Objective: Results from cohort 2 in the Phase 1/2 SUNRISE-PD study (NCT03720418) at 6 months (6M) post administration of AXO-Lenti-PD (ALPD) gene therapy are presented.

Background: ALPD, previously known as OXB-102, uses a lentiviral vector that includes the three genes required for endogenous dopamine synthesis (TH, CH1 and AADC) and is delivered via one-time direct bilateral infusions into each putamen. In cohort 1, where two subjects received low dose (4.2E+6 Transducing Units [TU]), ALPD was well tolerated and supported dose escalation to cohort 2.

Method: In cohort 2, four subjects were dosed with ALPD mid dose (1.4E+7 TU). Subjects used the Hauser diary for up to 3 consecutive days within the week prior to the baseline (BL) and 6M visits to log their motor function (either Asleep, ON without dyskinesia, ON with non-troublesome dyskinesia, ON with troublesome dyskinesia, or OFF) at 30 minute intervals normalized to 16 waking hours. Levodopa equivalent daily dose (LEDD) was calculated. UPDRS was assessed on site, and due to COVID-19 and a subject refusal, two subjects did not have 6M UPDRS OFF data.

Results: At 6M, for the four cohort 2 subjects, there was a mean increase from BL in good ON time (ON without dyskinesia plus ON with non-troublesome dyskinesia) of 2.2 hours and a mean decrease from BL in OFF time of 2.3 hours. Mean LEDD decreased by 271.0 mg, 13% lower than at BL. For the two UPDRS-evaluable subjects, individual improvements were by 12 and 15 points from BL in UPDRS Part II (Activities of Daily Living) OFF, and by 22 and 19 points from BL in UPDRS Part III (Motor Examination) OFF, respectively. One subject had two serious adverse events of confusional state and wound infection which resolved and were unrelated to ALPD and possibly related to the surgical procedure. No hypersensitivity, immune response or endotoxicity related adverse events and no serious unexpected suspected adverse reactions were reported. No subject died or discontinued from the study.

Conclusion: Initial data of AXO-Lenti-PD gene therapy at 6M from cohort 2 in the SUNRISE-PD trial demonstrate that ALPD was generally well tolerated and suggest the potential for a clinically relevant effect. Further evaluation of ALPD is planned using a higher dose/volume open label cohort followed by a sham-controlled study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phase-1-2-open-label-dose-evaluation-study-of-axo-lenti-pd-gene-therapy-for-parkinsons-disease-efficacy-safety-and-tolerability-data-from-the-second-cohort-at-6-months/