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 that AT-007 (govorestat)
has been granted orphan medicinal product designation by the
European Medicines Agency (EMA) for treatment of Sorbitol
Dehydrogenase (SORD) Deficiency. Additionally, the Company
announced that new data has been published in the Journal of
Clinical Investigation on govorestat treatment in models of SORD
Deficiency.
EMA Orphan Medicinal Product Designation of AT-007
(govorestat) in SORD Deficiency
“We are pleased that the EMA has recognized the high unmet
medical need in SORD Deficiency, and the benefit of govorestat
treatment in reducing toxic sorbitol levels in patients with SORD
Deficiency as well as preventing disease progression in the animal
model of disease,” said Shoshana Shendelman, PhD, Founder and CEO
of Applied Therapeutics. “Orphan designation for govorestat marks
an important step towards advancing our regulatory initiatives in
Europe.”
Orphan medicinal product designation provides certain benefits
and incentives in the EU, including protocol assistance, fee
reductions, and ten years of market exclusivity once the medicine
is on the market. Applied Therapeutics has partnered govorestat for
treatment of SORD Deficiency as well as Galactosemia in Europe with
ADVANZ Pharma.
Sorbitol reduction via govorestat ameliorates synaptic
dysfunction and neurodegeneration in sorbitol dehydrogenase
deficiency Yi Zhu, Amanda G. Lobato, Adriana P. Rebelo,
Tijana Canic, Natalie Ortiz-Vega, Xianzun Tao,Sheyum Syed,
Christopher Yanick, Mario Saporta, Michael Shy, Riccardo Perfetti,
ShoshanaShendelman, Stephan Züchner, R. Grace ZhaiJournal of
Clinical Investigation: May 22, 2023 Volume 8 Issue 10
The new data on govorestat treatment in models of SORD
Deficiency was recently published in the Journal of Clinical
Investigation. The article can be accessed here.
https://insight.jci.org/articles/view/164954/pdf
The molecular and cellular pathophysiology of SORD neuropathy
was investigated through use of patient-derived cells and a
drosophila model of disease, finding reduced adenosine triphosphate
(ATP) production and reactive oxygen species (ROS) accumulation in
the central nervous system (CNS) and muscle, indicating
mitochondrial dysfunction as a result of increased sorbitol
accumulation. Govorestat treatment significantly reduced sorbitol
levels in patient-derived fibroblasts, patient iPSC-derived motor
neurons, and SORD-deficient drosophila. Govorestat treatment in the
SORD drosophila model mitigated synaptic degeneration and
significantly improved synaptic transduction, locomotor activity,
and mitochondrial function. Moreover, govorestat treatment
significantly reduced ROS accumulation in patient derived cells and
drosophila CNS and muscle. These findings uncover the molecular and
cellular pathophysiology of sorbitol toxicity in SORD neuropathy,
and govorestat provides a potential treatment strategy for patients
with SORD Deficiency.
About Sorbitol Dehydrogenase (SORD)
Deficiency
Sorbitol Dehydrogenase Deficiency (SORD Deficiency) is a rare,
progressive, debilitating hereditary neuropathy that affects
peripheral nerves and motor neurons. SORD Deficiency is one of the
most common forms of recessive hereditary neuropathy and affects
approximately 3,300 patients in the U.S. and 4,000 patients in
Europe. The disease is caused by a lack of the enzyme sorbitol
dehydrogenase, responsible for the metabolism of sorbitol, which
causes sorbitol to accumulate at high levels and become toxic to
the body. Intracellular sorbitol accumulation results in
significant disability, loss of sensory function, neuromuscular
dysfunction, and decreased mobility.
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 AT-007 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, AT-007 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 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 strategy, future
operations, prospects, plans and objectives of management,
including words such as “may,” “will,” “expect,” “anticipate,”
“plan,” “intend,” and similar expressions (as well as other words
or expressions referencing future events, conditions or
circumstances) are forward-looking statements. 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,
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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