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Sunlight on the CMTA

One Patient, One Drug—and a Possible Voucher

Dan Knauss

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Line drawing of a single capsule beside a ticket stub marked with a dollar sign.

In July 2026 the US Food and Drug Administration gave a rare pediatric disease designation to VCA-894A, an experimental drug from Vanda Pharmaceuticals for an ultrarare form of CMT known as CMT2S, according to Charcot-Marie-Tooth News.1 CMT2S is a progressive inherited neurological disorder affecting fewer than 1 in 1 million people worldwide.2

VCA-894A already had orphan drug status.3 If the drug is approved, its pediatric designation could also earn Vanda a priority review voucher, the kind of voucher another company, Ultragenyx, recently agreed to sell for $210 million. If VCA-894A becomes available, it will be a custom drug made for a single patient, a promising experimental approach that public incentives like these are meant to encourage.

What is an “orphan drug?”

In the United States, the Orphan Drug Act defines a rare disease or condition as one that affects fewer than 200,000 people in the US, or more than 200,000 when there is no reasonable expectation that the cost of developing a drug for it will be recovered from US sales.4 In the European Union, the EMA defines an orphan drug as a product for a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the EU.5

A drug for one patient, approved on very little data, could be worth more to its developer as a ticket than as a treatment.

Historically, pharmaceutical companies neglected, or “orphaned,” potential treatments for these conditions because small patient populations made them unprofitable to develop. The Orphan Drug Act answered with incentives: a tax credit for clinical testing costs, seven years of market exclusivity after approval, research grants, and waived FDA application fees.6 Governments could go further, for example with a government-run enterprise, like a Canadian Crown corporation, that bears the costs and effort of research and development itself. Either way, much of the early risk and cost moves to taxpayers. The profits, in a successful outcome, flow to private drug companies. Without any guarantee of success, can the tradeoff be worthwhile to rare disease patients and the public?

A Drug for One Person

VCA-894A is an antisense oligonucleotide, a short, made-to-order strand of genetic material that changes how a gene’s instructions are read. It targets one splice variant in the IGHMBP2 gene, found in a single patient with CMT2S, a severe form that usually starts in early childhood with progressive weakness, wasting and sensory loss. It is built for that variant, not for CMT2S in general.7 According to the report, the variant has not been seen in any other patient.8

Vanda’s published preclinical work goes well beyond a single lab test. In cells grown from the patient, the drug raised levels of the deficient protein by more than half.9 It was also tested in a lab-grown model of the junction between nerve and muscle, and a three-month study in rats found it well tolerated when injected into the spinal fluid.10 None of that shows the drug helps a person.

One person has been treated, in a Phase 1/2 trial (NCT07223632) that began in May 2025.11 The trial measures safety, tolerability and motor function. No efficacy results have been reported.

Custom antisense drugs can work. The best-known case, milasen, was developed in 2017 for a single child with Batten disease and first given in January 2018 under an investigational protocol; it was never approved for sale.12 A nonprofit, n-Lorem, now makes such drugs for people with “nano-rare” variants and says it provides them “for free, for life,”13 though the treating hospital must cover the cost of giving the drug. For a family facing a disease like CMT2S, a treatment designed around one person’s own variant is extraordinary.

Why the Designation Matters

The rare pediatric disease designation does something the news report mentions only in passing. If the drug is approved through a qualifying application, the company may receive a priority review voucher. The voucher doesn’t speed up this drug, and it doesn’t lower anyone’s approval standard. Its holder can redeem it to have a different drug reviewed in six months instead of ten.14 Vouchers can be sold, and they are worth a great deal: on October 7, 2026, Ultragenyx announced an agreement to sell one for $210 million, subject to closing conditions.15 Congress revived the program in its 2026 government funding bill after it had lapsed,16 and the FDA can now award vouchers until September 30, 2029.17

There is a wrinkle. The patient described in Vanda’s paper was 19.18 The law says a voucher-qualifying application must rely on “clinical data derived from studies examining a pediatric population” and on dosages “intended for that population.”19 CMT2S usually begins in childhood, which is how the drug qualified for the designation. How Vanda would meet the pediatric-data requirement is not clear from anything public. That doesn’t mean it can’t, but it is a question Vanda should answer.

The voucher was meant to reward companies for developing drugs for children with rare diseases, because those drugs rarely pay for themselves. Whether it does is disputed. In 2020 the US Government Accountability Office found that the few studies of voucher programs showed little or no effect on drug development, although all seven drug companies it interviewed said vouchers were a factor in their decisions.20 What is clear is that a drug for one patient, approved on very little data, could be worth more to its developer as a ticket than as a treatment. That is not a reason to stop. It is a reason to watch how approvals for one-patient drugs are decided, and whether the evidence required keeps pace with the money at stake.

The New Rules Point the Same Way

The CMT trial recommendations published this summer by patient charities, clinicians and drug companies endorse this path. They point sponsors to the FDA’s “plausible mechanism” framework for individualized treatments, built on very small trials plus supporting lab evidence, and they urge that “regulatory flexibility should be exercised” for diseases like CMT.21 That framework is set out in draft guidance the FDA issued on February 23, 2026, after this patient’s treatment began; it is not binding.22 I look at who wrote those recommendations, and what they have riding on them, in Who Writes the Rules for CMT Drug Trials?

For the few patients with variants like this one, flexibility may be the only way a treatment ever exists. For the much larger CMT population, the same flexibility applied to common subtypes could mean approving drugs on weaker evidence than patients deserve. The two cases should not be argued as one.

Questions That Matter More Than the Voucher

  • Will the patient keep receiving the drug after the trial ends, and who will pay for it?
  • If VCA-894A is approved, what will it cost, and who will be able to get it?
  • Will Vanda publish the patient’s outcomes in full, including any that are disappointing?
  • How does Vanda plan to meet the law’s pediatric-data requirement for a voucher?
  • If a voucher is awarded and sold, will any of the proceeds go toward treating the next patient with an ultrarare CMT variant?

If you know more about this program, tell me.

Notes

  1. Lobo, “FDA Awards Special Status.” ↩︎
  2. Orphanet lists CMT2S (ORPHA:443073) with a worldwide point prevalence below 1 in 1,000,000, based on about 35 reported cases or families. Orphanet, “Charcot-Marie-Tooth Disease Type 2S.” ↩︎
  3. The FDA granted the designation in June 2023. Vanda Pharmaceuticals, “Orphan Drug Designation Granted for VCA-894A.” ↩︎
  4. The 200,000 threshold was added in 1984; the original 1983 Act used only the cost-recovery test. 21 U.S.C. § 360bb(a)(2). ↩︎
  5. The EU definition has further conditions: there must be no satisfactory existing treatment, or the new product must offer significant benefit over it. Regulation (EC) No 141/2000, art. 3. ↩︎
  6. Orphan exclusivity is a regulatory protection, separate from patents: for seven years the FDA may not approve the same drug for the same rare disease. The tax credit was cut from 50 to 25 percent of qualified clinical testing costs in 2017. US Food and Drug Administration, “Designating an Orphan Product”; 21 U.S.C. § 360cc; 26 U.S.C. § 45C. ↩︎
  7. The patient has two different IGHMBP2 variants, one on each copy of the gene: the splice variant and a missense variant. VCA-894A is designed to correct only the splice variant. Smieszek et al., “Potential ASO-Based Personalized Treatment.” ↩︎
  8. Lobo, “FDA Awards Special Status.” ↩︎
  9. Smieszek et al., “Potential ASO-Based Personalized Treatment.” ↩︎
  10. The rat study gave the drug by lumbar injection to 80 animals. The highest dose caused short-lived signs such as abnormal gait and reduced activity, but the authors still set it as the dose with no observed adverse effect. Smieszek et al., “Potential ASO-Based Personalized Treatment.” ↩︎
  11. ClinicalTrials.gov lists a start date of May 13, 2025, and one participant. Primary outcomes are adverse events and two motor scales (RULM and HFMSE); a secondary outcome is IGHMBP2 RNA in spinal fluid and blood. Vanda announced the first dose on June 10, 2025. ClinicalTrials.gov, “NCT07223632”; Vanda Pharmaceuticals, “First Patient Dosed.” ↩︎
  12. Mila Makovec had CLN7 Batten disease. Her seizures became less frequent after treatment, but she died in 2021 at age 10. Kim et al., “Patient-Customized Oligonucleotide Therapy”; Rare Daily Staff, “Mila Makovec, Recipient of Bespoke ASO.” ↩︎
  13. n-Lorem Foundation, “Physicians.” ↩︎
  14. US Food and Drug Administration, “Priority Review.” ↩︎
  15. The voucher came from the FDA’s approval of Ultragenyx’s gene therapy for glycogen storage disease type Ia. The buyer was not named. Jacobus, “Ultragenyx to Sell Rare Pediatric Disease Priority Review Voucher.” ↩︎
  16. The program had stopped accepting new designations after December 20, 2024. The extension is Pub. L. 119-75, div. J, § 6604, enacted February 3, 2026. Incorvaia, “FDA’s Rare Pediatric Disease Voucher Program Revived.” ↩︎
  17. 21 U.S.C. § 360ff(b)(5). ↩︎
  18. The paper describes her symptoms at age 11 and says she was 19 when it was written. ClinicalTrials.gov lists the trial as open to children and adults. Smieszek et al., “Potential ASO-Based Personalized Treatment.” ↩︎
  19. The same definition also says a qualifying application must not seek approval for an adult indication. 21 U.S.C. § 360ff(a)(4)(D)–(E). ↩︎
  20. Six of the seven called the voucher one factor among several; one said it was pivotal to developing a particular drug. US Government Accountability Office, Drug Development: FDA’s Priority Review Voucher Programs. ↩︎
  21. The recommendations come from the ToPIC:CMT group (Together Patients Industry Clinicians versus CMT) and were published online in August 2026. Abrams et al., “Clinical Development of Therapies for Charcot–Marie–Tooth Disease.” ↩︎
  22. US Food and Drug Administration, Considerations for the Use of the Plausible Mechanism Framework. ↩︎

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