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 results from the
ACTION-Galactosemia Kids study of govorestat (AT-007), a novel,
oral, small molecule, central nervous system (CNS) penetrant Aldose
Reductase inhibitor (ARI).
“We believe Govorestat has demonstrated
compelling evidence of clinical benefit alongside a favorable
safety profile in patients with Galactosemia,” said Shoshana
Shendelman, PhD, CEO, Founder and Chair of the Board of Applied
Therapeutics. “We look forward to working collaboratively with
regulators to ensure that this important treatment is available to
patients with Galactosemia as quickly as possible. We plan to
request a pre-NDA meeting with the FDA, and we have already
received feedback from the EMA supportive of a submission in
Europe.”
“Govorestat has demonstrated consistent results
on improvement in galactitol biomarker levels in both adults and
children and on long-term clinical and functional outcomes in
children with Galactosemia,” said Riccardo Perfetti, MD, PhD, Chief
Medical Officer of Applied Therapeutics. “We would like to thank
all of the patients, investigators, and caregivers who participated
in the ACTION-Galactosemia Kids study.”
“In the ACTION-Galactosemia Kids trial,
treatment with govorestat affected clinically meaningful
aspects of the disease, including activities of daily living,
behavioral symptoms, cognition, adaptive skills and tremor,” said
Janet Thomas, MD, Director of Clinical Research, Section of
Clinical Genetics and Metabolism, Children’s Hospital Colorado.
“This is exciting news. Until now, physicians
have had no pharmacological options available for
Galactosemia, and I look forward to being able to provide this
therapy to my patients in the future.”
“The Galactosemia community has been waiting for
a treatment for a long time, and we are thrilled with the results
from the ACTION-Galactosemia Kids trial. Govorestat clearly
improves critical characteristics of this disease - like our
children’s abilities to feed themselves, dress themselves,
understand what they are being taught in school, interact with
other children - all of which impact our daily lives.” said
Brittany Cudzilo, Vice President of the Galactosemia
Foundation.
The ACTION-Galactosemia Kids Phase 3 study was
designed to evaluate the impact of govorestat treatment vs. placebo
on clinical outcomes over time in 47 children age 2-17 with
Galactosemia. The primary endpoint, the Global Statistical Test,
was a composite sum of change comprised of four endpoints: OWLS-2
Oral Expression (OE), OWLS-2 Listening Comprehension (LC), BASC-3
Behavior Symptoms Index (BSI) and the BASC-3 Activities of Daily
Living (ADL). An additional pre-specified sensitivity analysis
included cognition in the primary endpoint (NIH-Toolbox Cognition
Battery). Additional clinical outcomes were assessed as secondary
endpoints, including adaptive skills and tremor. Clinical outcomes
were assessed every 6 months by a firewalled independent Data
Monitoring Committee (DMC).
- Treatment with govorestat demonstrated consistent and sustained
clinical benefit on activities of daily living, behavioral
symptoms, cognition, adaptive behavior and tremor.
- While statistical significance defined as a p value of <0.05
was not met on the primary endpoint, systematic improvement over
time was demonstrated for the overall primary endpoint (p=0.1030)
and for a pre-specified sensitivity analyses including cognition
(p=0.0698).
- Individual speech and language components of the primary
endpoint were not impacted, which is suspected to be due to lack of
progression in the placebo group and concomitant speech therapy
received by almost all children in the trial. Of note, patients
with severe speech deficits showed a favorable trend towards
improvement with govorestat vs. placebo.
- A post-hoc analysis of the global statistical test including
behavior and activities of daily living but excluding speech &
language components (OWLS-OE and OWLS-LC) demonstrated a highly
statistically significant benefit of active treatment vs. placebo
(p=0.0205), which strengthened over time.
- Govorestat provided a statistically significant benefit on
tremor at 18 months (p=0.0428), as measured by the Archimedes
Spiral Drawing Test, and adaptive skills as assessed by the BASC-3
Adaptive Skills Index (p=0.0265).
- Consistent with prior reported data, improvement in galactitol
levels was sustained throughout the trial with no impact on Gal-1p
or galactose, further establishing the causal role of galactitol in
disease pathogenesis.
- Govorestat continued to be safe and well-tolerated in all age
groups; there were no treatment-related serious adverse events
(SAEs) reported.
This data will be submitted for presentation at
an upcoming medical conference.
The Company believes that there is compelling
evidence of clinical efficacy and plans to move toward registration
of govorestat for Galactosemia. The trial will be unblinded and
placebo patients will be crossed to active treatment.
The Company will host a conference call to
discuss the results today at 8:30am Eastern.
To access the conference call, please dial (833)
630-1956 (local) or (412) 317-1837 (international) at least 10
minutes prior to the start time and ask to be joined into the
Applied Therapeutics call. A live webcast of the call will be
accessible on the Events page under the Investor Relations section
of the Applied Therapeutics website at www.appliedtherapeutics.com.
A replay will be available on the Company’s website approximately
two hours after the event.
About GalactosemiaGalactosemia
is a rare genetic metabolic disease resulting in an inability to
metabolize the simple sugar galactose. Galactose is found in foods,
but is also produced endogenously by the body. When not metabolized
properly, galactose is converted to the toxic metabolite,
galactitol, which causes neurological complications, including
deficiencies in speech, cognition, behavior, and motor skills, and
also results in juvenile cataracts and ovarian insufficiency (in
women). There are approximately 3,000 patients with Galactosemia in
the US and 80 new births per year, and approximately 4,000 patients
with Galactosemia in the EU and 120 new births per year.
About Govorestat
(AT-007)Govorestat is a central nervous system (CNS)
penetrant Aldose Reductase inhibitor (ARI) in development for the
treatment of several rare neurological diseases, including
Galactosemia, SORD Deficiency, and PMM2-CDG.
In a study in children with Galactosemia aged
2-17, treatment with govorestat demonstrated clinical benefit on
activities of daily living, behavioral symptoms, cognition, fine
motor skills and tremor. Govorestat also significantly reduced
plasma galactitol levels in both adults and children with
Galactosemia. Galactitol is a toxic metabolite responsible for
tissue damage and long-term complications in Galactosemia.
Govorestat is also being studied in the ongoing
Phase 3 INSPIRE trial, which is evaluating the effect of AT-007 vs.
placebo in patients with SORD Deficiency on sorbitol reduction as
well as clinical outcomes in approximately 50 patients aged 16-55
in the US and Europe. In an interim analysis, govorestat reduced
sorbitol by a mean of 52%, or approximately 16,000 ng/ml, over a
90-day period, which was highly statistically significant vs.
placebo (p<0.001).
Govorestat has received Orphan Medicinal Product
Designation from the European Medicines Agency (EMA) for both
Galactosemia and SORD Deficiency. Govorestat has also received
Orphan Drug Designation from the U.S. Food and Drug Administration
(FDA) for the treatment of Galactosemia, PMM2-CDG, and SORD
Deficiency; Pediatric Rare Disease designation for Galactosemia and
PMM2-CDG; and Fast Track designation for Galactosemia.
About Applied
TherapeuticsApplied 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 StatementsThis
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 (i) the Company’s plans to request a pre-NDA
meeting with the FDA to discuss a potential NDA submission in the
second half of 2023; plans to submit a Marketing Authorization
Application (MAA) with the European Medicines Agency (EMA) in
mid-2023 and (ii) the Company’s belief with respect to the clinical
benefits of govorestat. 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, (xvii) 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 appliedtherapeutics@argotpartners.com
Media:media@appliedtherapeutics.com
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