LogicBio Reports Data from First In Vivo Genome Editing Therapy in Kids

LogicBio Therapeutics reported early data from a phase 1/2 study of its experimental genome editing therapy for the rare metabolic condition methylmalonic acidemia, the first-ever results from in vivo genome editing therapy in children.

Photo: Fred Chereau, president and CEO of LogicBio

The company said the early data from its SUNRISE clinical trial showed measurable levels of albumin-2A, a technology-related biomarker indicating site-specific gene insertion and protein expression.

Methylmalonic acidemia (MMA) is a life-threatening genetic disorder. In the most common form of MMA, a mutation in a gene called methylmalonyl-CoA mutase (MMUT) prevents the body from properly processing certain fats and proteins. As a result, toxic metabolites accumulate in the liver, in muscle tissue and in the brain. Symptoms include vomiting, lethargy, seizures, developmental delays, and organ damage. There is no approved medical therapy addressing the underlying cause of the disease.

To manage the symptoms, patients go on a severely restrictive, low-protein, high-calorie diet, often through a feeding tube. Even with aggressive management, these patients often experience life-threatening metabolic crises that can require recurrent hospitalizations and cause permanent neurocognitive damage. Because of this risk for irreversible damage, early intervention is critical, and newborns are screened for MMA in every state in the United States.

LB-001 is an investigational, first-in-class, single-administration, genome editing therapy for early intervention in MMA using LogicBio’s proprietary GeneRide drug development platform. GeneRide technology utilizes a natural DNA repair process called homologous recombination that enables precise editing of the genome without the need for exogenous nucleases and promoters that have been associated with an increased risk of immune response and cancer.

LB-001 is designed to non-disruptively insert a corrective copy of the methylmalonyl-CoA mutase (MMUT) gene into the albumin locus to drive lifelong therapeutic levels of MMUT expression in the liver, the main site of MMUT expression and activity. LB-001 is delivered to hepatocytes intravenously via liver-targeted, engineered recombinant adeno-associated virus vector.

The U.S. Food and Drug Administration granted Fast Track, Rare Pediatric Disease, and Orphan Drug designations for LB-001 for the treatment of MMA. In addition, the European Medicines Agency granted Orphan Drug designation for LB-001 for the treatment of MMA.

The SUNRISE trial is an open-label, multi-center, phase 1/2 clinical trial designed to assess the safety and tolerability of a single intravenous infusion of LB-001 in pediatric patients with MMA characterized by methylmalonyl-CoA mutase gene (MMUT) mutations. The SUNRISE trial is designed to enroll up to eight patients and evaluate a single administration of LB-001 at two dose levels.

The results follow a recommendation from the independent Data Safety Monitoring Board overseeing the SUNRISE trial to continue the study without modification. The board’s recommendation was based on an evaluation of the safety data from the first two patients enrolled in the trial. Per the FDA-cleared protocol, albumin-2A detection together with the board’s continuation recommendation enables LogicBio to begin enrolling two patients in the higher dose cohort (with ages ranging three to twelve years old) and two patients in the lower age (six months to two years old) cohort at the lower dose of LB-001.

“These early data indicate that we can precisely edit hepatocytes in vivo to treat a genetic liver disease with a single intravenous infusion using our proprietary GeneRide technology,” said Fred Chereau, president and CEO of LogicBio. “Today’s announcement is a demonstration that homologous recombination genome editing without the use of nucleases is a potential alternative to genome editing technologies in development that use nucleases, such as CRISPR. The ability to insert the correct version of a gene in a cell’s genome without nucleases is an important step to unlocking the potential of GeneRide to treat a larger number of genetic diseases.”

The company said it remains on track to present additional interim data by the end of 2021.

Author: Rare Daily Staff