MVX-220 Angelman gene therapy trial enters first human testing
Study starts dosing participants after FDA designations support development
The first patient has been dosed in a Phase 1/2 clinical trial testing MavriX Bio’s experimental gene therapy, MVX-220, in people with Angelman syndrome.
The ASCEND-AS trial (NCT07181837) will assess the safety and efficacy of the gene therapy in 12 children and adults with Angelman syndrome caused by specific UBE3A-related genetic variants. The study, the first gene therapy trial for Angelman syndrome, is recruiting participants at two sites in the U.S.
MVX-220 was recently granted orphan drug designation by the U.S. Food and Drug Administration (FDA). The designation provides regulatory support, potential financial incentives, and up to seven years of market exclusivity if the therapy is eventually approved.
First participant dosed as Phase 1/2 study begins
“Dosing our first participant in the ASCEND-AS trial is a critical step in evaluating the potential of gene-targeted therapies for [Angelman syndrome], made possible by the unwavering dedication of the Angelman community, our scientific collaborators, and development partners,” Jennifer Panagoulias, MavriX Bio’s chief operating officer, said in a press release. “This milestone, combined with the recent receipt of Orphan Drug Designation from the FDA, reinforces the promise of MVX-220 and the urgency driving our work.”
Angelman syndrome is caused by genetic abnormalities that result in the absence or dysfunction of the maternal copy of the UBE3A gene. The loss of activity of this gene — and the resulting loss of the UBE3A protein, which is crucial for brain development — leads to the neurological symptoms of the disease.
MVX-220 is a gene replacement therapy designed to deliver a healthy copy of the UBE3A gene to brain cells. It is packaged in a harmless adeno-associated virus (AAV) vector that helps carry the gene into brain cells.
ASCEND-AS will first enroll adults ages 18 to 50, followed by children, ages 4 to 8. An independent data safety monitoring board will review adult safety data before children can join the study. Based on the results from these two groups, a third optional cohort may include either adults, children, or both.
All participants will receive a single dose of MVX-220 injected into the cisterna magna, a fluid-filled space at the base of the skull. Before and after the procedure, patients will receive short-term steroid medications to prevent immune reactions to the therapy. Participants will then be followed five years.
What the ASCEND-AS trial will measure
The trial’s main goal is to assess the number and type of adverse events over the first two years. Secondary measures include changes in communication skills, motor and cognitive milestones, adaptive behaviors, and clinician-reported changes in symptom severity.
Researchers will also assess brain electrical activity using electroencephalogram and measure walking ability with a wearable movement-tracking device. Caregiver-reported outcomes will track changes in behavior, sleep patterns, and quality of life.
Elizabeth Berry-Kravis, MD, PhD, professor at Rush University Medical Center and principal investigator for the ASCEND-AS trial, said, “for the first time, we are testing a one-time therapeutic approach that directly targets the genetic root cause of Angelman syndrome by replacing UBE3AÂ expression in neurons. This is a meaningful step forward for the entire Angelman community, serving as an example for other genetic neurodevelopmental disorders.”
MVX-220’s development was supported by the Foundation for Angelman Syndrome Therapeutics (FAST), which launched MavriX Bio earlier this year to advance it into clinical studies. MavriX Bio is managed through AS2Bio, the therapeutic accelerator launched by FAST.
MVX-220 was also recently granted the FDA’s fast track designation, which is intended to speed clinical development through more frequent meetings with the agency and the possibility of accelerated review.
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