The New Montana Right‑to‑Try Framework
In early 2024 the Montana Department of Health and Human Services finalized a set of rules that dramatically broaden the state’s “right‑to‑try” (RTT) pathway. Where the original 2015 statute limited access to unapproved medicines to terminally ill adults, the 2023 amendment—and the 2024 rulebook—extend eligibility to non‑terminal patients of any age provided the investigational product has completed a Phase I clinical trial.
Key components of the revised framework:
- Experimental Treatment Review Board (ETRB) – a standing panel that evaluates safety data, trial status, and the medical justification for each request.
- Application timeline – the first two petitions are slated for review within weeks, setting a precedent for how quickly the process can move.
- Commercial pathway – the law clarifies how clinics may sell or administer the experimental product, a detail that was vague in earlier versions.
The changes were motivated by families like the De Vaults, whose three‑year‑old son Brody suffers from creatine transporter deficiency (CTD), a disorder with no FDA‑approved therapy. Their advocacy underscores a broader national conversation about whether patients should be allowed to bypass the traditional FDA approval pipeline when the disease trajectory is dire and treatment options are nonexistent.
Clinical Landscape: Creatine Transporter Deficiency and Ceres’ Nasal Spray
What is CTD?
CTD is a rare, X‑linked metabolic disorder that impairs the brain’s ability to import creatine, a molecule essential for cellular energy storage. The resulting energy deficit manifests as:
- Severe developmental delays (speech, motor coordination)
- Profound muscle weakness
- Inability to communicate basic needs, leading to frustration and safety risks
Because the defect lies in the transporter protein, simply supplementing creatine orally is ineffective; the molecule cannot cross the blood‑brain barrier.
Ceres Brain Therapeutics’ Experimental Approach
French biotech Ceres Brain Therapeutics is pursuing a nasal‑spray formulation that delivers creatine directly to the olfactory epithelium, bypassing the defective transporter. The science is compelling:
- Pre‑clinical data: Mouse models of CTD showed restored brain creatine levels and improved motor performance after intranasal dosing.
- Phase I trial: Conducted in 48 healthy adults, the study explored safety across multiple dose levels. Results have not yet been published, but no serious adverse events were reported.
- Phase II plans: A combined CTD/ALS trial is slated for France later in 2024. The protocol will enroll patients with confirmed CTD, but the De Vaults have been told Brody is unlikely to qualify due to age and geographic constraints.
Because the product is not FDA‑registered and the manufacturing process does not meet U.S. Good Manufacturing Practice (GMP) standards, Ceres cannot currently participate in the federal Expanded Access (Compassionate Use) program. Montana’s RTT law, however, could provide a legal avenue for the De Vaults to import the spray—if the company is willing to assume the regulatory risk.
Legal and Ethical Crossroads
The Promise vs. the Peril
Proponents argue that the RTT
expansion offers a lifeline to families who have exhausted conventional options. Kris De Vault’s impassioned plea captures the urgency:
“I’m a full-grown human being. I’m capable of going to Vegas right now … blowing it all on the poker table, [or] I can go to the gun shop and buy a silenced [semi-automatic rifle] … how come I can’t make a decision to purchase a potential treatment that might change the entire trajectory of my son’s life?”
Yet critics, including Harvard’s Aaron Kesselheim, caution that Phase I data alone—collected in healthy adults—provide no assurance of efficacy or safety in pediatric patients with rare diseases. Kesselheim warns:
“Patients who want these kinds of treatments deserve them to be rigorously assessed so that [they] can better understand what they’re getting themselves into, and what they’re paying their hard-earned money for.”
The tension between autonomy and protection is further complicated by the lack of FDA oversight. Montana’s ETRB can review applications, but it lacks the authority to compel companies to participate. Ceres Brain Therapeutics’ CEO Thomas Joudinaud has expressed reluctance to engage with the program, citing concerns about potential FDA retaliation or reputational damage.
The Offshore Gamble: Próspera’s Unproven Therapies
With Montana’s pathway uncertain, the De Vaults are exploring alternatives—including a private clinic in Próspera, a special economic zone on the Honduran island of Roatán. Próspera operates under its own regulatory framework, allowing clinics to offer stem-cell therapies, gene editing, and other experimental treatments without the rigorous testing required in the U.S. or EU.
While Próspera markets itself as a hub for medical innovation, the scientific community remains skeptical. Many of the therapies offered lack peer-reviewed evidence, and some have been linked to severe complications, including tumor growth and immune reactions. For families like the De Vaults, however, the allure of hope—however tenuous—can outweigh the risks.
Kris De Vault acknowledges the gamble:
“I’m not naive. I know these clinics are selling hope. But when your child’s brain is literally starving for energy, and the clock is ticking, you’ll take any shot you can get.”
Regulatory Pushback and the Future of Right-to-Try
Montana’s expanded RTT law has reignited a national debate about the balance between patient autonomy and scientific rigor. Similar laws exist in 41 states, but most mirror the federal RTT statute, which is limited to terminally ill patients. Montana’s decision to include non-terminal children marks a significant departure—and one that could face legal challenges.
The FDA has not commented directly on Montana’s program, but the agency has historically opposed state-level expansions of RTT, arguing that they undermine the clinical trial process and expose patients to unproven risks. In 2018, the FDA issued guidance emphasizing that Expanded Access (compassionate use) remains the preferred pathway for patients seeking experimental treatments, as it includes safeguards like informed consent and adverse event reporting.
For now, the De Vaults—and other families in similar situations—are left navigating a patchwork of state laws, offshore clinics, and regulatory gray areas. The first two applications under Montana’s new rules will serve as a test case, offering a glimpse into whether the state’s approach can deliver on its promise of hope without sacrificing safety.
Conclusion: A Double-Edged Sword
Montana’s expanded right-to-try law represents a bold experiment in patient autonomy, one that could either accelerate access to life-changing treatments or expose vulnerable families to unproven risks. For Brody De Vault and others with rare diseases, the stakes couldn’t be higher. The coming months will reveal whether Montana’s ETRB can strike the right balance—or whether the state’s gambit will leave families like the De Vaults with more questions than answers.
As the debate rages on, one thing is clear: the traditional drug approval pipeline is too slow for those who need help now. Whether Montana’s approach is the solution—or a dangerous detour—remains to be seen.
FAQ
1. What is Montana’s new right-to-try law?
Montana’s expanded right-to-try law allows non-terminally ill patients, including children, to access experimental drugs that have completed Phase I clinical trials, provided they are reviewed by the state’s Experimental Treatment Review Board (ETRB). The original 2015 law was limited to terminally ill adults.
2. Who qualifies under the new rules?
Eligibility is open to:
- Patients of any age (including children).
- Those with serious or life-threatening conditions (not necessarily terminal).
- Individuals for whom no FDA-approved treatment exists.
- The experimental drug must have completed Phase I trials (safety testing in healthy adults).
3. How does the application process work?
- Patients or their guardians submit an application to the ETRB, including:
- Medical records documenting the condition.
- A physician’s statement supporting the request.
- Evidence that the drug has completed Phase I trials.
- The ETRB reviews the application for safety and medical justification.
- If approved, the patient (or their family) can purchase the drug directly from the manufacturer or a licensed clinic.
4. Why can’t Brody De Vault access Ceres’ drug through the FDA?
- The drug is not FDA-registered and is manufactured in a facility that does not meet U.S. Good Manufacturing Practice (GMP) standards.
- The FDA’s Expanded Access (Compassionate Use) program requires compliance with these standards, which Ceres does not currently meet.
- Montana’s law bypasses these requirements, but the company must still agree to participate.
5. What are the risks of using unapproved drugs?
- No guarantee of efficacy: Phase I trials only test safety in healthy adults, not effectiveness in patients.
- Unknown side effects: The drug may cause harm, especially in children or those with rare diseases.
- False hope: Families may spend significant time and money on treatments that ultimately fail.
- Regulatory consequences: Companies participating in state RTT programs risk FDA scrutiny or penalties.
6. What is Próspera, and why are families considering it?
Próspera is a private city/special economic zone in Honduras with its own regulatory framework. Clinics there offer unproven stem-cell therapies, gene editing, and other experimental treatments without the rigorous testing required in the U.S. or EU. Families like the De Vaults are drawn to Próspera because it provides faster access to therapies, but the lack of oversight raises serious safety concerns.
7. What happens next for Brody De Vault?
- The De Vaults are awaiting the ETRB’s review of their application for Ceres’ nasal spray.
- If denied, they may pursue alternative routes, including:
- Traveling to Próspera, Honduras, for unproven therapies.
- Advocating for changes to FDA regulations to allow expanded access.
- Exploring clinical trials in other countries (e.g., France, where Ceres’ Phase II trial is planned).
8. How can other families access experimental treatments?
- FDA Expanded Access: For terminally ill patients, the FDA’s Compassionate Use program may provide access to investigational drugs. Requires a physician’s request and manufacturer cooperation.
- Clinical Trials: Search ClinicalTrials.gov for ongoing studies.
- State Right-to-Try Laws: Check if your state has an RTT law and whether it applies to your condition.
- Offshore Clinics: Some families travel to countries with looser regulations, but this carries significant risks.
9. What are the arguments for and against Montana’s law?
For:
- Patient autonomy: Families should have the right to try unproven treatments when no alternatives exist.
- Speed: Traditional FDA approval can take years, which is too slow for patients with rare or degenerative diseases.
- Hope: Even a small chance of benefit may be worth the risk for desperate families.
Against:
- Safety concerns: Phase I data does not prove efficacy or safety in patients, especially children.
- Exploitation risk: Unscrupulous companies may take advantage of vulnerable families.
- Undermines clinical trials: If patients can access drugs outside trials, fewer may enroll in studies, slowing scientific progress.
10. Where can I learn more?
- Montana Department of Health and Human Services: dphhs.mt.gov
- FDA Expanded Access Program: fda.gov/expandedaccess
- Ceres Brain Therapeutics: ceresbrain.com
- Próspera: prospera.hn
Source: Original Article