The landscape of lysosomal disorder treatments underwent significant shifts in 2024, characterized by both promising advances and notable setbacks in gene therapy development. These developments have important implications for patients affected by these rare genetic conditions.
Significant Pipeline Changes in Pompe Disease Treatment
In a major development, Roche discontinued its gene therapy program SPK-3006 for late-onset Pompe disease, halting the phase 1/2 RESOLUTE trial. This decision came as part of the portfolio evaluation following Roche's acquisition of Spark Therapeutics in 2019.
However, the field saw new hope with AskBio's advancement of ACTUS-101, an adeno-associated virus (AAV) gene therapy targeting acid-alpha-glucosidase (GAA) deficiency. According to Sheila Mikhail, JD, "ACTUS-101 could replace enzyme replacement therapy (ERT) every other week with the potential to be a groundbreaking metabolic treatment for an unforgiving disease."
Breakthrough Progress in Fabry Disease Treatment
Sangamo Therapeutics achieved a significant milestone in their Fabry disease program. The FDA provided support for an abbreviated pathway to approval for ST-920 (isaralgagene civaparvovec), requiring data from just 25 patients without a control arm. Dr. Nathalie Dubois Stringfellow highlighted the significance: "The US and European regulatory support for ST-920 and the serious unmet medical need in Fabry disease signal the important role that ST-920 could play in improving the lives of Fabry patients across the globe."
Mixed Results in Other Rare Disease Programs
The year also saw disappointing results in GM1 gangliosidosis treatment. The LYS-GM101 gene therapy trial was discontinued by Lysogene after showing limited efficacy. Dr. Arunabha Ghosh reported that despite acceptable safety profiles, there was "little evidence for potential efficacy of the therapy, with limited biochemical correction, and clear clinical decline in all participants."
Promising Developments in MPS IIIA Treatment
More encouragingly, Orchard Therapeutics' OTL-201, a genetically-modified hematopoietic stem cell therapy for mucopolysaccharidosis type IIIA (MPS IIIA), showed promising results. Dr. Simon Jones reported significant reductions in heparan sulphate levels across plasma, urine, and cerebrospinal fluid, with early neurocognitive data suggesting potential modification of the neurological phenotype.
The therapy demonstrated "robust, prompt, sustained, multilineage engraftment of genetically modified cells," according to trial results presented at the 2024 WORLD Symposium. Four out of five patients showed progression on the Kaufman instrument, indicating potential neurological benefits.
