In-Vivo Genome Editing Therapy Shows Efficacy in Children With MMA


The phase 1/2 SUNRISE trial is now enrolling patients as young as 6 months old with methylmalonic acidemia after positive review under a DSMB.

LB-001, LogicBio Therapeutics’ in-vivo genome editing therapy, has shown efficacy in children with methylmalonic acidemia (MMA), according to new data announced from the phase 1/2 SUNRISE trial (NCT04581785).

The phase 1/2 trial has demonstrated site-specific gene insertion and protein expression via albumin-2A biomarker expression in children with MMA treated with LB-001. An independent Data Safety Monitoring Board (DSMB) has recommended the trial safe to continue based on safety data from the first 2 patients enrolled.

“We are very excited to have achieved this significant milestone in the field of genetic medicine," said Fred Chereau, president and chief executive officer, LogicBio, in a statement. "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. 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 open-label, multi-center SUNRISE trial is evaluating the safety, tolerability, and preliminary efficacy of a single administration of LB-001 in pediatric patients with MMA with mutations in the MMUT gene. The trial is being conducted across 7 centers in the US and 1 in Saudi Arabia. 

READ MORE: Prime Medicine Takes Precise Approach to Gene Editing With “Find and Replace” Technology

SUNRISE, which is currently enrolling, initially recruited patients between 3 and 12 years of age, but this has since been expanded to allow infants as young as 6 months of age to enroll due to a recommendation from the DSMB. The trial plans to enroll up to 8 patients and evaluate 2 dose levels of LB-001. LogicBio will soon enroll 2 patients in the higher dose (1 x 1014 vg/kg) cohort of participants between 3 and 12 years of age and 2 patients between 6 months to 2 years old in the lower age, lower dose (5 x 1013 vg/kg) cohort.

“MMA is a rare, life-threatening genetic disorder for which there are no treatments addressing the underlying cause of the disease. By demonstrating for the first time ever that in vivo, nuclease-free genome editing in pediatric patients is achievable, we are one step closer to bringing a safe and effective genetic medicine to children suffering from MMA and, potentially, other early onset genetic diseases where early intervention is critical to achieve optimal health outcomes," Daniel Gruskin, MD, chief medical officer, LogicBio, added to the statement. "I would like to thank the patients, their families and the investigators who are participating in this landmark trial. We look forward to continuing to progress the clinical study to better understand the biochemical and clinical effect of this genome editing therapy."

LogicBio’s gene therapy is designed to induce a durable expression of therapeutic levels of the MMUT gene in the liver by inserting a corrective copy of the gene to the albumin locus. The therapy is delivered intravenously to hepatocytes by a liver-targeted, engineered recombinant adeno-associated virus vector (rAAV-LK03).

LB-001 uses the company’s proprietary GeneRide technology, which uses homologous recombination to achieve precise editing of the genome. The therapy, which does not use exogenous nucleases and promoters, is designed to be better tolerated than other gene therapies that have been associated with increased risks of immune response and cancer. Preclinical studies have previously demonstrated MMUT expression in a mouse model of MMA leading to improved growth, metabolic stability, and survival.

"The GeneRide technology is particularly well suited for diseases where early intervention is clinically important. And so, this is why MMA was chosen,” Gruskin previously told GeneTherapyLive.

The FDA previously granted LB-001 fast track designation, rare pediatric disease designation and orphan drug designation (ODD) for the treatment of MMA. The EMA has also granted ODD to the therapy for the same indication.

LogicBio Therapeutics Announces Early Clinical Trial Results Demonstrating First-Ever In Vivo Genome Editing in Children. News release. LogicBio Therapeutics. October 18, 2021.
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