Atamyo Therapeutics’ phase 1/2 ATA-001-FKRP clinical trial (EudraCT 2021-004276-33, NCT05224505) for ATA-100 (previously referred to as GNT0006), an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat fukutin-related protein (FKRP) limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), has been cleared by its data safety monitoring board (DSMB) to begin enrolling patients in its second cohort based on initial positive results from the first cohort.1 The company announced the results at the 30th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), held October 24-27 in Brussels, Belgium.
“The preliminary results from cohort 1 with the first dose tested already show encouraging results from a safety and efficacy perspective,” principal investigator John Vissing, MD, DMSci, a professor of Neurology at the University of Copenhagen, Denmark, and the director of the Copenhagen Neuromuscular Center at the National Hospital, Rigshospitalet, said in a statement.1 “ATA-100 treatment has a life-changing potential in an indication where there is no approved treatment.”
Atamyo reported that the first 3 patients who were treated with the gene therapy in ATA-001 each experienced a “marked” decline in creatine kinase levels. Furthermore, the company noted that improved velocity, which was maintained a year after treatment, the vanishing of symptoms including cramps and myalgia, and improved quality of life were observed among the treated patients. A 3-month muscle biopsy additionally indicated transgene expression and showed corrected centronucleation.
Biological safety and tolerability were reported to be good and there were no unexpected safety signals observed. The DSMB has cleared Atamyo to go forward with a planned dose for the second cohort that is 3 times higher than the dose used for the first cohort.
- Atamyo Therapeutics' phase 1/2 clinical trial for ATA-100, an investigational gene therapy for fukutin-related protein (FKRP) limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), has received clearance from its data safety monitoring board (DSMB) to enroll patients in its second cohort based on positive results from the first cohort.
- Preliminary results from the first cohort showed encouraging safety and efficacy results, including a decline in creatine kinase levels, improved velocity, vanishing of symptoms, improved quality of life, and transgene expression in muscle fibers.
- ATA-100, administered as a single dose, is designed to deliver a functional copy of the FKRP gene. It has received orphan drug designation from the FDA and the European Medicines Agency.
“These first results, in particular those related to transgene expression in muscle fibers are really exciting,” Sophie Olivier, MD, the chief medical officer of Atamyo, said in a statement.1 “With the DSMB clearance to start the 2nd cohort, we are looking forward to enrolling new patients in Europe and in the US.”
ATA-100, which is administered as a single dose, is intended to deliver a functional copy of FKRP, the disease-targeted gene. It was announced in February 2022 that ATA-100 had received orphan drug designation from the FDA for the treatment of LGMD/R9 and from the European Medicines Agency for the treatment of LGMD.2 The multicenter ATA-001 trial is being conducted in Denmark, France, and the United Kingdom under clinical trial applications (CTAs) cleared between 2021 and 2022.3-5 The company announced the dosing of the first patient in the study in September 2022.6 More recently, in September 2023, Atamyo received clearance of an investigational new drug (IND) application with which the company intends to expand the clinical trial activities to the United States.7
Atamyo is also developing ATA-200, an investigational AAV vector-based gene therapy, for the treatment of γ-sarcoglycan (SGCG)-related limb-girdle muscular dystrophy Type 2C/R5.8 The company submitted a CTA for ATA-200 in September 2023. Pending clearance of the CTA, the company is planning to evaluate the gene therapy in a multicenter, dose-escalation phase 1b clinical trial (EUCT 2023-506440-16-00), with dosing of patients expected to begin in the first half of 2024. At the same time submission of the CTA was announced, Atamyo also noted that it had received $8.6 million in nondilutive financing from France 2030, a program operated by Bpifrance, for ATA-200's development.
1. Girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), presented at ESGCT. News release. Atamyo Therapeutics. October 27, 2023. Accessed November 1, 2023. https://atamyo.com/press-releases/first-clinical-results-of-ata-100-a-gene-therapy-for-the-treatment-of-limb-girdle-muscular-dystrophy-type-2i-r9-lgmd2i-r9-presented-at-esgct/
2. Atamyo Therapeutics reaches significant regulatory and financial milestones for ATA-100, its gene therapy to treat limb-girdle muscular dystrophy type 2I/R9. News Release. Atamyo Therapeutics. February 24, 2022. Accessed November 1, 2023. https://atamyo.com/press-releases/atamyo-therapeutics-reaches-significant-regulatory-and-financial-milestones-for-ata-100-its-gene-therapy-to-treat-limb-girdle-muscular-dystrophy-type-2i-r9/
3. Atamyo Therapeutics obtains first regulatory authorization in Europe to initiate a clinical trial for ATA-100, its gene therapy to treat limb-girdle muscular dystrophy type 2I/R9. News release. Atamyo Therapeutics. December 6, 2021. Accessed November 1, 2023. https://atamyo.com/press-releases/2021/atamyo-therapeutics-obtains-first-regulatory-authorization-in-europe-to-initiate-a-clinical-trial-for-ata-100-its-gene-therapy-to-treat-limb-girdle-muscular-dystrophy-type-2i-r9/
4. Atamyo Therapeutics reaches significant regulatory and financial milestones for ATA-100, its gene therapy to treat limb-girdle muscular dystrophy type 2I/R9. News Release. Atamyo Therapeutics. February 24, 2022. Accessed November 1, 2023. https://atamyo.com/press-releases/atamyo-therapeutics-reaches-significant-regulatory-and-financial-milestones-for-ata-100-its-gene-therapy-to-treat-limb-girdle-muscular-dystrophy-type-2i-r9/
5. Atamyo Therapeutics announces significant milestones for ATA-100 and ATA-200, its gene therapy programs to treat limb-girdle muscular dystrophy 2I/R9 and 2C/R5. News release. Atamyo Therapeutics. May16, 2022. Accessed November 1, 2023. https://atamyo.com/press-releases/atamyo-therapeutics-announces-significant-milestones-for-ata-100-and-ata-200-its-gene-therapy-programs-to-treat-limb-girdle-muscular-dystrophy-2i-r9-and-2c-r5/
6. Atamyo Therapeutics announces first patient dosed with ATA-100 gene therapy in LGMD-R9 clinical trial. News Release. Atamyo Therapeutics. September 26, 2022. Accessed November 1, 2023. https://atamyo.com/press-releases/atamyo-therapeutics-announces-first-patient-dosed-with-ata-100-gene-therapy-in-lgmd-r9-clinical-trial/
7. IND for ATA-100, a gene therapy for the treatment of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), cleared to proceed by FDA. News release. Atamyo Therapeutics. September 5, 2023. Accessed November 1, 2023. https://atamyo.com/press-releases/2023/ind-for-ata-100-a-gene-therapy-for-the-treatment-of-limb-girdle-muscular-dystrophy-type-2i-r9-lgmd2i-r9-cleared-to-proceed-by-fda/
8. ATA-200, AtamyoTherapeutics’ gene therapy to treat limb-girdle muscular dystrophy type 2C/R5, reaches key milestones with the filing of a clinical trial application in Europe and a non-dilutive financing from France 2030 program. News release. AtamyoTherapeutics. September 19, 2023. Accessed November 1, 2023. https://atamyo.com/press-releases/https-atamyo-com-wp-content-uploads-pr-sept-19-2023-ata-200-reaches-key-milestones-with-cta-in-europe-and-france2030-financing-pdf/