uniQure Expanding Clinical Pipeline to Fabry Disease


The IND clearance sets AMT-191 to be evaluated in a clinical trial alongside the company's gene therapies for ALS and Huntington disease.

The FDA has cleared uniQure’s investigational new drug (IND) application to evaluate AMT-191 gene therapy in patients with Fabry disease.1

“The clearance of the IND for AMT-191 represents a key milestone for the company, with four programs now in clinical phase,” Walid Abi-Saab, MD, chief medical officer, uniQure, said in a statement.1 “AMT-191 has the potential to be a differentiated gene therapy for the one-time treatment of Fabry disease, incorporating a proprietary promoter and leveraging our validated AAV5 technology comprised within HEMGENIX®, an approved liver-directed gene therapy for the treatment of hemophilia B developed by uniQure. We have designed the Phase I/II study to provide dose-ranging biomarker data as rapidly and cost-effectively as possible, and we look forward to enrolling our first patient in the first half of 2024.”

AMT-191 is an adeno-associated virus vector (AAV5) gene therapy product that delivers an α-galactosidase A (GLA) transgene targeted to the liver to produce the GLA protein deficient in patients with Fabry disease. The current standard of care treatment for Fabry is enzyme replacement therapy, so AMT-191 represents a potential one-time treatment. uniQure plans to soon initiate a first-in-human Phase 1/2a clinical trial in the United States. The multicenter, open-label trial will consist of 2 dose-escalating cohorts of 3 patients each to assess safety, tolerability, and efficacy of AMT-191 in patients with Fabry disease.

uniQure most recently announced an earlier IND clearance for another of its AAV gene therapies, AMT-260.2 AMT-260 is an mRNA-based gene therapy that is set to be evaluated in patients with refractory mesial temporal lobe epilepsy (MTLE) in a phase 1/2a clinical trial. In accordance with a previous announcement, screening of potential participants should be ongoing.

WATCH NOW: Robert J. Hopkin, MD, on Assessing ST-920 for Fabry Disease

“The clearance of the IND for AMT-260 is an important achievement in advancing our pipeline and is our next program to enter clinical development in an area of high unmet medical need,” Abi-Saab said in an earlier statement.“There are few treatment options for patients who have refractory MTLE, and we are pleased to soon begin the clinical investigation of this 1-time administered gene therapy approach as a potential new treatment.”

AMT-191 is set to join several competitors in the investigational pipeline for Fabry. One such program is Sangamo Therapeutics' isaralgagene civaparvovec (ST-920) which is being evaluated in the phase 1/2 STAAR clinical trial (NCT04046224). The therapy has shown a manageable safety profile so far.3

“We have not had a big inflammatory reaction. In fact, no patients have required prolonged hospitalization, intensive monitoring, or medications to suppress inflammation against either the α-galactosidase A protein that's produced or against the vector that's modified from the AAV viruses. That is actually a huge deal because one of the limiting factors on implementation of gene therapy has been the triggering of the immune system and the [adverse] effects related to that,” investigator Robert J. Hopkin, MD, an associate professor of clinical pediatrics at Cincinnati Children's Hospital Medical Center, told CGTLive.

1. uniQure announces FDA clearance of investigational new drug application for AMT-191 gene therapy for Fabry disease patient enrollment expected to begin in first half of 2024. News release. UniQure. November 29, 2023. https://www.biospace.com/article/releases/uniqure-announces-fda-clearance-of-investigational-new-drug-application-for-amt-191-gene-therapy-for-fabry-diseasepatient-enrollment-expected-to-begin-in-first-half-of-2024/
2. uniQure announces FDA clearance of investigational new drug application for AMT-260 gene therapy for refractory mesial temporal lobe epilepsy. News release. uniQure N.V. September 5, 2023. Accessed September 7, 2023. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-fda-clearance-investigational-new-drug-0
3. Hopkin RJ, Ganash J, Deegan P, et al. STAAR, a phase 1/2 study of isaralgagene civaparvovec (ST-920) gene therapy in adults with Fabry disease. Presented at: WORLDSymposium 2023; February 22-26. Orlando, FL.
Recent Videos
David Dimmock, MBBS, on AI-Guided ASO Development for Ultra-Rare Diseases
Leigh Ramos-Platt, MD, on Looking Forward to Gene Therapy’s Growth
Sowmya Viswanathan, PhD, on Translating Cell Therapies to the Clinic at ISCT 2024
Omer A. Abdul Hamid, MD, on Improving Gene Therapy’s Effect and Accessibility
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Robert J. Hopkin, MD, on Looking Deeper into Fabry Disease Biology
Alessandro Aiuti, MD, PhD, on Durable, Clinically Meaningful Efficacy of Arsa-Cel in Metachromatic Leukodystrophy
Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials
Maria Escolar, MD, the chief medical officer of Forge Biologics
John Murphy, PhD, the chief scientific officer of Arbor Biotechnologies
© 2024 MJH Life Sciences

All rights reserved.