FDA awards special status to custom CMT treatment for ultrarare subtype

A novel treatment being developed by Vanda Pharmaceuticals for a single patient with Charcot-Marie-Tooth disease type 2S (CMT2S) — an ultrarare type of this genetic disorder — has been granted rare pediatric disease designation by the U.S. Food and Drug Administration (FDA).

That regulatory status aims to incentivize the development of therapies for serious or life-threatening rare diseases that primarily affect children. If the treatment is ultimately approved, the company may become eligible for a priority review voucher, which could shorten the time the FDA would take to review a separate application for another treatment.

Called VCA-894A, this therapy has thus far been tested in one patient in a clinical trial in Madison, Wisconsin. Vanda stated in a company press release that the treatment’s therapeutic target “is a unique variant of CMT2S not yet observed in any other patient.”

According to Mihael H. Polymeropoulos, MD, Vanda’s president, chairman, and CEO, “the FDA’s Rare Pediatric Disease Designation recognizes the significant unmet medical need in this patient population and supports our efforts to develop a potentially transformative therapy for patients affected by this rare disease.”

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Charcot-Marie-Tooth disease (CMT) is a group of genetic neurological disorders that affect the peripheral nervous system — the network of nerves that control movement and sensations in the arms and legs. In CMT type 2, the disease disrupts the structure and function of axons, which are nerve cell projections that transmit signals to other nerve cells or muscles.

This specific subtype is caused by mutations in both copies of the IGHMBP2 gene, which provides instructions for producing an enzyme needed for protein production and cell division. The disease typically manifests in early childhood, causing progressive muscle weakness and wasting, as well as sensory loss in the arms and legs.

“CMT2S is a devastating inherited neuropathy for which patients and families have limited treatment options,” Polymeropoulos said.

CMT treatment tested in trial involved single participant

VCA-894A is an antisense oligonucleotide, a small, lab-made strand of genetic material designed to target a splice site variant. This type of mutation alters the protein-coding sequence and leads to abnormal processing of RNA, the molecule generated from DNA that serves as a template for protein production.

In the Phase 1/2 clinical trial (NCT07223632) launched last year, Vanda dosed a single participant. According to the company, the therapy “is being developed for a patient who was first diagnosed at an early age with [this] rare subtype.”

The trial was designed to evaluate safety, tolerability, and motor function as primary outcome measures.

The treatment was previously shown to restore IGHMBP2 gene activity in a so-called organ-on-a-chip model of the neuromuscular junction — the site where nerve and muscle cells communicate — derived from patients’ cells, according to the company.

VCA-894A previously received orphan drug status from the FDA. That designation aims to accelerate the development of therapies for rare diseases, defined in the U.S. as those affecting fewer than 200,000 people, by providing benefits such as tax credits, exemption from certain FDA fees, and seven years of market exclusivity if the treatment is approved.

Vanda stated that it is “advancing development of its investigational therapy for CMT2S and will continue to work closely with the FDA regarding the development program.”