Trial of next-generation SMA gene therapy GB221 doses first patient
Phase 1/2 study will assess safety and developmental outcomes in infants
Written by |
- A Phase 1/2 clinical trial has begun testing GB221, a next-generation gene therapy for SMA type 1.
- GB221 is designed to deliver a working SMN1 gene through an injection into the cisterna magna.
- The CHARISMA study is enrolling infants ages 2 weeks to under 1 year with SMA type 1 to assess safety and development.
The first patient has been dosed in a clinical trial testing GB221, a next-generation gene therapy for spinal muscular atrophy (SMA) type 1.
“I would like to express our gratitude for the young child and family who were courageous in being the first to accept our investigational gene therapy for SMA1,” James M. Wilson, MD, PhD, CEO of GB221’s developer, Gemma Biotherapeutics, said in a company press release.
SMA is a genetic disorder caused primarily by mutations in the SMN1 gene. These mutations lead to the degeneration and loss of motor neurons, the nerve cells that control movement. GB221 uses a viral vector to deliver a working copy of the SMN1 gene to motor neurons. The therapy includes design modifications intended to help better control SMN1 expression and reduce the risk of unwanted effects in non-target nerve cells. GB221 is administered by an injection into the cisterna magna, a fluid-filled space at the base of the skull near where the brain connects to the spinal cord.
Preclinical studies support advancement into clinical testing
In a mouse model of SMA, GB221 was associated with improved survival and neuromotor function. In non-human primate studies, the therapy enabled delivery of the therapeutic gene to motor neurons with no observed toxicity.
The Phase 1/2 CHARISMA study (NCT07070999), sponsored by Gemma, is expected to enroll 22 infants with SMA ranging in age from 2 weeks to younger than 12 months. To be eligible, participants must have a confirmed genetic diagnosis of SMA caused by SMN1 mutations and no more than three copies of the SMN2 gene, which can partially compensate for missing SMN1. In general, individuals with more SMN2 copies tend to have milder forms of SMA, while those with SMA type 1 typically have one or two copies.
The study includes infants who are already showing symptoms of SMA type 1, as well as babies younger than 5 months who have been diagnosed but have not yet developed clear symptoms. All participants will be treated with GB221. The primary goals are to assess safety and tolerability, along with measures of physical and neurological development. The study is being conducted at clinical sites in Brazil.
“The medical team is monitoring the first patient carefully, hoping to see therapeutic benefit and progress towards developmental milestones,” said Jonas Morales Saute, MD, PhD, the trial’s principal investigator at the Hospital de Clínicas de Porto Alegre in Brazil. “We are excited to leverage our experience in genetic diseases and clinical research to accelerate the development and evaluation of genetic medicines for other rare diseases.”
Study conducted in Brazil through local collaboration
Gemma is conducting the study in collaboration with the Oswaldo Cruz Foundation (Fiocruz), a public health research institution based in Brazil.
“The ongoing clinical study opens a front of action that can transform the lives of families and children who deal with the disease on a daily basis,” said Mario Moreira, PhD, president of Fiocruz. “The technology incorporation agreement also guarantees the opening of pathways for access to an innovative gene therapy for the first time in the Unified Health System [Brazil’s publicly funded health care system].”
The U.S. Food and Drug Administration (FDA) has granted GB221 rare pediatric disease designation, which provides incentives for companies developing treatments for serious rare diseases affecting children. If GB221 is ultimately approved in the U.S., Gemma would be eligible to receive a priority review voucher, which could be used to speed up FDA review of another application or be transferred to another company.
