Six of 7 patients reported improvements in dry mouth after treatment with AAV-hAQP1.
The gene therapy AAV-hAQP1 (MeiraGTx) improved symptoms in patients with grade 2/3 radiation-induced xerostomia —or dry mouth— according to data from the phase 1 AQUAx trial (NCT04043104).
“We are very pleased to share this preliminary data from cohorts 1-3 of the AQUAx trial which provides encouraging evidence of the emerging clinical profile of AAV-hAQP1 for the treatment of radiation-induced xerostomia. While the primary endpoint of this Phase 1 trial is safety, we have seen both efficacy and durability in patients treated so far,” Alexandria Forbes, PhD, president and chief executive officer, MeiraGTx, said in a statement.
The open-label, non-randomized, dose escalationAQUAx trial is evaluating the safety of AAV-hQAP1 administered via Stensen's duct to at least 1 parotid gland in patients that previously received radiation treatment for head and neck cancer, have been cancer-free for at least 5 years, and have been diagnosed with grade 2/3 radiation-induced xerostomia. The trial is also evaluating exploratory efficacy as measured by patient-reported outcomes (PROs) of xerostomia symptoms.
The trial has unilaterally dosed 12 patients in 4 cohorts and has added 4 cohorts for bilateral, dose-escalation treatment; 1 new cohort of 3 patients has been dosed. The trial is being conducted across 6 centers in the US and Canada and continues to screen patients. All participants will be followed for 1 year post-treatment as part of the AQUAx trial and for another 4 years in a long-term follow-up study.
Patients reported positive outcomes with AAV-hAQP1 treatment. Most participants (n = 6) followed up with at day 90 reported that their dry mouth was better after treatment, with a clinically meaningful decrease in disease burden of at least 10 points. Three participants scored the change with the highest level of improvement. These changes persisted in the 2 patients who reached a 180-day assessment and 1 participant reported a complete resolution of symptoms at day 360. No participants reported worsening xerostomia symptoms.
“The size of the effects we are seeing at these early stages in the study are clinically meaningful and appear greater than those seen to date with approved drugs for RIX and xerostomia associated with Sjögren’s Syndrome. These results point to the potential for AAV-hAQP1 to be a disease-modifying, one-time treatment for this large population of patients who currently have no effective treatment options for this devastating and intractable condition,” Forbes added.
AAV-hAQP1 has been well tolerated with no serious adverse events (AEs) or dose-limiting toxicities as of December 6, 2021. MeiraGTx plans to initiate a placebo-controlled, randomized, double-blind, phase 2 study to evaluate 2 dose levels of the gene therapy candidate in the second half of 2022. The phase 2 study will evaluate 12-month change from baseline in McMaster Global Rate of Change questionnaire as its primary endpoint, the 12-month change from baseline in Symptom-specific Xerostomia Questionnaire as its secondary endpoint, and whole saliva volume as an exploratory endpoint.