Development Halted on Gene Therapy Candidate AXO-Lenti-PD

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by Steve Bryson, PhD |

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Sio Gene Therapies (Sio), formerly known as Axovant, intends to stop  development of AXO-Lenti-PD, an investigational gene therapy for Parkinson’s disease.

Sio will return the global rights to develop and market the therapy to Oxford Biomedica, which licensed the treatment to Sio in 2018.

The announcement comes on the heels of the resignation of Sio’s CEO and the deprioritization of the program due to constraints on resources needed to advance the therapy.

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Although Oxford Biomedica has no plans to continue developing AXO-Lenti-PD, they will out-license it again to a suitable partner with sufficient resources and funding for further development, the company indicated in a press release.

AXO-Lenti-PD uses a modified, harmless virus to deliver three genes that provide instructions to make key enzymes that generate dopamine. Dopamine is the nerve cell-signaling molecule, or neurotransmitter, produced at low levels in Parkinson’s patients. The investigational therapy is designed to provide sustained dopamine levels after a single administration.

Oxford initially completed a Phase 1/2 trial of ProSavin (NCT00627588), a predecessor of AXO-Lenti-PD, which was well-tolerated and significantly improved motor function at six and 12 months in Parkinson’s patients. These benefits were sustained for up to four years in most participants.

In subsequent preclinical animal studies, AXO-Lenti-PD demonstrated increased production of the key enzymes and fivefold greater potency in improving movement and behavior compared to ProSavin.

After Oxford licensed the therapy, previously called OXB-102, Sio sponsored SUNRISE-PD, an ongoing Phase 1/2 clinical trial (NCT03720418) evaluating AXO-Lenti-PD in adult Parkinson’s patients. Part A of the trial investigated appropriate doses for Part B, in which patients were assigned randomly to AXO-Lenti-PD or a sham procedure to serve as controls.

Two participants were first treated at a low dose, which, after one year, demonstrated a good safety profile and eased motor symptoms during “off” periods when Parkinson’s medications do not effectively control symptoms. Better scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II “Off” score, which assessed the activities of daily life, also were reported.

A second group of four participants, given an intermediate dose, also showed a good safety profile with no serious treatment-related adverse events reported after six months. Among the two patients with available UPDRS Part II “Off” data, which assessed motor function, mean scores dropped by 21 points — a 40% improvement in motor function compared to pre-treatment.

According to Oxford Biomedica, it will continue to focus on developing and manufacturing gene and cell therapies as a contract research organization.

“Oxford Biomedica’s goal is to become an innovative global viral vector leader that provides solutions to cell and gene therapy for their process development and manufacturing needs across key viral vectors,” said Roch Doliveux, PhD, chair and interim CEO of Oxford Biomedica. “The Parkinson’s programme is non-core to our strategy.”