Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage
biopharmaceutical company developing a pipeline of novel drug
candidates against validated molecular targets in indications of
high unmet medical need, today announced the topline results of the
ARISE-HF Phase 3 trial of AT-001 (caficrestat) in patients with
Diabetic Cardiomyopathy (DbCM) at high risk of progression to overt
heart failure.
The primary endpoint
of the study was stabilization or improvement in cardiac functional
capacity as measured by Peak VO2 in patients treated with AT-001
1500mg twice daily (BID) as compared to placebo. The
placebo-treated group declined by a mean of -0.31 ml/kg/min over 15
months of treatment, while the AT-001 1500mg BID group remained
primarily stable, with a mean change of -0.01 ml/kg/min over 15
months. While a trend favored active treatment, the difference
between active and placebo treated groups (0.30 ml/kg/min) was not
statistically significant (p=0.210).
The ARISE-HF study
evaluated the treatment effect of AT-001 as an add-on to diabetes
standard of care therapies. Approximately 38% of study subjects
were on SGLT2 or GLP-1 therapies for treatment of diabetes, while
62% were not. In a pre-specified subgroup analysis of the primary
endpoint in patients not concomitantly treated with SGLT2 or GLP-1
therapies, the placebo group declined by a mean of -0.54 ml/kg/min,
while the 1500mg BID AT-001 treated group improved by a mean of
0.08 ml/kg/min over 15 months of treatment, with a difference
between groups of 0.62 ml/kg/min (p=0.040). Additionally, in this
subgroup analysis, the number of patients who experienced a
clinically significant worsening in cardiac functional capacity of
6% or more was substantially higher in the placebo group (46%) as
compared to the 1500mg BID AT-001 treated group (32.7%), odds ratio
0.56 (p=0.035). A 6% change in cardiac functional capacity has been
shown to predict long-term survival and hospitalization for heart
failure. The effect of AT-001 was dose dependent, with the low dose
(1000mg BID) demonstrating an intermediate effect between the high
dose and placebo.
AT-001 was generally
safe and well tolerated, with no substantial differences in serious
adverse events between AT-001 treated groups as compared to placebo
(14.3% placebo; 12.3% AT-001 1000mg BID; 17.3% AT-001 1500mg BID),
no substantial differences in treatment emergent adverse events
(79.1% placebo; 81.6% AT-001 1000mg BID; 81% AT-001 1500mg BID) and
low incidence of treatment-related discontinuations (3.9% placebo;
9.6% AT-001 1000mg BID; 9.5% AT-001 1500mg BID).
Full study results
will be presented at an upcoming medical conference, along with
results of the Diabetic Peripheral Neuropathy sub-study, which are
still being analyzed.
“AT-001 stabilized cardiac functional capacity
as compared to placebo, and prevented clinically significant
worsening of disease, an effect which was strengthened in patients
not on concomitant treatment with an SGLT2 or GLP-1,” said Riccardo
Perfetti, MD, PhD, Chief Medical Officer of Applied Therapeutics.
“Given its favorable safety and tolerability profile and oral
dosing, we believe that AT-001 represents an important potential
tool for physicians in treatment of DbCM patients. We thank the
patients and families who participated in the ARISE-HF study and
made this important work possible.”
“There are currently no therapies approved for
DbCM, and a high unmet need exists for a treatment that can prevent
worsening of the condition and progression to overt heart failure,”
said James Januzzi, M.D., Principal investigator of the ARISE-HF
study and Hutton Family Professor of Cardiology at Massachusetts
General Hospital. “Stabilization of cardiac functional capacity is
an exciting finding, since declining functional capacity is a
leading indicator of progression to overt heart
failure.”
Given these
encouraging results, the Company plans to focus on identifying an
appropriate path forward through partnering in order to bring
AT-001 to DbCM patients. Current resources are expected to be
focused on the development, regulatory and commercial preparations
for the govorestat rare disease program. The Company submitted a
New Drug Application (NDA) to the U.S. Food and Drug Administration
(FDA) in December 2023 for govorestat for the treatment of Classic
Galactosemia. The Marketing Authorization Application (MAA) was
validated and accepted for review by the European Medicines Agency
(EMA) in December 2023.
About AT-001
(Caficrestat)
AT-001 (caficrestat) is an
investigational oral, novel, potent Aldose Reductase inhibitor in
Phase 3 clinical development for the treatment of Diabetic
Cardiomyopathy. The global ARISE-HF Phase 3 study evaluated the
ability of AT-001 to improve or prevent worsening of disease, as
measured by changes in cardiac functional capacity, in 675 patients
with DbCM at high risk of progression to overt heart failure. The
study demonstrated a positive impact of AT-001 treatment, which was
statistically significant in a prespecified subgroup of patients
not on concomitant treatment with an SGLT2 or GLP-1 inhibitor.
AT-001 has been previously studied in a Phase 1/2 study in
approximately 120 patients with type 2 diabetes, a subset of which
had DbCM.
About Applied
Therapeutics
Applied Therapeutics is a
clinical-stage biopharmaceutical company developing a pipeline of
novel drug candidates against validated molecular targets in
indications of high unmet medical need. The Company’s lead drug
candidate, govorestat, is a novel central nervous system penetrant
Aldose Reductase Inhibitor (ARI) for the treatment of CNS rare
metabolic diseases, including Galactosemia, SORD Deficiency, and
PMM2-CDG. The Company is also developing AT-001, a novel potent
ARI, for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal
fibrosis of the heart. The preclinical pipeline also includes
AT-003, an ARI designed to cross through the back of the eye when
dosed orally, for the treatment of Diabetic retinopathy.
To learn more, please
visit www.appliedtherapeutics.com and follow the company on Twitter
@Applied_Tx.
Forward-Looking
Statements
This press release contains
“forward-looking statements” that involve substantial risks and
uncertainties for purposes of the safe harbor provided by the
Private Securities Litigation Reform Act of 1995. Any statements,
other than statements of historical fact, included in this press
release regarding the strategy, future operations, prospects, plans
and objectives of management, including words such as “may,”
“will,” “expect,” “anticipate,” “plan,” “intend,” “predicts” and
similar expressions (as well as other words or expressions
referencing future events, conditions or circumstances) are
forward-looking statements. These include, without limitation,
statements regarding the Company’s (i) plan to focus on identifying
an appropriate path forward through partnering in order to bring
AT-001 to DbCM patients and (ii) expectation for current resources
to be focused on the development, regulatory and commercial
preparations for the govorestat rare disease program.
Forward-looking statements in this release involve substantial
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by the forward-looking
statements, and we, therefore cannot assure you that our plans,
intentions, expectations or strategies will be attained or
achieved.
Such risks and uncertainties include,
without limitation, (i) our plans to develop, market and
commercialize our product candidates, (ii) the initiation, timing,
progress and results of our current and future preclinical studies
and clinical trials and our research and development programs,
(iii) our ability to take advantage of expedited regulatory
pathways for any of our product candidates, (iv) our estimates
regarding expenses, future revenue, capital requirements and needs
for additional financing, (v) our ability to successfully acquire
or license additional product candidates on reasonable terms and
advance product candidates into, and successfully complete,
clinical studies, (vi) our ability to maintain and establish
collaborations or obtain additional funding, (vii) our ability to
obtain and timing of regulatory approval of our current and future
product candidates, (viii) the anticipated indications for our
product candidates, if approved, (ix) our expectations regarding
the potential market size and the rate and degree of market
acceptance of such product candidates, (x) our ability to fund our
working capital requirements and expectations regarding the
sufficiency of our capital resources, (xi) the implementation of
our business model and strategic plans for our business and product
candidates, (xii) our intellectual property position and the
duration of our patent rights, (xiii) developments or disputes
concerning our intellectual property or other proprietary rights,
(xiv) our expectations regarding government and third-party payor
coverage and reimbursement, (xv) our ability to compete in the
markets we serve, (xvi) the impact of government laws and
regulations and liabilities thereunder, (xvii) developments
relating to our competitors and our industry, (xviii) our ability
to achieve the anticipated benefits from the agreements entered
into in connection with our partnership with Advanz Pharma and
(xiv) other factors that may impact our financial results. In light
of the significant uncertainties in these forward-looking
statements, you should not rely upon forward-looking statements as
predictions of future events. Although we believe that we have a
reasonable basis for each forward-looking statement contained in
this press release, we cannot guarantee that the future results,
levels of activity, performance or events and circumstances
reflected in the forward-looking statements will be achieved or
occur at all. Factors that may cause actual results to differ from
those expressed or implied in the forward-looking statements in
this press release are discussed in our filings with the U.S.
Securities and Exchange Commission, including the “Risk Factors”
contained therein. Except as otherwise required by law, we disclaim
any intention or obligation to update or revise any forward-looking
statements, which speak only as of the date they were made, whether
as a result of new information, future events or circumstances or
otherwise.
Contacts
Investors:Maeve
Conneighton (212) 600-1902
orappliedtherapeutics@argotpartners.com
Media:media@appliedtherapeutics.com
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