GM1 Clinical Trials Guide

Last updated: May 2026 | Data current at ClinicalTrials.gov as of May 5, 2026

Important note before you begin: This guide is a reference tool, not a substitution for medical guidance. Clinical trial eligibility is complex and individualized. Always discuss options with your specialist team before pursuing enrollment.

The following trials are currently active (recruiting or opening soon). They are organized by treatment approach.

Field	Details
Trial ID	NCT03952637 (clinicaltrials.gov/study/NCT03952637)
Status	Actively Recruiting
Phase	Phase 1/2
Sponsor	National Human Genome Research Institute (NHGRI), NIH
Principal Investigator	Dr. Cynthia Tifft, NIH Clinical Center, Bethesda, MD
For	GM1 Type I and Type II (children), ages 2 – 13
Location	NIH Clinical Center, Bethesda, Maryland
Contact	Jean M. Johnston, RN — (240) 515-1448 — johnstonjm@mail.nih.gov
Est. completion	January 2028

How it works: A single intravenous (IV) dose of an AAV9 viral vector delivers a working copy of the GLB1 gene, with the goal of restoring beta-galactosidase enzyme activity. Patients receive immune-modulating drugs (rituximab, sirolimus, methylprednisolone) before and after infusion to reduce immune response.

What to know: This is the only post-natal gene therapy trial currently enrolling for GM1. Published Phase 1/2 results (2024-2025, NEJM ) showed the therapy is safe and well tolerated, with biochemical improvement and neuroimaging stabilization in Type II patients. The NIH trial continues as an independent investigator-led study at NHGRI.

Note on prior commercial programs: Several companies previously pursued AAV gene therapy programs for GM1 gangliosidosis, including Sio Gene Therapies, Passage Bio, and Lysogene, but none are currently advancing a GM1 gene therapy program. The NIH investigator-led trial is the active program in this space.

Field	Details
Trial ID	NCT07479953 (clinicaltrials.gov/study/NCT07479953)
Status	Not Yet Recruiting (Opening June 2026)
Phase	Phase 1
Sponsor	Dr. Tippi Mackenzie, University of California San Francisco
For	GM1 Type I and Type II fetuses (diagnosed prenatally at 28-35 weeks gestation)
Location	UCSF (specific site to be confirmed)
Est. completion	Long-term follow-up through 2055

How it works: AAV9-GLB1 is administered intravenously to the fetus in utero, before birth. The theory is that earlier treatment — before neurological damage accumulates — may achieve better outcomes, particularly for Type I.

What to know: This is a first-in-human prenatal gene therapy trial for GM1. Families must have a fetus already diagnosed prenatally (via CVS, amniocentesis, or cordocentesis) between 28-35 weeks gestation. The mother must have low anti-AAV9 antibody titers. This is a very small trial (5 participants), and each case must be reviewed and accepted by an enrollment advisory board. It is not yet accepting patients. Check ClinicalTrials.gov for enrollment contact details as the trial opens.

Nizubaglustat is an oral drug being developed by Azafaros A.G. that works by reducing the production of GM1 ganglioside, lessening the burden on a body that cannot break it down efficiently. This approach is called substrate reduction therapy (SRT).

Field	Details
Trial ID	NCT07082543 (clinicaltrials.gov/study/NCT07082543)
Status	Actively Recruiting
Phase	Phase 3
Sponsor	Azafaros A.G.
For	Late-infantile and juvenile forms of GM1 and GM2 gangliosidosis
Age	4 years and older
Design	18-month, double-blind, randomized, placebo-controlled
Randomization	2:1 (two participants receive drug, one receives placebo)

U.S. Sites Currently Recruiting: – UCSF Children’s Hospital and Research Center at Oakland, California — Veronica Cheung, CRC — 510-428-3885 — Veronica.Cheung@ucsf.edu – Mayo Clinic Children’s Center — Rochester,

Minnesota – Lysosomal Rare Disorders Research and Treatment Center – Fairfax, Virginia – Lauren Noll – 571-732-4655 – lnoll@ldrtc.org – Children’s Medical Center Dallas, Texas (not yet recruiting) – University of Minnesota Medical School – Minneapolis, Minnesota (not yet recruiting)

International Sites: Argentina, Australia, Brazil, Canada, Czech Republic, France, Germany, Italy, Netherlands, Portugal, Spain, Turkey, United Kingdom, and others.

Contact Azafaros: info@azafaros.com (Patient Advocacy) | medinfo@azafaros.com (Healthcare Professionals)

What to know: Nizubaglustat is taken as an oral dispersible tablet daily. This is a Phase 3 trial — the final stage of testing before the FDA considers approval. It targets late-infantile and juvenile forms, meaning it is designed for patients who developed symptoms between approximately ages 1-10. Phase 2 data showed preliminary safety signals and biochemical activity.

Treatment	Phase	Target Population	Status
AAV9-GLB1 gene therapy (IV, post- natal)	Phase 1/2	Type I and II	Recruiting: NIH, Bethesda MD
AAV9-GLB1 gene therapy (IV, prenatal)	Phase 1	Type I and II (in utero)	Opening June 2026: UCSF
Nizubaglustat oral SRT	Phase 3	Late-infantile and Juvenile	Recruiting: Multiple sites worldwide
ICV Enzyme Replacement Therapy (ERT)	Preclinical	TBD	In development: CGM1-01 program

One of the most important things families new to the clinical trial world need to understand is this:

A clinical trial is a scientific study. It is not a way to purchase or access a treatment that already exists.

This distinction matters deeply. Misunderstanding it can lead to heartbreak, financial harm, or missed opportunities.

A clinical trial is a carefully designed research study conducted in human volunteers to answer specific scientific questions about a potential therapy:

Is it safe? (Phase 1 focus) • Does it work, and at what dose? (Phase 2 focus) • Is it more effective than existing options, in a larger population? (Phase 3 focus) • What happens long-term after approval? (Phase 4)

Every clinical trial has a protocol — a detailed scientific plan specifying exactly who can participate, what will be given and when, and how results will be measured. Participants are research subjects, and their safety is protected by institutional review boards (IRBs) and federal law.

Common Misconception	Reality
“I’m paying to access a treatment”	Participation is always free. No one should ever pay to enroll. If someone asks for money, it is a scam.
“I’m guaranteed to get the drug”	Many trials are randomized — you may receive a placebo or standard of care. This is essential to generate scientific evidence.
“This treatment is proven to work”	Trials exist precisely because we don’t yet know if something works. Most investigational therapies do not ultimately get approved.
“I can customize what I receive”	Protocols are fixed. You cannot request a higher dose, skip a procedure, or modify the treatment plan.
“The trial is happening because the drug is ready”	Phase 1 trials often involve the very first doses ever given to humans. They exist to find the safe dose range.
“If I’m not enrolled, I’m being denied access”	Being excluded from a trial means you don’t fit the scientific criteria — it is not a refusal of care.

PRECLINICAL (Lab/Animal) –> PHASE 1 –> PHASE 2 –> PHASE 3 –> FDA REVIEW –> APPROVED

Typical timeline: 6+ years preclinical, then 1-2 years per phase, plus 1-3 years FDA review.

Phase 1: “Is It Safe?” First time in humans. Small group (10-50 people), often adults first. Goal: establish safe dosing range and identify side effects. No expectation of therapeutic benefit — this is purely safety science. For rare diseases like GM1, Phase 1 and 2 are often combined (“Phase 1/2”).

Phase 2: “Does It Work, and at What Dose?” Larger group (50-300 people). Tests the treatment in the target patient population. Some trials are randomized with placebo control. Goal: preliminary evidence of efficacy and dose optimization.

Phase 3: “Is It Consistently Effective?” Large, randomized, controlled trial (hundreds to thousands). Definitive evidence for or against FDA approval. Gold standard: double-blind, placebo-controlled. This is the final step before an approval decision.

Phase 4: “What Happens Long-Term?” Post-approval surveillance. Monitoring for rare side effects not seen in trials. Ongoing registry studies after a drug is on the market.

When families learn their loved one does not qualify for a trial, it can feel like being turned away from the only hope. But eligibility criteria exist for essential reasons:

Safety: Some exclusions protect people who might be harmed. For example, people with active infections may not safely receive gene therapy.

Scientific integrity: If the study population is too varied, the results become uninterpretable. Researchers need to isolate one variable at a time to know whether a treatment actually worked.

Regulatory requirements: The FDA will not accept data from studies without clear, consistent eligibility criteria. A trial that enrolls “anyone who wants to try it” produces data the FDA cannot use, which means the drug never gets approved, hurting everyone in the future.

Being excluded is not a denial of care. It is science protecting its integrity, and ultimately protecting patients.

For GM1, trials may specifically need patients with: – A certain type (e.g., Type 2, not Type 1) – A certain disease stage (not too early, not too advanced) – Specific biomarker levels or genetic variants – A defined age range

These requirements reflect the science of what a given therapy might reasonably help, and what the trial can actually measure. Enrolling patients unlikely to benefit or in whom outcome measures won’t be detectable can invalidate a trial even if the drug works for others.

“Compassionate use” (the informal term) and “expanded access” (the FDA’s official term) refer to pathways that allow patients to access investigational drugs outside of a clinical trial when:

The patient has a serious or life-threatening condition 1. There is no comparable or satisfactory alternative treatment available 2. The patient cannot enroll in a clinical trial 3. The potential benefit justifies the risks 4.

The FDA regulates three forms of expanded access: – Individual patient expanded access (one patient at a time) – Intermediate-size population (small group with similar needs) – Treatment IND/protocol (large-scale, used when awaiting approval)

Condition	Why Expanded Access Becomes Possible
Phase 2/3 safety data is established	The manufacturer has enough safety data to responsibly manage risks in non- trial patients
Drug is scalable and manufacturable	The drug can be made in sufficient quantity to treat additional patients
FDA has reviewed a safety package	An IND covering expanded use is in place

Condition	Why Expanded Access Becomes Possible
Trial enrollment is closed or complete	No trial slot is available, yet compelling evidence exists
Drug is pending approval (Phase 3 complete)	Pre-approval access while awaiting final FDA decision

This is one of the most common and heartbreaking questions families ask: “The trial is full. The trial doesn’t include my child’s type. Can we just get the gene therapy somehow?”

The honest answer is: almost certainly not, for several interconnected reasons.

1. Manufacturing Constraints — Each Dose Is Made for One Person

AAV gene therapy vectors are biologics, not pills. Each dose must be: Manufactured specifically for the patient (weight-based dosing) -Tested for purity, potency, and sterility before release – Stored and transported under strict conditions, often ultra-cold – Administered in a specialized medical center with immediate access to intensive care

A single dose of an AAV gene therapy can cost $50,000 to $500,000 or more to manufacture at clinical scale, and global supply is measured in single-digit doses per year for most early-phase programs. There is literally no “extra” supply.

2. AAV Can Only Be Given Once — The Immune Problem

When AAV enters the body, the immune system recognizes it as foreign and produces antibodies against that specific AAV serotype. This means:

A person who receives AAV9 cannot receive another AAV9-based therapy ever again. Their immune system will destroy it before it can work. This is a permanent, irreversible consequence. If a compassionate use dose does not work (because the patient was too advanced, the wrong subtype, or the wrong dose), the patient is permanently closed off from future trials using the same vector.

This makes compassionate use an especially high-stakes, one-shot decision, not something to do casually or out of desperation.

3. Data Integrity and Regulatory Risk

For a clinical trial to produce results the FDA can rely on, every dose must be tracked, monitored, and reported with rigorous protocol compliance. Patients who receive expanded access are not enrolled in the trial, not followed on the trial protocol, and not generating comparable data.

If a sponsor provides too many compassionate use doses, it can contaminate the regulatory dataset and jeopardize the entire IND. For ultra-rare diseases like GM1 where the entire world patient population might fit in a large room, even a handful of off-protocol doses can have outsized statistical consequences and delay or derail approval for everyone.

4. Extreme Cost with No Reimbursement

An approved gene therapy (like Zolgensma for SMA) can cost $2 to $3 million per patient. During development, there is no insurance coverage, no government reimbursement pathway, no established price, and no financial

mechanism for the sponsor to recover costs. Providing compassionate use means the manufacturer absorbs the full manufacturing, testing, shipping, and administration costs with zero revenue, while also taking on full liability for adverse events in an uncontrolled setting.

5. Legal and Liability Exposure

Outside a clinical trial, sponsors lose the specific legal protections that trials provide. A serious adverse event in a compassionate use patient can expose the sponsor to enormous liability — and for a small academic program or startup biotech, potentially program-ending consequences.

Small molecules and oral drugs are much more amenable to expanded access because: They are synthesized pharmaceuticals that can be manufactured at scale. They can be dosed using standard tablet formulations. They do not trigger the same permanent immune consequences as AAV – A Phase 3 program generates far more safety data than Phase 1/2

Even when a specific trial is not available, there is meaningful and important work to do. The Cure GM1 Foundation is at the center of it.

The Cure GM1 Community Census at curegm1.org/census is one of the most important things any family can do, and it takes only minutes.

The census collects information about GM1 patients worldwide: diagnosis type, age of onset, symptoms, current treatments, geographic location, and more. This data directly shapes research priorities, helps identify trial-ready patients, and gives pharmaceutical companies and researchers the population evidence they need to invest in GM1 programs.

When a company evaluates whether to develop a drug for GM1, one of their first questions is: how many patients are there, and where? The census answers that question. Every registration is an act of advocacy.

Register: curegm1.org/census

The Cure GM1 Foundation has partnered with CombinedBrain to establish a biobank for GM1 patients. Biobanked samples include blood and urine. Specimens are an essential resource for drug developers validating biomarkers, designing assays, and demonstrating regulatory-grade evidence of target engagement.

Biobanking is one of the most direct and lasting contributions a family can make to GM1 research. Contact Cure GM1 at info@curegm1.org to learn how to participate.

The Cure GM1 Foundation runs an active community where families, researchers, and advocates connect, share experience, and support one another through every stage of the GM1 journey.

Website: curegm1.org • Email: info@curegm1.org • Phone: (510) 306-2460

Whether you are newly diagnosed, years into the journey, or a family who has experienced loss, there is a place for you here. No family should navigate GM1 alone.

Cure GM1 runs programs that directly advance the research landscape:

Patient-Focused Drug Development (PFDD): Cure GM1 organized and submitted patient and caregiver testimony to the FDA to shape how drugs are evaluated for GM1. This work established an evidentiary record of what outcomes matter most to the GM1 community. This meeting is a record that regulators and developers continue to reference.

World Symposium and Annual GM1 Community Conference: Cure GM1 actively attends and presents at major scientific conferences, including the World Symposium on Lysosomal Disease, submitting abstracts and posters to advance awareness of GM1 and share the community’s research priorities with the broader rare disease field. Cure GM1 also hosts its own annual conference and virtual fundraising events, bringing families, researchers, and advocates together to share progress and build momentum.

The GM1 treatment pipeline is moving faster than at any prior point in history. ERT programs, next-generation gene therapy vectors, and new SRT agents are in active development. Cure GM1 publishes regular updates on the pipeline so families don’t miss developments that matter.

Subscribe to the Cure GM1 newsletter at curegm1.org, and follow the Foundation’s social media channels for real-time updates on trial openings, research publications, and advocacy opportunities.

Specialized LSD centers often have the best access to emerging trials before public announcement — because they are designated trial sites. Key centers for GM1 include:

NIH Clinical Center, Bethesda, Maryland (Dr. Cynthia Tifft) • UCSF Children’s Hospital, Oakland / San Francisco, California • University of Minnesota Pediatric Genetics and Metabolism, Minneapolis • Mayo Clinic Children’s Center, Rochester, Minnesota • Lysosomal Rare Disorders Research and Treatment Center, Fairfax, Virginia •

Organization	Contact	Notes
NIH / NHGRI (Gene Therapy)	Jean M. Johnston, RN — (240) 515-1448 — johnstonjm@mail.nih.gov	NIH GM1 gene therapy trial
Azafaros (Nizubaglustat)	info@azafaros.com	Trial eligibility and sites
UCSF Oakland (Nizubaglustat site)	Veronica Cheung, CRC — 510-428-3885 — Veronica.Cheung@ucsf.edu	Phase 3 enrollment, Bay Area
Lysosomal Disease Research Center (VA)	Lauren Noll — 571-732-4655 — lnoll@ldrtc.org	Phase 3 enrollment, East Coast

Resource	Contact
Cure GM1 Foundation	info@curegm1.org — (510) 306-2460 — curegm1.org
GM1 Community Census	curegm1.org/census
GM1 Biobank (via CombinedBrain)	info@curegm1.org
NORD (National Organization for Rare Disorders)	rarediseases.org

Resource	URL
ClinicalTrials.gov	clinicaltrials.gov (search: “GM1 gangliosidosis”)
ASGCT Gene Therapy Trial Browser	patienteducation.asgct.org
Cure GM1 Treatment Landscape Blog	curegm1.org/gm1-gangliosidosis-treatment/

How Clinical Trials Work (FDA): fda.gov/patients/clinical-trials-what-patients-need-know • Gene Therapy Patient Education (ASGCT): patienteducation.asgct.org/understanding-cell-gene-therapy • FDA Expanded Access Overview: fda.gov/patients/learn-about-expanded-access-and-other-treatment- • options

This guide was compiled in May 2026 based on data from ClinicalTrials.gov and public sources. The GM1 trial landscape evolves rapidly. Always verify current trial status at clinicaltrials.gov and consult with your specialist team. Questions about this document: info@curegm1.org