WASHINGTON, Feb. 24,
2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc.
(Vanda) (Nasdaq: VNDA) today announced the publication of an
article entitled "Potential ASO-based personalized treatment for
Charcot-Marie-Tooth disease type 2S" in Molecular Therapy Nucleic
Acids1, a Cell Press partner journal, that describes the
development of a novel antisense oligonucleotide (ASO) therapeutic,
VCA-894A, for a patient with a rare variant in the IGHMBP2
gene causing Charcot-Marie-Tooth disease Type 2S (CMT2S).
In 1886, Jean-Martin Charcot, Pierre
Marie, and Henry Tooth
independently described this hereditary motor and sensory
neuropathy in their patients, paving the way for
Charcot-Marie-Tooth (CMT) disease research.2,3 It was
not until 1968 that a distinction was made in CMT disease, creating
the classification of CMT1 and CMT2.4 Since then, CMT
disease (OMIM: 616155) has been used as a model disease to
describe genetic heterogeneity.5 However, the high
genetic and allelic heterogeneity of CMT disease poses a challenge
for both diagnosis and treatment.
VCA-894A is being developed for a patient who was first
diagnosed at the age of 5 with a rare subtype of CMT disease known
as CMT2S.6 CMT2S is an inherited neuromuscular
disorder that progressively leads to muscle weakness and loss of
motor function, and has an estimated prevalence of less than 1 in
1,000,000 worldwide.7 The severity and clinical
presentations of CMT2S are influenced by the diverse genetic
variants associated with CMT disease, emphasizing the importance of
principal and modifying genes in human diseases. VCA-894A targets a
patient-specific IGHMBP2 variant and restores expression
levels of IGHMBP2, highlighting the exciting potential of this
approach for personalized therapeutics for rare diseases.
"More than two decades after the human genome was first
sequenced, we are now able to perform routine and affordable
sequencing of the genome for any individual, enabling the discovery
of genetic causes of disease and facilitating the development of
targeted therapeutics. Our efforts to develop an antisense
oligonucleotide treatment for a patient with a specific genetic
mutation causing the neuromuscular disorder CMT2S is a
demonstration of how these novel technologies can be leveraged to
develop a new treatment paradigm – moving away from the
one-treatment-fits-all perspective and towards the development of
personalized medicines," said Mihael H. Polymeropoulos,
M.D., Vanda's President, CEO and Chairman of the Board.
The article1 published today discusses the
development of this novel breakthrough therapeutic customized to a
specific genetic mutation of a patient with CMT2S. The effects of
VCA-894A were confirmed in Hesperos' Human-on-a-Chip®
neuromuscular junction model with patient-derived cells where
VCA-894A demonstrated significant improvements in neuromuscular
function, including reduced muscle fatigue and improved synaptic
transmission between motor neurons and skeletal muscle myotubes.
The use of a microphysiological system to evaluate the effects of a
genetically tailored treatment represents a significant advancement
in precision medicine and the use of human relevant methods of
evaluation.
VCA-894A has been granted an orphan designation by the FDA and
it is expected to soon be administered to the specific patient for
whom it was developed. The experimental platform described in
today's article has the potential to unlock the development of
treatments that can address significantly unmet medical needs based
on genetic understandings and precision medicine.
For access to the full study, visit
DOI: 10.1016/j.omtn.2025.102479.
References:
- Smieszek, S. et al. Potential ASO-based personalized
treatment for Charcot-Marie-Tooth disease type 2S. Mol Ther
Nucleic Acids 36, 102479 (2025).
- Charcot, J. M. & Marie, P. Sur Une Forme Particulière
d'atrophie Musculaire Progressive : Souvent Familiale Débutant Par
Les Pieds et Les Jambes et Atteignant plus Tard Les Mains. vol.
6 (Revue de médecine, 1886).
- Tooth, H. H. The Peroneal Type of Progressive Muscular
Atrophy. Dissertation, University of
Cambridge. (1886).
- Dyck, P. J. Lower Motor and Primary Sensory Neuron Diseases
With Peroneal Muscular Atrophy. Arch Neurol 18, 603
(1968).
- Lupski, J. R. et al. Whole-Genome Sequencing in a Patient
with Charcot–Marie–Tooth Neuropathy. New England Journal of
Medicine 362, 1181–1191 (2010).
- Cassini, T. A. et al. Whole genome sequencing reveals novel
IGHMBP2 variant leading to unique cryptic splice-site and
Charcot-Marie-Tooth phenotype with early onset symptoms. Mol
Genet Genomic Med 7, (2019).
- Charcot-Marie-Tooth disease type 2S. Orpha.net (2025).
https://www.orpha.net/en/disease/detail/443073
About Vanda Pharmaceuticals Inc.
Vanda is a leading global biopharmaceutical company focused on
the development and commercialization of innovative therapies to
address high unmet medical needs and improve the lives of patients.
For more on Vanda Pharmaceuticals Inc., please visit
www.vandapharma.com and follow us on X @vandapharma.
About VCA-894A
VCA-894A is a 2'-O-methoxyethyl (MOE) phosphorothioate
oligonucleotide sodium salt. VCA-894A specifically targets a
cryptic splice site variant within IGHMBP2, which causes CMT2S.
ASOs may have broad applicability in addressing a number of
disorders, from nervous system treatments to systemic
treatments.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Various statements in this press release, including, but not
limited to statements regarding the estimated prevalence of CMT2S,
the development of individualized treatments and the timing of the
expected administration of VCA-894A to patient for whom it was
developed, are "forward-looking statements" under the securities
laws. All statements other than statements of historical fact are
statements that could be deemed forward-looking statements.
Forward-looking statements are based upon current expectations and
assumptions that involve risks, changes in circumstances and
uncertainties. Important factors that could cause actual results to
differ materially from those reflected in Vanda's forward-looking
statements include, among others, the accuracy of the reporting and
diagnosis of CMT2S cases, the ability of Vanda's experimental
platform to allow for the development of precision medicines that
address significant unmet medical needs and Vanda's ability to
administer VCA-894A to the patient for whom it was developed in the
expected timeframe. Therefore, no assurance can be given that the
results or developments anticipated by Vanda will be realized or,
even if substantially realized, that they will have the expected
consequences to, or effects on, Vanda. Forward-looking statements
in this press release should be evaluated together with the various
risks and uncertainties that affect Vanda's business and market,
particularly those identified in the "Cautionary Note Regarding
Forward-Looking Statements", "Risk Factors" and "Management's
Discussion and Analysis of Financial Condition and Results of
Operations" sections of Vanda's most recent Annual Report on Form
10-K, as updated by Vanda's subsequent Quarterly Reports on Form
10-Q, Current Reports on Form 8-K and other filings with the U.S.
Securities and Exchange Commission, which are available at
www.sec.gov.
All written and verbal forward-looking statements attributable
to Vanda or any person acting on its behalf are expressly qualified
in their entirety by the cautionary statements contained or
referred to herein. Vanda cautions investors not to rely too
heavily on the forward-looking statements Vanda makes or that are
made on its behalf. The information in this press release is
provided only as of the date of this press release, and Vanda
undertakes no obligation, and specifically declines any obligation,
to update or revise publicly any forward-looking statements,
whether as a result of new information, future events or otherwise,
except as required by law.
Corporate Contact:
Kevin
Moran
Senior Vice President, Chief Financial Officer and Treasurer
Vanda Pharmaceuticals Inc.
202-734-3400
pr@vandapharma.com
Jim Golden / Jack Kelleher / Dan
Moore
Collected Strategies
VANDA-CS@collectedstrategies.com
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