RARE Daily

FDA Places Hold on LogicBio’s Trial of LB-001 for the Treatment of Pediatric Patients with MMA

February 2, 2022


The U.S. Food and Drug Administration place a hold on LogicBio Therapeutics’ phase 1/2 SUNRISE clinical trial of AAV-delivered gene editing therapy LB-001 in pediatric patients with methylmalonic acidemia after two patients were diagnosed with the formation of blood clots.

Shares of the biotech fell 34 percent on the news.

To date, four children have been dosed in the SUNRISE trial with LB-001, the company said. In accordance with the FDA-cleared protocol, the first two patients dosed were in the older age group (3 to 12 years old) and received 5 x 1013 vg/kg of LB-001. These first two patients are doing well, have not experienced drug-related serious adverse events (SAEs), and are being monitored in accordance with the protocol.

As previously disclosed, the third patient dosed in the SUNRISE trial, who received 5 x 1013 vg/kg of LB-001 and is in the younger age group (6 months to 2 years old), experienced a drug-related SAE, which was categorized as a case of thrombotic microangiopathy (TMA), or tiny clots in blood vessels. TMA has been previously reported in association with other AAV genetic therapies. The patient was hospitalized and responded well to intravenous fluids and parenteral nutrition. Following this SAE, the company implemented additional safety measures in the SUNRISE trial and reported the SAE to the FDA and the Data Safety Monitoring Board for the trial. The SAE experienced by the third patient resolved in December 2021.

In January 2022, the fourth patient dosed in the SUNRISE trial, who received 5 x 1013 vg/kg of LB-001 and is in the younger age group, experienced a drug-related SAE, which was categorized as a case of TMA. The patient is being closely followed by the patient’s care team and has been steadily improving. The company reported the SAE to the FDA and the Data Safety Monitoring Board. The FDA subsequently notified the company that the SUNRISE trial has been placed on clinical hold.

Methylmalonic acidemia (MMA) is a rare monogenic disorder in which the body cannot break down certain proteins and fats. This metabolic disease may lead to hyperammonemia and is associated with long-term complications including feeding problems, intellectual disability, chronic kidney disease and inflammation of the pancreas. Symptoms of MMA usually appear in early infancy and vary from mild to life threatening. Without treatment, MMA can lead to coma and in some cases death.

LB-001 is an experimental, 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 (rAAV-LK03).

Preclinical studies found that LB-001 was safe and demonstrated transduction of hepatocytes, site-specific genomic integration, and transgene expression. LB-001–corrected hepatocytes in a mouse model of MMA demonstrated preferential survival and expansion (selective advantage), thus contributing to a progressive increase in hepatic MMUT expression over time. LB-001 resulted in improved growth, metabolic stability, and survival in MMA mice. The FDA has granted Fast Track designation, Rare Pediatric Disease Designation and Orphan Drug designation for LB-001 for the treatment of MMA. In addition, the European Medicines Agency (EMA) granted orphan drug designation for LB-001 for the treatment of MMA.

LogicBio will be working closely with the FDA and the DSMB to determine the next steps for the SUNRISE trial and the LB-001 program. Until the company has more clarity regarding the impact of the clinical hold, LogicBio said it is suspending guidance on the timing of announcing interim data for the SUNRISE trial.

Stay Connected

Sign up for updates straight to your inbox.