Four Patients Given Higher AXO-Lenti-PD Dose in Gene Therapy Trial

David Melamed, PhD avatar

by David Melamed, PhD |

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IkT-148009 trial

A Phase 1/2 clinical trial testing AXO-Lenti-PD (OXB102), Axovant‘s experimental gene therapy for Parkinson’s disease, has completed dosing of all four adults in a second group in its dose-escalation part of the study.

Six-month data on these patients is expected by year’s end.

AXO-Lenti-PD is a one-time gene therapy that works by delivering three genes involved in the production of dopamine directly to the brain. Dopamine is a neurotransmitter, or a chemical messenger, that is produced by specialized neurons that are gradually lost as a consequence of Parkinson’s disease.

The gene therapy is administered surgically into the brain, and uses a harmless lentivirus that can “infect” brain cells and introduce these genes, potentially leading to a long-lasting production of dopamine.

The trial, called SUNRISE-PD (NCT03720418), expects to enroll up to 30 patients, ages 48–70, at sites in France and the U.K. It is divided into two parts. Part A is dose escalation, in which patients receive one of three consecutively higher doses to determine the gene therapy’s  most effective dose. Part B will randomize patients to either the selected dose from part A or to a sham procedure to serve a control group.

These four people were given an intermediate dose (1.4 x 107 transducing units) of AXO-Lenti-PD; the first two-person group received the lowest dose (4.2×106 transducing units).

Early three- and six-month data on that first group was reported to be encouraging, with AXO-Lenti-PD  being both well tolerated and patients showing better motor function.

One year after receiving the gene therapy, these patients continued to show gains,  including a 37% improvement in off-period motor symptoms (periods when anti-parkinsonian medication wears off) and a better quality-of-life.

These two patients also had a 22-point positive change from baseline (study start) on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II “Off” score, which assesses daily life activities. This improvement was higher than what was observed with ProSavin, another Parkinson’s gene therapy treatment candidate that Axovant evaluated in a separate Phase 1/2 study (NCT01856439).

“Over the last year, Axovant has progressed toward becoming a leading gene therapy company focused on delivering transformative benefit to patients with neurological diseases, while extending the reach of gene therapies to highly prevalent populations such as Parkinson’s disease,” Pavan Cheruvu, MD, CEO of Axovant, in the release.

“We are encouraged by early findings across our programs, which now include evidence of durable motor improvement following administration of AXO-Lenti-PD in Parkinson’s disease,” Cheruvu added.

Axovant also announced that manufacturing of AXO-Lenti-PD doses will be completed by the end of the year, and that it expects to enroll a first patient in Part B of SUNRISE-PD by early next year.

The company is also advancing possible gene therapies for other diseases, including AXO-AAV-GM1 for GM1 gangliosidosis and AXO-AAV-GM2 for Tay-Sachs and Sandhoff disease.