Vanda Pharmaceuticals Announces First Patient Dosed in a Trial Evaluating VCA-894A in Charcot-Marie-Tooth disease Type 2S

Rhea-AI Summary

Vanda Pharmaceuticals (VNDA) has initiated dosing in a first-in-human trial of VCA-894A, an antisense oligonucleotide therapeutic, targeting a rare variant of the IGHMBP2 gene that causes Charcot-Marie-Tooth disease Type 2S (CMT2S). The trial focuses on a patient diagnosed at age 5 with CMT2S, an inherited neuromuscular disorder affecting less than 1 in 1,000,000 people worldwide. VCA-894A has shown promising results in preclinical studies, successfully restoring IGHMBP2 gene expression levels in an organ-on-a-chip neuromuscular junction system derived from patient cells. This personalized therapeutic approach represents a potential breakthrough in treating rare genetic disorders, which collectively affect over 300 million people globally.

Positive

• Successful initiation of first-in-human trial for VCA-894A demonstrates progress in drug development pipeline
• Preclinical success in restoring gene expression levels in patient-derived cells shows therapeutic potential
• Company's platform technology could enable development of personalized treatments for other rare genetic disorders

Negative

• Extremely small target patient population (less than 1 in 1,000,000) may limit commercial potential
• Early-stage clinical trial with uncertain outcomes
• Personalized medicine approach may face scalability challenges

Insights

Biotechnology Research Physician

Vanda's first patient dosed with VCA-894A for ultra-rare CMT2S represents pioneering personalized genetic medicine but faces significant commercialization challenges.

Vanda has reached a clinical milestone with the dosing of the first patient in their VCA-894A trial, an antisense oligonucleotide (ASO) therapeutic designed for a patient with Charcot-Marie-Tooth disease Type 2S (CMT2S). This represents Vanda's expansion into personalized genetic medicine for ultra-rare conditions.

The scientific approach here is particularly noteworthy. The company developed VCA-894A to target a specific variant in the IGHMBP2 gene causing CMT2S in a single patient diagnosed at age 5. Preclinical validation using an "organ-on-a-chip" neuromuscular junction system derived from the patient's own cells demonstrated restoration of gene expression, suggesting potential efficacy.

CMT2S is an extraordinarily rare neuromuscular disorder with prevalence below 1 in 1,000,000 worldwide. The disease causes progressive muscle weakness and motor function loss. This represents both the promise and challenge of Vanda's approach - while scientifically impressive, the addressable patient population for this specific therapy appears to be just one patient.

The broader significance lies in Vanda's platform development for personalized ASO therapeutics targeting rare genetic disorders. If successful, this could establish a framework for treating other ultra-rare conditions with identified genetic variants. However, investors should recognize the substantial scientific, regulatory, and commercial challenges in developing individualized treatments for such small patient populations.

WASHINGTON, June 10, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced the first dose in the first-in-human clinical trial to evaluate the safety and tolerability of VCA-894A, an antisense oligonucleotide (ASO) therapeutic, for a patient with a rare variant in the IGHMBP2 gene causing Charcot-Marie-Tooth disease Type 2S (CMT2S).

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.¹ 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.² The severity and clinical presentations of CMT2S are influenced by the diverse genetic variants associated with CMT disease.

VCA-894A targets a patient-specific IGHMBP2 variant and has been previously shown to restore expression levels of the IGHMBP2 gene in an "organ-on-a-chip" NMJ (neuromuscular junction) system derived from the patient's cells, highlighting the exciting potential of this approach for personalized therapeutics for rare diseases. This platform has the potential to unlock the development of treatments that can address significantly unmet medical needs based on identified causative genetic variants.

Rare diseases collectively affect over 300 million people globally. Individualized treatments for such rare genetic disorders using nucleic acid-based platforms carry unprecedented potential to restore function where expression of crucial genes has been aberrant.

References:

1. Smieszek, S. et al. Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S. Mol Ther Nucleic Acids 36, 102479 (2025).
   
   
2. 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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SOURCE Vanda Pharmaceuticals Inc.

FAQ

What is the purpose of Vanda Pharmaceuticals' VCA-894A clinical trial?

The trial aims to evaluate the safety and tolerability of VCA-894A, an antisense oligonucleotide therapeutic, in treating a patient with Charcot-Marie-Tooth disease Type 2S caused by a rare IGHMBP2 gene variant.

What is CMT2S and how common is it?

CMT2S is an inherited neuromuscular disorder that causes progressive muscle weakness and loss of motor function, affecting less than 1 in 1,000,000 people worldwide.

What results has VNDA's VCA-894A shown in preclinical studies?

VCA-894A demonstrated success in restoring IGHMBP2 gene expression levels in an organ-on-a-chip neuromuscular junction system using the patient's cells.

How could this development impact Vanda Pharmaceuticals' future?

The platform technology could enable Vanda to develop personalized treatments for other rare genetic disorders, addressing a global market of over 300 million people affected by rare diseases.

What stage is VNDA's VCA-894A development currently in?

VCA-894A has just entered its first-in-human clinical trial phase, with the first patient being dosed in June 2025.