data from and to complete these trials, the timing of these events,
the indications we intend to pursue and our possible clinical or
other business strategies, are forward-looking statements.
Forward-looking statements can be identified by terms such as
“believes,” “expects,” “plans,” “potential,” “would” or similar
expressions and the negative of those terms. These forward-looking
statements are based on our management’s current beliefs and
assumptions about future events and on information currently
available to management. Forward-looking statements involve
known and unknown risks, uncertainties and other factors that may
cause our actual results, performance or achievements to be
materially different from any future results, performance or
achievements expressed or implied by the forward-looking
statements. These risks include, but are not limited to, risks and
uncertainties related to: our limited operating history and
historical losses, our liquidity to fund the development of AG10
through current and future milestones, our ability to raise
additional funding to complete the development of AG10, our
dependence on the success of AG10, our ability to enroll patients
in the ATTRibute-CM trial and our planned Phase 3 clinical trial of
AG10 in ATTR-PN, results from our clinical trials
and pre-clinical studies and those of third parties
working in the same area as our product candidate, our ability to
advance AG10 in clinical development in accordance with our plans,
and our dependence on third parties in connection with our
manufacturing, clinical trials and pre-clinical studies.
Additional risks and uncertainties that could affect our future
results are included in the section titled “Risk Factors” and
“Management’s Discussion and Analysis of Financial Condition and
Results of Operations” in our Quarterly Report on Form 10-Q for the
quarter ended September 30, 2019, which is available on the SEC’s
website at www.sec.gov and our websites at eidostx.com
and bridgebio.com. Additional information on potential risks will
be made available in other filings that we make from time to time
with the SEC. In addition, any forward-looking statements contained
in this press release are based on assumptions that we believe to
be reasonable as of this date. Except as required by law, we assume
no obligation to update these forward-looking statements, or to
update the reasons if actual results differ materially from those
anticipated in the forward-looking statements.
Media Contact:Grace Rauh917-232-5478Grace.rauh@bridgebio.com
Investor Contact:John GrimaldiBurns
McClellan212-213-0006jgrimaldi@burnsmc.com
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