EPI-321
An investigational treatment for Facioscapulohumeral Muscular Dystrophy.
Drug facts
The same compound appears under different names depending on the context. Here is how to identify EPI-321 wherever you encounter it, plus the key facts at a glance.
- Generic name
- EPI-321
- Development code
- EPI-321
- Drug class
- AAV-delivered epigenetic editing therapy
- Manufacturer
- Epicrispr Biotechnologies
- How it's taken
- One-time intravenous infusion, in a trial only
An investigational one-time epigenetic editing therapy from Epicrispr Biotechnologies for facioscapulohumeral muscular dystrophy (FSHD), designed to silence DUX4, the gene that drives the disease[2][1].
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Where EPI-321 fits
EPI-321 is an experimental one-time epigenetic editing therapy from Epicrispr for FSHD, given by IV infusion to 12 adults in a Phase 1/2 study[5][1].
- No disease-modifying therapy for FSHD is approved, Epicrispr says[6].
- FSHD care today is supportive, and NORD describes physical therapy, exercise, ankle-foot braces for walking, breathing tests with night-time breathing support when needed, and for some people surgery to attach the shoulder blades to the chest wall[9].
- EPI-321's results so far come from Epicrispr's releases on a few patients, compared with outside natural history data and a computer model rather than a placebo group[6].
- People with FSHD can ask their neuromuscular doctor which FSHD studies are open and whether their FSHD type would qualify.
How EPI-321 works
FSHD weakens the muscles of the face, around the shoulder blades and in the upper arms[8]. Both types of the disease trace back to a stretch of DNA near the end of chromosome 4 called D4Z4, where heavy methylation, a chemical tag on DNA, normally keeps a gene called DUX4 switched off in most adult cells and tissues[8]. When that silencing fails, DUX4 turns on in muscle.
Epicrispr calls DUX4 the genetic driver of FSHD, and MedlinePlus Genetics says researchers think active DUX4 changes the activity of other genes in muscle cells, leading to weakness, though how it damages those cells is not known[8][4]. EPI-321 uses Epicrispr's GEMS platform to regulate gene activity without altering the underlying DNA sequence, and Epicrispr says it is designed to silence DUX4[4].
BioPharma Dive reported on August 11, 2026 that the therapy binds a specific area of DUX4 and adds a chemical change that suppresses production of the protein[7]. The therapy is packaged in a modified virus shell called AAVrh74, used only for delivery to muscle, and given once into a vein[1][6]. The trial measures DUX4 activity and the methylation of the D4Z4 region in muscle biopsies to check whether the switch-off is happening[1].
Clinical trial results
The Phase 1/2 study (NCT06907875) is an open-label, dose-escalation trial in adults aged 18 to 75 with genetically confirmed FSHD type 1, with no placebo group[1]. Its main measure is side effects, and its other measures, taken from muscle biopsies at 3 and 12 months, are the amount of therapy that reached muscle, DUX4 activity and D4Z4 methylation[1].
Epicrispr announced on July 7, 2026 that all 12 participants had been enrolled and dosed[5]. In June 2026, Epicrispr reported that the first 3 evaluable people in the lower dose group gained an average of about 370mL of lean muscle volume on MRI at 6 months, about 0.8 pounds, with individual gains of about 0.5 to 1.3 pounds[4].
On October 5, 2026, at the World Muscle Society congress, Epicrispr reported 6-month results for the first 6 people: upper body lean muscle volume rose 3.0%, against a 3.5% loss predicted by a computer model of matched patients that Epicrispr calls a digital twin[6]. Epicrispr also reported that upper body strength on quantitative muscle testing rose 4.1%, against a 0.3% decline in matched patients from the ReSolve FSHD natural history study, and that elbow extension strength rose 8.1%[6].
These comparison groups were not treated in the same study, which makes the comparison weaker than one against placebo.
Main registered trial: NCT06907875 on ClinicalTrials.gov. Check it for the current status, sites and contacts before asking about enrollment.
Side effects and safety
Side effects are the primary outcome of the Phase 1/2 study, collected for up to 5 years after the infusion[1]. Epicrispr reported on January 8, 2026 that no serious or severe adverse events had been reported among the first 4 people dosed[3]. In June 2026 Epicrispr reported no serious adverse events among 9 people treated as of a May 12, 2026 data cutoff[4].
Its October 5, 2026 release says no serious adverse events related to EPI-321 were observed and calls the safety profile manageable[6]. Epicrispr has not published a list of milder side effects or described any steroid or immune-suppressing medicine given with the infusion. People with high levels of antibodies to the AAVrh74 shell cannot join the study[1].
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking EPI-321
Given once as an intravenous infusion in the trial[1]. Epicrispr treated 6 people at 2x10^13 vg/kg and 6 at 4x10^13 vg/kg[5]. Any approved dose would be set by an FDA label.
Development history
Epicrispr announced on April 3, 2025 that the FDA had cleared its application to start human testing, and said EPI-321 already held Fast Track, Rare Pediatric Disease and Orphan Drug designations[2]. ClinicalTrials.gov lists the Phase 1/2 study as starting on May 8, 2025[1]. By January 8, 2026, 4 people had been dosed, and Epicrispr reported trial clearances in New Zealand and Australia as well as the US[3].
Enrollment and dosing of all 12 participants were complete by July 7, 2026[5]. BioPharma Dive reported on August 11, 2026 that Epicrispr raised $90 million in a Series C round to advance EPI-321[7]. In its October 5, 2026 release, Epicrispr said it expects 12-month data on all participants in the second half of 2027[6]. ClinicalTrials.gov lists an estimated primary completion date of July 7, 2027[1]. Epicrispr has not announced a pivotal study design for EPI-321.
Explore Facioscapulohumeral Muscular Dystrophy trials
Common questions about EPI-321
▸What is EPI-321?
An investigational one-time epigenetic editing therapy from Epicrispr Biotechnologies for facioscapulohumeral muscular dystrophy (FSHD), designed to silence DUX4, the gene that drives the disease[2][1]. It is being tested in a Phase 1/2 study of 12 adults, and Epicrispr has reported early results only in its own releases and has not published them in a peer-reviewed journal[5][6]. Epicrispr says the FDA has given it Orphan Drug, Fast Track and Rare Pediatric Disease designations[2].
▸How does EPI-321 work?
FSHD weakens the muscles of the face, around the shoulder blades and in the upper arms[8]. Both types of the disease trace back to a stretch of DNA near the end of chromosome 4 called D4Z4, where heavy methylation, a chemical tag on DNA, normally keeps a gene called DUX4 switched off in most adult cells and tissues[8]. When that silencing fails, DUX4 turns on in muscle. Epicrispr calls DUX4 the genetic driver of FSHD, and MedlinePlus Genetics says researchers think active DUX4 changes the activity of other genes in muscle cells, leading to weakness, though how it damages those cells is not known[8][4]. EPI-321 uses Epicrispr's GEMS platform to regulate gene activity without altering the underlying DNA sequence, and Epicrispr says it is designed to silence DUX4[4]. BioPharma Dive reported on August 11, 2026 that the therapy binds a specific area of DUX4 and adds a chemical change that suppresses production of the protein[7]. The therapy is packaged in a modified virus shell called AAVrh74, used only for delivery to muscle, and given once into a vein[1][6]. The trial measures DUX4 activity and the methylation of the D4Z4 region in muscle biopsies to check whether the switch-off is happening[1].
▸What are the side effects of EPI-321?
Side effects are the primary outcome of the Phase 1/2 study, collected for up to 5 years after the infusion[1]. Epicrispr reported on January 8, 2026 that no serious or severe adverse events had been reported among the first 4 people dosed[3]. In June 2026 Epicrispr reported no serious adverse events among 9 people treated as of a May 12, 2026 data cutoff[4]. Its October 5, 2026 release says no serious adverse events related to EPI-321 were observed and calls the safety profile manageable[6]. Epicrispr has not published a list of milder side effects or described any steroid or immune-suppressing medicine given with the infusion. People with high levels of antibodies to the AAVrh74 shell cannot join the study[1].
▸How is EPI-321 taken?
▸Is EPI-321 FDA approved?
EPI-321 is currently in phase 2 clinical trials for Facioscapulohumeral Muscular Dystrophy. It has not yet received FDA approval.
▸Is EPI-321 FDA approved?
No. EPI-321 is an experimental epigenetic editing therapy in a Phase 1/2 study, and the FDA has not approved it for any use.
Designations: Orphan Drug, Fast Track and Rare Pediatric Disease, according to Epicrispr.
Next: Epicrispr said on October 5, 2026 that it expects 12-month data on all participants in the second half of 2027.
Source: Epicrispr, October 5, 2026
▸What results has EPI-321 shown in FSHD?
Epicrispr reported that upper body lean muscle volume rose 3.0% at 6 months in the first 6 people treated, against a 3.5% loss predicted by a computer model of matched patients.
Strength: Epicrispr reported a 4.1% gain in upper body muscle testing, against a 0.3% decline in matched patients from a natural history study.
Safety: Epicrispr reported no serious adverse events related to EPI-321.
Caveat: The study has no placebo group, and the results come from company releases, not a published paper.
Source: Epicrispr, October 5, 2026
▸Can I join an EPI-321 trial?
Not right now. ClinicalTrials.gov lists the EPI-321 Phase 1/2 study as active and no longer recruiting.
Who it enrolled: Adults 18 to 75 with genetically confirmed FSHD type 1 who walk without a walker or wheelchair.
Where: Sites in 5 US cities, Sydney and Auckland.
Source: ClinicalTrials.gov NCT06907875
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- ClinicalTrials.gov. A Phase 1/2 Open-label Dose-escalation Study to Evaluate the Safety, Tolerability, and Biological Activity of EPI-321, an AAVrh74-delivered Epigenetic Editing Therapy in Adult FSHD Patients. https://clinicaltrials.gov/study/NCT06907875
- Epicrispr Biotechnologies, via Business Wire · 2025-04-03. Epicrispr Biotechnologies Announces FDA Clearance of IND Application for EPI-321, A First-in-Class Epigenetic Therapy for FSHD. https://www.businesswire.com/news/home/20250403888509/en/Epicrispr-Biotechnologies-Announces-FDA-Clearance-of-IND-Application-for-EPI-321-A-First-in-Class-Epigenetic-Therapy-for-FSHD
- Epicrispr Biotechnologies, via Business Wire · 2026-01-08. Epicrispr Reports Early Clinical Activity and Favorable Safety Profile in First-in-Human Epigenetic Editing Study for FSHD. https://www.businesswire.com/news/home/20260108594812/en
- Epicrispr Biotechnologies, via BioSpace (Business Wire original dated June 26, 2026) · 2026-06-26. Epicrispr Reports First Clinical Evidence of Increased Lean Muscle Volume in Patients with FSHD Following Treatment with EPI-321. https://www.biospace.com/press-releases/epicrispr-reports-first-clinical-evidence-of-increased-lean-muscle-volume-in-patients-with-fshd-following-treatment-with-epi-321
- Epicrispr Biotechnologies, via BioSpace · 2026-07-07. Epicrispr Completes Enrollment and Dose Escalation in First-in-Human EPI-321 Trial for FSHD. https://www.biospace.com/press-releases/epicrispr-completes-enrollment-and-dose-escalation-in-first-in-human-epi-321-trial-for-fshd
- Epicrispr Biotechnologies · 2026-10-05. Epicrispr Reports Positive Six-Month Data at The World Muscle Society Meeting Demonstrating Increased Lean Muscle Volume and Muscle Strength in FSHD Patients Treated with EPI-321. https://epicrispr.com/epicrispr-reports-positive-six-month-data-at-the-world-muscle-society-meeting-demonstrating-increased-lean-muscle-volume-and-muscle-strength-in-fshd-patients-treated-with-epi-321/
- BioPharma Dive · 2026-08-11. Epicrispr lands $90M to advance epigenetic editing drug for rare muscle disease. https://www.biopharmadive.com/news/epicrispr-series-c-epigenetic-editing-fshd/827340/
- MedlinePlus, National Library of Medicine. Facioscapulohumeral muscular dystrophy: MedlinePlus Genetics. https://medlineplus.gov/genetics/condition/facioscapulohumeral-muscular-dystrophy/
- National Organization for Rare Disorders. Facioscapulohumeral Muscular Dystrophy - Symptoms, Causes, Treatment | NORD. https://rarediseases.org/rare-diseases/facioscapulohumeral-muscular-dystrophy/