FDA slaps a hold on LogicBio and its gene editing plans — shares tumble
The FDA tends to err on the side of caution with new therapeutic approaches. LogicBio — with its experimental technique engineered to harness the cell’s natural DNA repair process to integrate a corrective gene directly into patients chromosomes — is the latest in the agency’s crosshairs.
The company — which recently had a meeting with the FDA ahead of its application to begin trials in humans with its lead experimental therapy for the treatment of methylmalonic acidemia (MMA) — has been slapped with a clinical hold on the program, pending the resolution of certain clinical and nonclinical questions.
The Cambridge, Massachusetts-based biotech’s shares $LOGC were down nearly 26% at $7.75 in Tuesday premarket trading.
LogicBio expects that the FDA questions on the therapy — LB-001 — will be provided in writing within 30 days, it said on Monday.
The FDA’s issues could pertain to a request for additional info, items missing from the IND submission, CMC issues, or even a request asking the company to initially focus on a higher age group of patients, Jefferies analyst Maury Raycroft wrote in a note, explaining that “it is not uncommon for novel/innovative first-in-human INDs” to get a clinical hold.
LogicBio was planning to kick off the study in patients with MMA — an inherited disorder in which the body is unable to process certain proteins and lipids properly — as young as age 2, given that liver transplants are recommended for patients as young as 1. Getting the FDA to sign off on patients this young would have been an edge over mRNA drug developer Moderna Therapeutics, which is also running a trial in MMA, albeit with older patients and is having difficulties with enrollment, Raycroft added.
“Our view has been that FDA would not put LOGC in a similar situation, where they cannot enroll and prevent MMA pts from getting a novel potentially transformative tx.”
LogicBio is relying on its GeneRide technology to target rare liver disorders. In contrast to traditional gene editing and gene therapy approaches, the technology has been devised to exploit the cell’s natural DNA repair process — homologous recombination — to sneak in, via a viral vector, a corrective copy of the gene at a precise spot in a patient’s genome.
The company is using the LK03 AAV vector, which has been derisked by Spark Therapeutics (now Roche’s) pioneering eye gene therapy Luxturna — and the FDA appears to be comfortable with it, Raycroft noted.
“At this point, we have little visibility on the simplicity/complexity of the questions underlying the hold, making it challenging to estimate potential timelines to resolution. We note, as with other novel platforms, clinical holds on IND applications are not foreign to the genome-editing space,” Chardan analysts wrote in a note.
For instance, in May 2018 CRISPR Therapeutics and partner Vertex’s experimental sickle cell disease therapy — engineered using CRISPR/Cas9 technology — was put on hold. By October it was lifted — and by November the following year — the collaborators unveiled positive data.
“While the hold on LB-001 is likely to delay timelines to catalysts, perhaps by a few months (e.g. we now see <50% likelihood of data by end-20), without further detail, we do not believe it necessarily impacts the overall POS of the program,” the Chardan analysts added.
LogicBio — whose IPO in 2018 was managed by both Jefferies and Chardan among other investment banks — tied up with Japan’s Takeda last month to develop LB-301 for the treatment of Crigler-Najjar syndrome, which is characterized by toxic levels of bilirubin in the blood.