The U.S. Food and Drug Administration (FDA) has cleared MavriX Bio's Investigational New Drug (IND) application for MVX-220, a gene therapy targeting Angelman syndrome (AS), the company announced today. This regulatory milestone enables MavriX Bio to initiate the "ASCEND-AS" first-in-human clinical study, with patient dosing expected to begin in the second half of 2025.
MVX-220 is an investigational adeno-associated virus (AAV) gene therapy designed to address the root cause of Angelman syndrome by restoring functional expression of the UBE3A gene in neurons. The therapy will be administered via a single intra-cisterna magna (ICM) injection.
"We are thrilled to achieve this critical milestone and move one step closer to delivering the first gene therapy to individuals living with Angelman syndrome," said Allyson Berent, DVM, DACVIM, Chief Development Officer of MavriX Bio. "The clearance of our IND signals a key transition point for our development program and our unwavering commitment to advance novel therapeutic options and a potential single treatment therapy for the Angelman community."
Understanding Angelman Syndrome
Angelman syndrome is a rare, non-degenerative neurological disorder affecting approximately 1 in 12,000 to 1 in 20,000 individuals. The condition is characterized by severe developmental delays, lack of verbal speech, sleep disturbances, seizures, and motor and balance impairments. It results from the loss of function of the UBE3A gene in neurons.
Currently, there are no FDA-approved treatments for Angelman syndrome, highlighting the significant unmet medical need that MVX-220 aims to address.
Clinical Trial Design
The ASCEND-AS (AAV-mediated expression in neurons for Angelman syndrome) Phase 1/2 clinical trial will evaluate the safety, tolerability, and efficacy of MVX-220. The study will include both adult and pediatric patients with various genotypes of Angelman syndrome, including rare variants such as uniparental disomy and imprinting center defects.
Preclinical studies have demonstrated that MVX-220 can restore UBE3A protein expression and ameliorate symptoms in mouse models of Angelman syndrome, providing a strong scientific rationale for advancing to human trials.
Collaborative Development Approach
MVX-220 was initially developed at the University of Pennsylvania with full support from the Foundation for Angelman Syndrome Therapeutics (FAST), which funded both the development and nonclinical research activities. The program was subsequently licensed to MavriX Bio, a portfolio company of FAST's drug development accelerator AS2Bio, to enable clinical translation.
The development is being conducted in collaboration with GEMMABio, a therapeutics company focused on developing transformative gene therapies and ensuring global access to treatments.
Jim Wilson, MD, PhD, President and CEO of GEMMABio, emphasized the significance of this milestone: "This collaboration represents the culmination of decades of partnership and scientific innovation aimed at addressing complex monogenic neurological disorders. We are excited to support MavriX Bio as they advance MVX-220 into clinical evaluation – an important milestone offering renewed hope for families affected by Angelman syndrome."
Next Steps
MavriX Bio plans to host a webinar in the coming months to provide additional details regarding the clinical trial design, eligibility criteria, and expected timelines. Registration details for the webinar will be available through the Foundation for Angelman Syndrome Therapeutics and the Angelman Syndrome Foundation.
Therapeutic Mechanism
MVX-220 is an investigational hu68AAV gene therapy designed to deliver the human UBE3A gene to neurons of the brain. The therapy aims to provide a functional copy of the UBE3A gene, potentially addressing the underlying genetic cause of Angelman syndrome.
The approach represents a significant advancement in the treatment landscape for Angelman syndrome, potentially offering a one-time treatment that could provide long-lasting benefits for patients who currently have limited therapeutic options.
As MavriX Bio moves forward with the ASCEND-AS clinical trial, the Angelman syndrome community watches with hope that this novel gene therapy approach may finally provide a transformative treatment option for this challenging neurological disorder.
