LogicBio’s Methylmalonic Acidemia Gene-Editing Therapy Program Placed on Clinical Hold
The hold was prompted by the second development of a serious AE of thrombotic microangiopathy in a patient in the younger age group.
The FDA has placed a clinical hold on LogicBio Therapeutics' phase 1/2 SUNRISE trial (NCT04581785) of LB-001 for the potential treatment of methylmalonic acidemia (MMA).1
The clinical hold comes after the fourth patient dosedwith 5 x 1013 vg/kg LB-001 in the SUNRISE trialexperienced a treatment-related serious adverse event (AE) of thrombotic microangiopathy (TMA) in January 2022. The new incidence of TMA follows the same AE in the third patientdosed in November 2021, meaning that both patients in the younger age group of 6 months to 2 years old have now experienced TMA.2
"Patient safety is our first priority. I would like to thank the patient and the patient's family for participating in our trial as well as the on-site team for the excellent care they are providing," Fred Chereau, president and chief executive officer, LogicBio, said in a statement.1 "We look forward to working closely with the FDA and the DSMB to determine the next steps for the trial and the program."
WATCH NOW: Gene Editing Trial Underway in Pediatric Methylmalonic Acidemia
The first 2 patients treated with the same dose of 5 x 1013 vg/kg of LB-001 in the older age group of 3 to 12 years have not experienced treatment-related serious AEs. The TMA experienced by the third patient has completely resolved as of December 2021.
LogicBio previously planned to announce interim data from the SUNRISE trial by the second quarter of 2022, but these plans will be suspended due to the clinical hold. The company is communicating with the FDA to determine the next steps for the LB-001 program and any protocol amendments.
LB-001 is developed using LogicBio's proprietary GeneRide platform, which uses homologous recombination to edit the genome without exogenous nucleases and promoters. The therapydelivers a corrected MMUT gene intravenously to the liver. The FDA previously granted fast track, rare pediatric disease, and orphan drug designations to the therapy for the treatment of MMA.The EMA has also granted ODD to the therapy for the same indication.
The younger age group was previously added to the study after a positive review from the independent data safety monitoring board in October 2021.3 Data announced at that time from the SUNRISE trial demonstrated site-specific gene insertion and protein expression via albumin-2A biomarker expression.
