Lysogene Gene Therapies Show Promise in GM1 Gangliosidosis and MPSIIIA


Updated data were presented on LYS-SAF302 and LYS-GM101 at WORLDSymposium.

Lysogene’s gene therapies, which includeLYS-SAF302 for the potential treatment of mucopolysaccharidosis type 3A (MPSIIIA) and LYS-GM101 for the potential treatment of GM1 gangliosidosis, have continued to show safety and efficacy in their respective indications.1,2

Lysogene presented data on both programs at the 18th Annual WORLDSymposium, February 7-11, 2022 in San Diego, California. Lysogene’s chief scientific officer, Ralph Laufer, PhD, presented biomarker data on LYS-SAF302 and Karen PignetAiach, founder, chair, and chief executive officer of Lysogene presented safety data on LYS-GM101.

“Lysogene is developing an AAVrh10 vector for intraparenchymal gene therapy of this disease that contains the SGSH cDNA... the clinical development program consisted of a phase 1 trial (NCT01474343) that was conducted several years ago with a first-generation product called LYS-SAF301 that was conducted in 4 patients demonstrating safety and tolerability, the P3 study (NCT02746341), which was a prospective, non-interventional natural history study, and AAVance (NCT03612869), which is a phase 2/3 open-label clinical trial with our second-generation therapy LYS-SAF302 and its sister video study called PROVIDE,” Laufer said during his presentation.1

The AAVance study has treated 19 patients with intraparenchymal injection of the gene therapy. As previously disclosed, white matter abnormalities associated with treatment have been observed near the injection sites and stabilized and improved from 12 months onwards with no clinically significant, directly attributable symptoms. The program remains on hold due to these changes but is minimally affected since 19 of 20 planned patients were already enrolled and treated. One patient has died 18 months after treatment, but this was deemed unrelated to LYS-SAF302 treatment.

WATCH NOW: Gene Therapy for GM1 Gangliosidosis: Latest Updates

Cerebrospinal fluid reductions of heparin sulfate and GM2/3 ganglioside were observed. The reductions are promising as these enzymes are thought to contribute to neuronal damage in MPSIIIA. Laufer discussed how axonal damage biomarkers did increase from baseline to 6 months, possibly reflecting local damage induced by intracranial administration or disease progression but declined after 6 months, reaching baseline levels at 12 months and levels below baseline from 18 months onwards.

Aiach presented updated safety data on LYS-GM101 which showed that the therapy was well tolerated with no adverse events (AEs) related to the therapy or intraparenchymal administration in the first 2 participants dosed with 2.0 x 1012 vg/mL. Based on these data, 2 additional participants are set to be treated with the therapy in early 2022, completing the firstsafety cohort part of the study.

Safety cohort data will be reviewed by the data safety monitoring board once available for all 4 patients in order to start making plans for the phase 2 part of the study, which expects to enroll at least 12 more participants. Efficacy data will be compared to published historical natural history data with matched assessment tools as well as to ongoing natural history studies and registries.

“There is no disease-modifying therapy currently available for GM1 gangliosidosis. Effective treatment is expected to be achieved by delivery of active β-gal protein to the CNS including the spinal cord, where the major pathology is observed,” Aiach said during her presentation.2

1. Laufer R, Drevot P, Hocquemiller M, et al. AAVance gene therapy study in children with mucopolysaccharidosis type IIIA. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022, San Diego, CA.
2. Frapaise FX, Aiach K. A study of intracisternal administration of adeno-associated viral vector serotype rh.10 carrying the human β-galactosidase cDNA for the treatment of GM1 gangliosidosis: Preliminary results of the safety cohort. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022, San Diego, CA.
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