Vanda Pharmaceuticals announces the publication of an article titled "Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S"
Vanda Pharmaceuticals (VNDA) has published research on a novel antisense oligonucleotide (ASO) therapeutic, VCA-894A, developed for treating a patient with Charcot-Marie-Tooth disease Type 2S (CMT2S). The treatment targets a specific variant of the IGHMBP2 gene.
CMT2S is an inherited neuromuscular disorder causing progressive muscle weakness and motor function loss, with a prevalence of less than 1 in 1,000,000 worldwide. VCA-894A has shown significant improvements in neuromuscular function in testing, including reduced muscle fatigue and improved synaptic transmission between motor neurons and skeletal muscle myotubes.
The FDA has granted VCA-894A an orphan designation, and it is expected to be administered to the specific patient for whom it was developed. The experimental platform represents a breakthrough in precision medicine, potentially enabling the development of personalized treatments for rare genetic diseases.
Vanda Pharmaceuticals (VNDA) ha pubblicato una ricerca su un nuovo oligonucleotide antisenso (ASO) terapeutico, VCA-894A, sviluppato per trattare un paziente affetto da malattia di Charcot-Marie-Tooth di tipo 2S (CMT2S). Il trattamento mira a una specifica variante del gene IGHMBP2.
La CMT2S è un disturbo neuromuscolare ereditario che causa una progressiva debolezza muscolare e perdita della funzione motoria, con una prevalenza di meno di 1 su 1.000.000 a livello mondiale. VCA-894A ha mostrato significativi miglioramenti nella funzione neuromuscolare nei test, inclusa la riduzione della fatica muscolare e il miglioramento della trasmissione sinaptica tra i neuroni motori e i miotubi muscolari scheletrici.
La FDA ha concesso a VCA-894A una designazione di farmaco orfano, e si prevede che venga somministrato al paziente specifico per il quale è stato sviluppato. La piattaforma sperimentale rappresenta una svolta nella medicina di precisione, potenzialmente abilitando lo sviluppo di trattamenti personalizzati per malattie genetiche rare.
Vanda Pharmaceuticals (VNDA) ha publicado una investigación sobre un nuevo oligonucleótido antisentido (ASO) terapéutico, VCA-894A, desarrollado para tratar a un paciente con la enfermedad de Charcot-Marie-Tooth tipo 2S (CMT2S). El tratamiento se dirige a una variante específica del gen IGHMBP2.
La CMT2S es un trastorno neuromuscular hereditario que causa debilidad muscular progresiva y pérdida de función motora, con una prevalencia de menos de 1 en 1.000.000 a nivel mundial. VCA-894A ha mostrado mejoras significativas en la función neuromuscular en las pruebas, incluyendo la reducción de la fatiga muscular y la mejora de la transmisión sináptica entre las neuronas motoras y los miotubos musculares esqueléticos.
La FDA ha otorgado a VCA-894A una designación de medicamento huérfano, y se espera que se administre al paciente específico para el que fue desarrollado. La plataforma experimental representa un avance en la medicina de precisión, permitiendo potencialmente el desarrollo de tratamientos personalizados para enfermedades genéticas raras.
반다 제약 (VNDA)는 샤르코-마리-투스병 2S형 (CMT2S) 환자를 치료하기 위해 개발된 새로운 항센스 올리고뉴클레오타이드 (ASO) 치료제인 VCA-894A에 대한 연구를 발표했습니다. 이 치료는 IGHMBP2 유전자의 특정 변이를 목표로 합니다.
CMT2S는 유전성 신경근육 질환으로, 점진적인 근육 약화와 운동 기능 상실을 초래하며, 전 세계적으로 100만 명당 1명 미만의 유병률을 보입니다. VCA-894A는 테스트에서 신경근육 기능의 상당한 개선을 보여주었으며, 여기에는 근육 피로 감소와 운동 뉴런과 골격근 미오튜브 간의 시냅스 전송 개선이 포함됩니다.
FDA는 VCA-894A에 고아약 지정을 부여했으며, 이는 개발된 특정 환자에게 투여될 것으로 예상됩니다. 이 실험적 플랫폼은 정밀 의학의 혁신을 나타내며, 희귀 유전 질환에 대한 개인 맞춤형 치료 개발을 가능하게 할 수 있습니다.
Vanda Pharmaceuticals (VNDA) a publié des recherches sur un nouvel oligonucleotide antisens (ASO) thérapeutique, VCA-894A, développé pour traiter un patient atteint de la maladie de Charcot-Marie-Tooth de type 2S (CMT2S). Le traitement cible une variante spécifique du gène IGHMBP2.
La CMT2S est un trouble neuromusculaire héréditaire provoquant une faiblesse musculaire progressive et une perte de fonction motrice, avec une prévalence de moins de 1 sur 1.000.000 dans le monde. VCA-894A a montré des améliorations significatives de la fonction neuromusculaire lors des tests, y compris une réduction de la fatigue musculaire et une amélioration de la transmission synaptique entre les neurones moteurs et les myotubes musculaires squelettiques.
La FDA a accordé à VCA-894A une désignation de médicament orphelin, et il est prévu qu'il soit administré au patient spécifique pour lequel il a été développé. La plateforme expérimentale représente une avancée dans la médecine de précision, permettant potentiellement le développement de traitements personnalisés pour les maladies génétiques rares.
Vanda Pharmaceuticals (VNDA) hat eine Forschung zu einem neuartigen Antisense-Oligonukleotid (ASO) Therapeutikum, VCA-894A, veröffentlicht, das zur Behandlung eines Patienten mit Charcot-Marie-Tooth-Krankheit Typ 2S (CMT2S) entwickelt wurde. Die Behandlung zielt auf eine spezifische Variante des IGHMBP2-Gens ab.
CMT2S ist eine erbliche neuromuskuläre Erkrankung, die zu fortschreitender Muskelschwäche und Verlust der motorischen Funktion führt, mit einer Prävalenz von weniger als 1 von 1.000.000 weltweit. VCA-894A hat in Tests signifikante Verbesserungen der neuromuskulären Funktion gezeigt, einschließlich verringerter Muskelermüdung und verbesserter synaptischer Übertragung zwischen motorischen Neuronen und Skelettmuskel-Miotuben.
Die FDA hat VCA-894A eine Orphan-Designation erteilt, und es wird erwartet, dass es dem spezifischen Patienten verabreicht wird, für den es entwickelt wurde. Die experimentelle Plattform stellt einen Durchbruch in der Präzisionsmedizin dar und könnte die Entwicklung personalisierter Behandlungen für seltene genetische Erkrankungen ermöglichen.
- FDA granted orphan designation for VCA-894A
- Successful demonstration of treatment efficacy in laboratory testing
- Development of novel personalized treatment platform for rare genetic diseases
- Extremely market potential (less than 1 in 1,000,000 prevalence)
- Treatment is specific to single patient, limiting commercial scalability
Insights
This breakthrough in personalized medicine represents a pivotal moment for Vanda Pharmaceuticals, demonstrating their capability to develop ultra-rare disease treatments. The successful development of VCA-894A showcases three critical advantages:
First, the company's technological platform for developing personalized ASO therapeutics could be applied to numerous rare genetic conditions, potentially opening up a new market segment. While CMT2S affects less than 1 in 1,000,000 people worldwide, the collective rare disease market is substantial, with approximately 400 million people globally affected by rare diseases.
The FDA's orphan designation for VCA-894A is particularly significant as it provides several benefits, including tax credits for clinical trials, exemption from user fees, and seven years of market exclusivity upon approval. This regulatory pathway could serve as a template for future personalized treatments.
The use of Hesperos' Human-on-a-Chip® technology for validation is noteworthy, as it potentially reduces development time and costs while improving predictive accuracy. This could accelerate the development pipeline for similar personalized treatments and improve success rates in clinical applications.
However, investors should consider several key factors: The ultra-personalized nature of the treatment presents unique challenges in pricing and reimbursement models. The scalability of this approach and its economic viability will depend on Vanda's ability to streamline development processes and establish efficient manufacturing protocols for individual patient treatments.
The platform's potential extends beyond CMT2S - it could be adapted for other genetic conditions where similar mechanisms are involved. This versatility could position Vanda as a pioneer in personalized genetic medicines, potentially leading to multiple treatment programs and expanded market opportunities.
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
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.
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