MeiraGTx Holdings plc (Nasdaq: MGTX) has announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to AAV2-hAQP1 for the treatment of Grade 2/3 radiation-induced xerostomia (RIX). This designation aims to expedite the development and review of this promising gene therapy for a condition with limited treatment options.
Clinical Significance of RMAT Designation
The RMAT designation, established under the 21st Century Cures Act, is reserved for regenerative medicine therapies that address serious or life-threatening diseases. It includes benefits similar to Breakthrough Therapy designation, such as increased interaction with the FDA, rolling review, and potential Priority Review of a product’s biologics license application (BLA). According to MeiraGTx, less than half of all RMAT designation applications are granted, highlighting the rigor of the selection process and the potential significance of AAV2-hAQP1.
AAV2-hAQP1: A Novel Gene Therapy for Xerostomia
AAV2-hAQP1 is an investigational gene therapy designed to alleviate the symptoms of radiation-induced xerostomia, a common and debilitating side effect of radiation treatment for head and neck cancer. Approximately 30-40% of patients treated with radiation for head and neck cancer develop Grade 2/3 RIX, characterized by severe dry mouth due to damaged salivary glands. Currently, there are no effective treatments for this condition, leaving a significant unmet need.
Promising Phase 1 Data
Data from MeiraGTx’s Phase 1 AQUAx clinical trial, presented at the American Academy of Oral Medicine (AAOM) 2024 annual meeting, demonstrated that AAV2-hAQP1 treatment resulted in significant improvements across three different patient-reported outcomes and in saliva production. Notably, the trial reported no treatment-related serious adverse events or dose-limiting toxicities. These positive results underpinned the FDA’s decision to grant RMAT designation.
Ongoing Phase 2 Trial
The Phase 2 AQUAx2 trial (NCT05926765) is currently enrolling participants at multiple sites in the U.S., Canada, and the U.K. This randomized, double-blind, placebo-controlled study is designed to further evaluate the efficacy and safety of AAV2-hAQP1. MeiraGTx has reached an agreement with the FDA that the Phase 2 trial can serve as a pivotal study to support a potential BLA filing, contingent on the use of material manufactured using MeiraGTx’s proprietary production process and in-house manufacturing facilities.
Addressing an Unmet Need
According to MeiraGTx, there are over 170,000 patients in the U.S. currently suffering from Grade 2/3 RIX, with an additional 15,000 new patients diagnosed each year. AAV2-hAQP1 involves a small dose locally delivered to the salivary gland via a non-invasive procedure, potentially offering a cost-effective and durable solution for this large patient population. Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx, stated that the company looks forward to working closely with the FDA to bring this potential life-changing therapy to patients with no alternative treatments as quickly as possible.
