During the Phase 1/2 SUNRISE clinical trial, which evaluated LB-001 for pediatric patients with methylmalonic acidemia, at least two participants experienced serious and severe adverse reactions: thrombotic microangiopathy. While investigating the reasoning behind these reactions, the FDA placed a clinical hold on the Investigational New Drug (IND) application for LB-001. This meant that the clinical trial could not proceed, nor could additional participants enroll. However, shares LogicBio Therapeutics (“LogicBio”) in a May 9th news release, the FDA has lifted the clinical hold; patients are now able to enroll again, and LogicBio is able to begin dosing patients.
The SUNRISE Trial
Within the Phase 1/2 SUNRISE clinical trial, LogicBio is evaluating a singular intravenously administered dose of LB-001 for pediatric patients with methylmalonic acidemia. Patients between ages 6 months to 12 years can enroll. Throughout the trial, researchers hope to understand more about the treatment’s safety, efficacy, and tolerability.
LB-001 is an investigational genome editing therapy which uses LogicBio’s GeneRide platform. The company explains how GeneRide works on its website. This treatment, which has received Orphan Drug designation in Europe and the United States, as well as Fast Track and Rare Pediatric Disease designations in the U.S., inserts a functional and corrective MMUT gene. In preclinical studies, LB-001 has shown promise in stabilizing metabolism, as well as improving overall survival.
Data from this study should be available by the end of the year, if not sooner.
What is Methylmalonic Acidemia?
A variety of genetic mutations are associated with methylmalonic acidemia, including MUT, MMAA, MMAB, MMADHC, and MCEE. Methymalonic acidemia exists under the greater umbrella of organic acidemia. This rare disorder causes the body to be unable to process certain proteins and lipids. As a result, blood and body tissues have a higher and sometimes toxic level of acid. Methylmalonic acidemia is considered an inborn error of metabolism. Infants born with this condition may appear normal at birth, with symptom onset occuring within the first few months to the first year of life. Symptoms can include:
- Acidosis (overproduction of acid in the blood)
- Progressive encephalopathy
- Developmental delays
- Failure to thrive
- Respiratory distress
- Liver enlargement
- Low blood sugar (on lab findings)
- Abnormally high amounts of methylmalonic acid, ketone bodies, or ammone in the blood/urine (on lab findings)
- Low white and red blood cell, and platelet, concentrations