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Who Writes the Rules for CMT Drug Trials?

Dan Knauss

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Line drawing of a balance scale tipped down toward a stack of coins on one side, with a page of written rules lifted on the other.

The first framework for designing CMT drug trials was written by patient charities, clinicians and drug companies, including two companies a co-authoring charity has money in — the CMTA. The FDA took part at first, then withdrew. The published paper carries no public statement of who has a financial stake in the outcome.

In August 2026 the Journal of the Peripheral Nervous System published “Clinical Development of Therapies for Charcot–Marie–Tooth Disease: Recommendations for Trial Design, Endpoints, and Regulatory Pathways.” Press coverage called it the field’s first consensus framework for CMT trials. It tells drug companies how to design studies, which patients to enrol, what to measure, and how to make the case for approval to the US Food and Drug Administration. Its recommendations are not FDA rules, but they will likely shape what reaches CMT patients, in the US and, the authors say, elsewhere: “the recommendations of this manuscript may be applied globally.”

So it’s worth asking who wrote it, and what they have riding on it.

Who Wrote It

The paper comes from a coalition called ToPIC: CMT (“Together Patients, Industry and Clinicians”). Its steering committee includes staff of four patient charities: Sue Bruhn and Katherine Forsey of the Charcot-Marie-Tooth Association (CMTA), Brian Lin of the Muscular Dystrophy Association, Allison Moore of the Hereditary Neuropathy Foundation and Susan Ruediger of the CMT Research Foundation. Ruediger, who co-founded the foundation and is its chief executive, was the CMTA’s director of development for eight years before that. The foundation’s other co-founder and chair, Patrick Livney, was the CMTA’s chief executive. So three of the five charity representatives have worked for the CMTA.

Two of the companies at the table are companies the CMTA has money in.

Three other members come from outside the charities. The paper lists Rebekah Fleming and Shannon Strom as independent researchers in Durham, North Carolina, and Susan McCune with Scendea, a drug-development consultancy. The CMTA’s own summary says Strom coordinated the effort. The paper doesn’t mention that Aerogen Pharma, a drug company, lists her as its senior vice president of regulatory affairs. The clinician authors are Charles Abrams, Joshua Burns, Vera Fridman, David Herrmann and Michael Shy.

Most of those clinicians are part of the CMTA’s own circle. Shy sits on the CMTA’s board and co-chairs its Clinical Expert Board. Burns, Fridman and Herrmann are on that board too, and Herrmann also sits on its Therapy Expert Board. Herrmann’s university, Rochester, received $1,045,708 from the CMTA in 2025, its largest grant that year. The return reports that figure for the university as a whole, not for any one researcher (see Who Is Behind the CMTA?).

Then there is the “development group” listed in the paper’s appendix:

CompanyRepresentative in ToPICCMT program or tie
NovartisPeggy Allred, Christina GreeleyLarge drug company
Actio BiosciencesDavid GoldsteinABS-0871, a CMT2C drug; Jazz Pharmaceuticals bought Actio in September 2026 and is spinning the drug out into a new company
Alesta TherapeuticsBenit MaruCMT drug developer
NMD PharmaThomas Holm PedersenNeuromuscular drug developer
Elpida TherapeuticsTerry PirovolakisThe CMTA holds a $150,000 promissory note (a loan) from Elpida
Armatus BioRachel SalzmanThe CMTA holds Armatus preferred stock carried at $253,066
Sources: ToPIC:CMT appendix in Abrams et al. 2026; CMTA audited financial statements for 2025; Jazz Pharmaceuticals and Actio Biosciences announcements. The CMTA’s summary also lists Applied Therapeutics and Thermo Fisher Scientific among the pharmaceutical partners.

Two of the companies at the table are companies the CMTA has money in. Its 2025 audit lists preferred stock in Armatus Bio carried at $253,066, an equity stake, and a $150,000 promissory note from Elpida Therapeutics, which is a loan. These are among four private holdings carried at $751,829; none trades publicly, so the figures are the CMTA’s own valuations. (The fourth holding is Shark Tooth Biotech, a company founded by a CMTA director.) If those companies’ drugs advance, the Armatus stake can gain value and the Elpida loan becomes likelier to be repaid.

What the Paper Doesn’t Say

The published full text has no public conflict-of-interest statement. I checked the online full text again on October 23, 2026: it has sections on funding and data availability, but nothing that declares the authors’ or organizations’ financial interests. The authors may have submitted disclosures to the journal privately; the absence of a public statement does not establish whether they did. I asked the journal’s editors about this on October 13, requesting a reply by October 23. No reply had been received when I checked on October 23. The only funding line says open access was paid for by the CMT Research Foundation. It doesn’t say who paid for the coalition’s work, its meetings or its coordinator.

Medical journals ask authors to declare financial ties because readers can’t weigh a recommendation without knowing who benefits from it. Here, a reader would not learn from the paper that a charity whose chief executive and chief research officer are authors holds equity and debt in companies whose representatives sat in the development group, or that several clinician authors advise that same charity.

The harder questions are about who decides, and what evidence has to follow.

The journal’s own masthead adds another layer. One of the paper’s authors, Joshua Burns, is an associate editor of the Journal of the Peripheral Nervous System, responsible for its CMT section. Two other authors, Vera Fridman and Steven Scherer, sit on its CMT editorial board, alongside CMTA director John Svaren. Charlotte Sumner, a member of the CMTA’s Scientific Advisory Board, is on the journal’s advisory board as an officer of the Peripheral Nerve Society. Overlap like this is common in a small field, and it doesn’t show that the paper was handled improperly. But it is one more reason readers need to know how the manuscript was reviewed, and who stepped aside. My October 13 inquiry to the journal’s editors also asked how editorial handling and peer review were managed and whether editors with relevant connections were recused.

The regulator’s role is limited too. The CMT Research Foundation’s Susan Ruediger told Clinical Leader that the FDA was involved early on but could no longer take part after the 2025 staff cuts at the Department of Health and Human Services, so the coalition published in a journal instead. The “consensus” is among charities, clinicians, regulatory specialists and industry. It is not an agreement with the FDA.

What It Recommends

Much of the paper is sensible, and some of it is admirably candid. It says randomized placebo-controlled trials “generally represent the most efficient approach” and warns that with historical controls “only large treatment effects are likely to be convincing.” Patient-reported outcomes, remote assessments and avoiding needless placebo exposure are all reasonable goals in a rare, slowly progressive disease.

Its more flexible recommendations come with conditions, and the conditions matter as much as the flexibility:

  • Fewer placebo groups. Single-participant designs and external or historical controls “may constitute adequate and well-controlled studies.” A single-participant design compares a patient with their own baseline; it is not necessarily a trial of one person. Still, CMT progresses slowly and its functional tests are noisy and effort-dependent, which is where comparisons without a concurrent control are most easily fooled.
  • Enrolling by symptoms, not genes. The paper favours enrolling by clinical features across subtypes, except for therapies that target a specific mutation. If a subtype wasn’t studied, it says the label could still include it where extrapolation is “scientifically justified,” which in its terms means a mechanistic case for why the drug should work there too.
  • Treating children early. It recommends “initiating therapy at the youngest age that is scientifically and ethically justified,” and discusses moving through age groups, including adolescents, in stages.
  • Biomarkers. The paper distinguishes markers that show a drug reached its target from markers that predict clinical benefit, and says some, such as neurofilament light chain, PMP22 and MRI muscle fat, “may serve as surrogate endpoints to support accelerated approval.” One of its own authors, the MDA’s Brian Lin, told NeurologyLive that none is yet a regulatory-grade surrogate, and called PMP22 “probably the furthest from regulatory validation.”
  • Shared safety data. Sponsors “may leverage safety data” from one CMT subtype for another, and from approved products on the same technology platform, where exposures are comparable and the platform is one regulators have designated.
  • Flexibility. “Regulatory flexibility should be exercised,” the paper says, citing patients’ willingness to accept risk.

Read with its conditions, the paper is more careful than a list of headlines suggests. The harder questions are about who decides. Who judges whether an extrapolation is “scientifically justified,” or a child’s exposure “ethically justified”? How much uncertainty is acceptable at approval, and what evidence has to follow? Accelerated approval has delivered real drugs. It has also left drugs on the market that later failed to show benefit, and patients and public insurers carried the cost. With a slow disease, patients have a lot to lose from a drug that is expensive, risky and doesn’t work.

The Patient Voice

The paper leans heavily on patient input: what patients want, how much risk they will tolerate. The CMTA also arranges much of that input. On October 20 it will host a patient listening session with the FDA on CMT2C, a rare form caused by variants in the TRPV4 gene. The FDA’s rules for these sessions are real safeguards: industry does not attend, the discussion is not about any specific drug, and the sessions are informal and non-binding.

There is a CMT2C drug in development: Actio Biosciences’ TRPV4 inhibitor ABS-0871, which entered a Phase 1 trial in 2025, the year Actio raised $66 million. Jazz Pharmaceuticals completed its purchase of Actio in September 2026, and said ABS-0871 would go to a new, separate company in which Jazz keeps a minority stake. Who will develop it from here isn’t public. The CMTA promoted the trial, held a patient focus group with Actio in 2023, and Actio’s David Goldstein sat in ToPIC’s development group.

That focus group is worth reading, because it complicates any simple story. Its report describes a small group: 14 people answered the survey and nine more spoke at the meeting. Participants were willing to accept some risk, but one worried about dying from a treatment. Some were ambivalent about a cure; one said, “I’m ok with just stopping it from getting worse.” Travel was a real barrier, and one person worried about privacy. That is not a one-note story of courage. The question for October 20 is not whether patients’ testimony is genuine. It is who recruits and prepares the speakers, and whether anyone with a drug in the pipeline has a hand in that.

The numbers need explaining too. The CMTA estimates about 2,500 Americans have CMT2C. The ToPIC paper, co-written by the CMTA’s chief executive and research chief, says nearly all CMT2 types other than CMT2A have “likely fewer than 1500 US patients for each genetic subtype.” The two figures may rest on different definitions or methods. The CMTA should say how it reached its estimate.

The framing of patient stories matters as well. For CMT Awareness Month this September, the CMTA’s #ItTakesNerve campaign asked for stories of courage: “Every person with CMT has a story about a time they had to dig deep and do the thing anyway.” That is the overcoming story, the kind that makes patients look brave and a cure look urgent. The Hereditary Neuropathy Foundation’s #ThisIsCMT campaign took a different line: “There is no right CMT story.” HNF has industry ties of its own, though; its TRIAD partnership lists Actio, Elpida and NMD Pharma among its partners. Every organization that shapes what regulators hear should meet the same disclosure standard.

What Should Happen

None of this means anyone acted in bad faith. Patient charities partnering with industry is normal now, and families with a child getting worse want treatments fast. That is exactly why the rules need to be written in the open, with every financial tie on the table.

At a minimum:

  1. The authors should publish a full conflict-of-interest statement, including the CMTA’s holdings in Armatus Bio and Elpida Therapeutics and any payments from participating companies to authors or their organizations.
  2. ToPIC should disclose who funded its work, its meetings and its coordinator.
  3. ToPIC should describe how it reached consensus: who drafted each recommendation, how disagreements were settled, and whether members with a financial interest stepped aside from recommendations that affect it.
  4. For each flexible pathway, the paper’s supporters should say what evidence must follow an accelerated approval, who checks it, and what happens to a drug if confirmatory studies fail.
  5. Organizations that run FDA listening sessions should say how speakers are recruited and prepared, which companies have drugs in development for that condition, and whether any of them funds the organization.
  6. Regulators, here and in Canada, should read the paper as recommendations from interested parties, to be weighed alongside independent review.

I have put these questions to the CMTA and the journal’s editors. As of my October 23 check, the journal had not replied to my October 13 inquiry. I will add any later response. If you know more, tell me.

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