A single dose of Axovant’s gene therapy candidate AXO-Lenti-PD continues to improve motor function and has been well-tolerated after six months in two patients with advanced Parkinson’s disease, according to early results of an ongoing Phase 1/2 clinical trial.
“We continue to be encouraged by the consistency of the data and improvements in quality of life seen at six months in the two low-dose cohort patients, as we enroll additional patients in the second cohort of the SUNRISE-PD study,” Gavin Corcoran, chief research and development officer at Axovant, said in a press release.
Patient enrollment is ongoing for up to 30 participants, ages 48–70, who have been diagnosed with idiopathic (of unknown cause) Parkinson’s for at least five years. More information on contacts and trial locations (in Europe) is available here.
AXO-Lenti-PD is a gene therapy that uses a harmless virus-based system to deliver three genes that generate three enzymes — tyrosine hydroxylase, cyclohydrolase 1, and aromatic L-amino acid decarboxylase for the production of dopamine, the brain-signaling molecule that is present in low levels in Parkinson’s patients.
The therapy is administrated surgically directly into the brain to restore dopamine levels and provide long-lasting benefits with a single administration.
“Our patient-focused goal of improving motor function, reducing dyskinesia, lowering the requirement for oral levodopa, and improving quality of life is made possible by the continuous dopamine replacement strategy of AXO-Lenti-PD gene therapy,” Corcoran said.
The SUNRISE-PD (NCT03720418) study consists of two parts. Part A is an open-label, dose-escalation phase in which patients receive one of approximately three escalating doses of the gene therapy. In part B of SUNRISE-PD, patients are then randomized to receive either the selected dose from part A or an imitation surgical procedure (control group). The goal is to test the safety, tolerability, and effectiveness of the potential treatment.
The first two patients enrolled received the lowest dose (4.2×106 transducing units) of AXO-Lenti-PD. In March, Axovant revealed results of three months of follow-up.
Now, at six months of follow-up, the patients experienced an average improvement of 17 points in motor function, as measured using the physician-rated Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, which represents an average 29% change from the beginning of the study.
The patients also showed an average improvement of about 20 points from baseline on the UPDRS Part II (activities of daily living) off score, and an average improvement of 3 points from baseline on the UPDRS Part IV (dealing with complications of therapy) off score. “Off time” is when medication — namely levodopa — is not working optimally, and Parkinson’s motor and non-motor symptoms return.
Treatment with AXO-Lenti-PD also was associated with an average reduction of 21% in levodopa equivalent daily dose — the amount of levodopa with a similar effect as the medication taken — at six months.
Data also revealed a mean 18% improvement in dyskinesia — involuntary, jerky movements — at six months, determined with the Rush Dyskinesia Rating Scale “on time” score, which measures functional disability during activities of daily living while on treatment with levodopa.
According to a patient-recorded diary, both patients experienced an improvement in on time without dyskinesia of 2.7 hours, a reduction in on time with non-troublesome dyskinesias of 2.4 hours, a reduction of on time with troublesome dyskinesia of 1.5 hours, and an increase in off time of 0.9 hours.
In addition, the patients reported significant improvements in their quality of life, achieving a reduction of 32 points (65% improvement) from baseline in the Parkinson’s Disease Questionnaire-39 Summary Index score.
“These data at six months highlight the potential for a clinically meaningful improvement over the currently available standard of care for those patients with moderate to advanced Parkinson’s disease,” Corcoran said.
Three-month data from SUNDRISE-PD patients treated with the second dose of AXO-Lenti-PD is expected to be announced during the fourth quarter of this year.