Gene Therapy Proves Positive in Parkinson Disease in Phase 2 Study


Patients treated with Axovant’s gene therapy AXO-Lenti-PD reported improvements of 40% in UPDRS-III scores, and 71% improvement in activities of daily living.

Pavan Cheruvu, MD, chief executive officer, Axovant

Pavan Cheruvu, MD

New data from the phase 2 SUNRISE-PD trial (NCT03720418) suggest that patients with Parkinson disease treated with Axovant Gene Therapies investigational agent AXO-Lenti-PD experienced no treatment-related serious adverse events (AEs) as well as improvements in OFF time from baseline values.

Axovant announced that overall, treated patients experienced a 40% improvement in Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores, equating to a 21-point mean gain, which exceeded the pre-defined criteria for success. These data from the open-label, dose-escalation trial, included the 6 months of follow-up for the second cohort of patients administered 1.4x107 TU of the gene therapy.

“These data, showing over 20 points of improvement on the UPDRS Part III OFF motor function score, as well as meaningful improvements in quality of life measures, underscores the potentially best-in-class profile of AXO-Lenti-PD gene therapy in Parkinson’s disease,” said Gavin Corcoran, MD, chief research and development officer, Axovant, in a statement. “The totality of data seen thus far reinforces my belief that AXO-Lenti-PD has the potential to transform the treatment of patients with Parkinson’s disease through one-time administration of gene therapy.”

This second cohort included 4 patients, who had an average age of 57 years and mean duration of disease of 13 years. Of those patients in Cohort 2, half were available for comparison from their baseline average UPDRS-III score of 52.

Notably, COVID-19 did not allow for 1 of the 4 patients at a UK clinical site to participate in UPDRS assessments and the mandatory washout of background levodopa therapy at the 6-month mark, and another patient refused participation. As such, those values were missing for those 2 patients. Although, 100% of the 4-patient cohort was able to complete the other 6-month efficacy assessments, which included patient-recorded Hauser diaries.

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“We are highly encouraged by the growing evidence of dose-response and apparent clinical improvement observed in the SUNRISE-PD study, combined with a favorable safety profile. These results exceed our pre-defined base case criteria of 10-15 points of improvement from baseline on the UPDRS Part III OFF score and are above a threshold considered clinically meaningful in the medical literature and as compared to standard of care,” Pavan Cheruvu, MD, chief executive officer, Axovant, said in a statement. “Although the COVID-19 pandemic impacted our ability to collect full UPDRS data from the cohort, the safety of our patients and staff is our first priority, and we have begun work on validating new technologies that may enable remote-based clinical assessments at future time points in order to obtain complete data sets.”

Axovant noted that it is collaborating with its sites and the investigators “to ensure safe and ethical data collection at future time-points through the pandemic in accordance with regulatory guidance.”

The improvement in the UPDRS-III OFF scores in Cohort 2 displayed evidence of a dose-response with AXO-Lenti-PD compared to Cohort 1 (n = 2) as well as the low- (n = 3), medium- (n = 6), and high-dose (n = 6) cohorts of ProSavin that were previously evaluated in a separate phase 1/2 study. Additionally, the 2 evaluable patients in Cohort 2 showed a 14-point mean improvement in activities of daily living, as measured by UPDRS part II scores, indicating a 71% increase.

The Hauser diary “good ON time” was defined as the sum of ON time without dyskinesias and ON time with non-troublesome dyskinesias, which at baseline was 10.2 hours. The value was improved by an average of 2.2 hours for all 4 patients. Likewise, diary OFF time, defined as the time when medication has worn off and is no longer providing mobility benefit, was also improved, this time by an average of 2.3 hours for all 4 patients. At baseline, OFF time was 5.8 hours.

“Building on these encouraging results, we expect to begin dosing in EXPLORE-PD, a randomized, sham-controlled study in 2021, and will additionally evaluate the safety and tolerability of higher volumes of infusion,” Corcoran added. Axovant expects that investigation of those outcomes to increase putaminal coverage and decrease time in the operating room.

Corcoran noted that Axovant was looking forward to announcing further data, as well as program updates, at its upcoming Parkinson disease Research and Development Day, planned for October 30, 2020.

Axovant Announces Positive Six-Month Follow-up Data From Second Cohort of Sunrise-PD Phase 2 Trial of Axo-Lenti-PD Gene Therapy. News release. New York, NY. Axovant. Published October 6, 2020. Accessed October 6, 2020.
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