MeiraGTx Holdings plc announced positive clinical data from the completed Phase 1 AQUAx study of AAV2-hAQP1 for the treatment of grade 2/3 radiation-induced xerostomia (RIX). Phase 1 AQUAx Trial of AAV2-hAPQ1 for the Treatment of Grade 2/3 Radiation-Induced Xerostomia: AQUAx is an open label, multi-center, dose escalation study of a single administration of AAV2-hAQP1 to one or both parotid glands in participants with radiation-induced salivary hypofunction and grade 2/3 xerostomia. There were 4 escalating dose cohorts with 3 participants per cohort for both unilaterallly and bilaterally treated participants.

All participants were followed for 1-year post-treatment in the Phase 1 AQUAx study and were then enrolled in a long-term follow-up study for a total of 5 years. The primary endpoint was safety and the secondary endpoints included change from baseline to 12 months in patient-reported measures of xerostomia symptoms using the Global Rate of Change Questionnaire, or GRCQ, and the Xerostomia Questionnaire, or XQ. In addition, whole saliva flow rate was assessed.

The study was conducted at 4 centers, with 3 in the US and 1 in Canada. Treatment appears safe and well tolerated at each dose tested with no dose-limiting toxicity or treatment-related serious adverse events. Efficacy Data presented from the24 participants treated in the AQUAx study: Improvements observed in both of the patient reported assessments of xerostomia symptoms, Global Rate of Change Questionnaire (GRCQ) and Xerostomia Questionnaire (XQ), in both unilateral and bilateral treated cohorts at 12 months post-treatment; Improvements in salivary flow were seen in unilateral as well as bilateral cohorts; Early long-term follow-up data suggest durability of improvement out to at least 3 years post-treatment.

McMaster Global Rate of Change Questionnaire (GRCQ): Bilateral Cohorts (n=12) to 12 Months: 10/12 (83%) participants at 12 months reported symptoms of dry mouth as ”better” following treatment; Each of these 10 participants rated changes in xerostomia scores that were “important” or “very important” with a score of 2 or more at 12 months; 5 participants rated the change in xerostomia symptoms with the highest improvement scores of 6 or 7 denoting a “very important improvement”; No participant reported worsening of xerostomia symptoms. Unilateral Cohorts (n=12) to 12 Months: 8/12 participants at 12 months reported symptoms of dry mouth as “better” following treatment; Each of these 8 participants rated changes in xerostomia scores that were “important” or “very important” with a score of 2 or more at 12 months; 4 of these participants rated the change in xerostomia symptoms with the highest improvement scores of 6 or 7 denoting “a very important improvement”; Improvement in xerostomia symptoms persisted through 2 years in 4 participants and 3 years in 3 participants who reached these timepoints; No participant reported worsening of xerostomia symptoms. Combined Unilateral and Bilateral Cohorts: Overall, the average improvement in GRCQ score was greater in bilaterally treated participants compared to those treated unilaterally; Improvements were maintained and increased over time in both unilateral and bilateral cohorts; A 2-point change in GRCQ is considered important by patients; Changes of 3 points or greater are considered a substantial improvement over standard of care and “transformative” by KOLs; Unilaterally treated cohorts achieved overall improvement of >3 points at 12 months; Bilaterally treated cohorts achieved overall improvement of >3 points at 2 months and an overall improvement of 4 points by 6 months, with this 4-point improvement maintained at 12 months.