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.2 “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.
