Atamyo Therapeutics’ Limb-Girdle Muscular Dystrophy Gene Therapy ATA-100 Gets FDA IND Clearance

Atamyo Therapeutics’ 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 received clearance of its investigational new drug (IND) application from the FDA.^1,2

ATA-100, which is administered as a single dose, is intended to deliver a functional copy of the human FKRP gene. ATA-100 is currently being evaluated in a multicenter phase 1/2 clinical trial (EudraCT 2021-004276-33, NCT05224505) in Denmark, France, and the United Kingdom under clinical trial applications (CTAs) that were cleared in each of those countries between 2021 and 2022.^3-5 The company announced the dosing of the first patient in the study in September 2022.² In light of the IND clearance, Atamyo plans to expand the clinical trial activities to the United States.¹

“This IND clearance in an important step to bring ATA-100 to US patients suffering from this highly debilitating LGMD-R9 disease,” Sophie Olivier, MD, the chief medical officer of Atamyo, said in a statement.¹ “After the initiation in 2022 of a phase 1b/2b in Europe, we are looking forward to opening US centers in the near future for this clinical trial.”

It was previously announced in February 2022 that ATA-100 had received orphan drug designation (ODD) from the FDA for the treatment of LGMD/R9 and from the European Medicines Agency for the treatment of LGMD.⁴ At the time, while the CTA in France was still under review, Atamyo also announced that it had received nondilutive public financing in the form of 2 million euros from Bpifrance, as part of the French government’s Deeptech Development Aid program, to support the first in-human trial.

“As LGMD2I/R9 is a disease with no approved treatment, the lives of patients are heavily affected,” Kathryn Bryant, MS, the founder of the Speak Foundation, an association for patients with LGMD, said in a statement issued to CGTLive™. “As an illustration, LGMD2I/R9 patients progressively lose the ability to walk and they are also subject to progressive impairment of their respiratory function. It is exciting to see with this IND clearance that clinical trials are being approved in the US in this indication, which allows patients getting access to potentially life-changing treatments through clinical trials.”

“As a physician following many patients with muscle diseases, it is great to be able provide hope to patients affected by a debilitating disease like LGMDR9, with the introduction of a disease-specific gene therapy developed by Atamyo,” John Vissing, MD, DMSci, the principal investigator of the trial, a professor of Neurology at the University of Copenhagen, Denmark, and the director of the Copenhagen Neuromuscular Center at the National Hospital, Rigshospitalet, added in a statement issued to CGTLive.

ATA-100 is not the only gene therapy in development for the treatment of LGMD2I/R9. Asklepios BioPharmaceutical (AskBio)’s AB-1003 (LION-101), also an AAV vector-based gene therapy, is currently being evaluated in the phase 1/2 LION-CS101 clinical trial (NCT05230459).⁶ ATA-100 is likewise intended to deliver a functional copy of the FKRP gene in a single dose. In August 2023, AskBio announced that the first patient in LION-CS101 had been dosed. AB-1003 received ODD from the European Commission in March 2023 through AskBio’s Europe-based subsidiary, BrainVectis.⁷ Earlier, in June 2021 it was granted fast track designation by the FDA.⁸

“While the inherited nature of LGMD means those with the FKRP gene mutation can’t produce a normal FKRP protein for physiological muscle function, AB-1003 is designed to introduce the normal FKRP gene into the muscle and express a normal protein, and it has shown promise in restoring normal FKRP protein function in muscle in preclinical studies performed in mouse models of LGMD,” Nicholas Johnson, MD, LION-CS101’s principal investigator and vice chair of research in the Department of Neurology at Virginia Commonwealth University School of Medicine, said in an August 2023 statement.⁶ “This trial is the first step toward evaluating the safety of AB-1003 and assessing the potential that AB-1003 has to improve the lives of patients with this serious, inherited ultra rare condition.”

REFERENCES
1. 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 September 7, 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/
2. Atamyo Therapeutics announces first patient dosed with ATA-100 gene therapy in LGMD-R9 clinical trial. News Release. Atamyo Therapeutics. September 26, 2022. https://atamyo.com/press-releases/atamyo-therapeutics-announces-first-patient-dosed-with-ata-100-gene-therapy-in-lgmd-r9-clinical-trial/
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 September 7, 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 September 7, 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 September 7, 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. AskBio announces first patient dosed in phase 1 / phase 2 trial of AB-1003 gene therapy for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). News release. Asklepios BioPharmaceutical, Inc. August 3, 2023. Accessed September 7, 2023. https://www.askbio.com/askbio-announces-first-patient-dosed-in-phase-1-phase-2-lgmd2i-r9/
7. AskBio receives European Commission orphan drug designation through its EU-based subsidiary BrainVectis for AB-1003, a novel investigational AAV gene therapy for the treatment of limb-girdle muscular dystrophy (LGMD). News release. Asklepios BioPharmaceutical, Inc. February 16, 2023. Accessed September 7, 2023. https://www.askbio.com/askbio-receives-european-commission-orphan-drug-designation-through-its-eu-based-subsidiary-brainvectis-for-ab-1003-a-novel-investigational-aav-gene-therapy-for-the-treatment-of-limb-girdle-muscular/
8. AskBio receives FDA fast track designation for LION-101, a novel investigational AAV gene therapy for the treatment of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). News release. Asklepios BioPharmaceutical, Inc. June 28, 2021. Accessed September 7, 2023. https://www.askbio.com/askbio-receives-fda-fast-track-designation-for-lion-101-a-novel-investigational-aav-gene-therapy-for-the-treatment-of-limb-girdle-muscular-dystrophy-type-2i-r9-lgmd2i-r9/