Axovant, a clinical-stage gene therapy company that specifically investigates new treatment options for neuromuscular and neurological conditions, has released promising data from the Phase II SUNRISE-PD study. The study, which started at the end of 2018 and is still underway, is investigating AXO-Lenti-PD, a gene therapy that aims to increase the activity of three genes normally found in the body (aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and cyclohydrolase). The enzymes, or proteins, created by these genes can lead to the synthesis of dopamine.1
The SUNRISE-PD study
The idea behind the treatment is that by delivering these genes into the body and activating them, they can then go on to carry out their normal function, eventually leading to an increase in dopamine creation and delivery to the brain. This may help restore levels of dopamine in the brain and/or decrease changes in dopamine levels that can happen as the result of PD.
Initial study findings
The most significant results found thus far were a 42% (25-point) mean improvement on Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (motor) OFF scores. The UPDRS score measures motor function, and is graded on a scale of 0 to 108, with a lower score indicating better motor-symptom outcomes and improvement. This score is referred to as an OFF score when there are no background medical therapies, like oral levodopa, present, thus painting a clearer picture of what AXO-Lenti-PD may be able to do on its own. At the three-month mark, scores improved by an average of 25-points, with one participant having an improvement score of 36 points, and another participant improving by 14 points. Currently, data have been released from the first AXO-Lenti-PD cohort, which included two participants with advanced PD.
There were also improvements noted in activities of daily living scores and in complications of therapy scores. Specifically, reductions in ON state dyskinesias (involuntary movements) were found in those taking the AXO-Lenti-PD. Dyskinesias were evaluated using the Rush Dyskinesia Rating Scale ON score, which is typically used for individuals taking oral levodopa to determine their functional disability while trying to carry out activities of daily living. In addition to this scale, participants were also asked to keep a diary of their experiences, including the frequency of dyskinesias. As with the improved scale scores, the participant diaries also demonstrated an improvement in diary ON time with dyskinesia. The average reduction of ON time with dyskinesia was 3.5 hours, a 57% improvement from baseline experiences. Overall, for the first cohort of participants, motor symptoms seemed to improve from baseline.
The therapy was not linked to any serious adverse events at this time, and was generally well-tolerated through this stage of study. Dosing of the next cohort of participants will begin before mid-2019. The administration of AXO-Lenti-PD is a one-time dosage at this time. An earlier version of AXO-Lenti-PD, called ProSavin, showed a similar trend when it was tested, however, even at a lower dosage, AXO-Lenti-PD is showing more promising results thus far, and will continue to be investigated.1
Axovant Reports Positive Interim Results from First Cohort of SUNRISE-PD Phase 2 Trial of AXO-Lenti-PD Gene Therapy in Parkinson’s Disease. Axovant Sciences Ltd: Axovant Gene Therapies. http://investors.axovant.com/news-releases/news-release-details/axovant-reports-positive-interim-results-first-cohort-sunrise-pd. Published March 11, 2019. Accessed March 16, 2019.