Gene Editing Trial Underway in Pediatric Methylmalonic Acidemia


The therapy utilizes LogicBio’s GeneRide technology to insert a corrective copy of the target gene via synthetic AAV vectors.

The first patient has been dosed with LB-001 in the phase 1/2 SUNRISE trial (NCT04581785) for methlymalonic acidemia (MMA), LogicBio Therapeutics recently announced. The treatment utilizes the company’s proprietary GeneRide™ platform to deliver in vivo gene editing therapy to pediatric patients with the disease.

“Today's landmark announcement represents a significant step forward in gene editing for children suffering from early onset genetic diseases," Frederic Chereau, president and chief executive officer, LogicBio Therapeutics, said in a statement. "In addition to dosing the first patient, we have now opened several trial sites and identified enough additional patients to fully enroll SUNRISE, subject to screening clearances. We look forward to providing an update on enrollment, dose escalation, and age de-escalation in late 2021. In addition, we continue to expect to announce interim clinical data by the end of the year."

The open-label, multi-center trial is assessing the safety and tolerability of a single intravenous infusion of LB-001 in pediatric patients with MMA characterized by MMUT mutations. It is being conducted across 7 centers in the US as well as 1 in Saudi Arabia.

SUNRISE is currently enrolling patients between the ages of 3 and 12 years. This range may be expanded to include infants as young as 6 months if the first 2 patients currently enrolled meet predefined safety parameters. The expanded range of enrollment is also pending biomarker detection indicating genome integration and protein expression. The trial will enroll up to 8 patients and assess 2 dose levels. 

"Many genetic medicines are unable to target pediatric indications such as MMA, but an early and durable intervention in this vulnerable population has the potential to prevent disease progression and irreversible symptoms, including neurological damage," Daniel Gruskin, MD, chief medical officer, LogicBio, added. "Our goal is to provide a safe and durable therapeutic option to treat MMA early enough to make a meaningful difference in patients' lives and eliminate the need for invasive liver transplantation, which is increasingly performed in children suffering from this disease." 

LogicBio’s GeneRide™ platform uses homologous recombination for precision editing of the genome. The technology removes the need for exogenous nucleases and promoters associated with an increased risk of immune response and cancer. LB-001 is designed to insert a functioning copy of MMUT to the albumin locus to achieve sufficient, lifelong MMUT expression in the liver via engineered recombinant adeno-associated virus vectors (rAAV-LK03). 

The technology previously demonstrated safety as well as evidence of hepatocyte transduction, site-specific genome integration, and transgene expression in mice models during preclinical studies. Mice with the LB-001 corrected hepatocytes exhibited improved growth, metabolic stability, and survival compared with untreated mice.

Principal investigator Thomas M. Morgan, MD, of Monroe Carell Jr. Children's Hospital at Vanderbilt, also commented, saying that “this milestone takes us one step closer to bringing a much-needed treatment option to patients living with MMA. I look forward to helping advance the SUNRISE trial and seeing the results."

In an interview with GeneTherapyLive, Gruskin and chief scientific officer Mariana Nacht, PhD, provided details on the proprietary gene editing platform and why their approach presents an advantage—both in safety and efficacy—compared with other gene therapy models. Watch the interview below:

LogicBio Therapeutics announces first patient dosed in groundbreaking phase 1/2 SUNRISE clinical trial for the treatment of pediatric patients suffering from methylmalonic acidemia. News release. LogicBio Therapeutics. June 2, 2021.
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