FDA puts LogicBio genome editing therapy trial on hold after 2nd infant suffers adverse event

LogicBio Therapeutics’ bid to develop a genome editing therapy in infants has hit more trouble. Months after the first infant to receive the therapy suffered a serious adverse event, LogicBio has revealed the second subject has experienced the same clinical syndrome, prompting the FDA to impose a clinical hold. 

The phase 1/2 trial initially enrolled two older children, aged three to 12 years, with the life-threatening inherited disorder methylmalonic acidemia. LogicBio safely dosed the older children with LB-001, an AAV genome editing therapy designed to insert the methylmalonyl-CoA mutase gene, and expanded the trial to include infants aged six months to two years. That is when the problems began.

Last year, LogicBio reported the first younger recipient of LB-001 developed thrombotic microangiopathy, a condition defined by the destruction of red blood cells, low platelets and organ damage. The patient was hospitalized, but the adverse event had resolved by the end of the year.

After seeing the patient recover, LogicBio administered LB-001 to a second infant in January. That infant also suffered thrombotic microangiopathy. When the FDA learnt of the second serious adverse event, it put the trial on clinical hold. The FDA previously put the study on hold in 2020.

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LogicBio is now working with the FDA to figure out the next steps for the clinical trial. Based on the four patients treated so far, the issue appears to be limited to young infants. However, with methylmalonic acidemia requiring some patients to undergo organ transplants before reaching preschool age, LogicBio needs to target infants to maximize the impact of the therapy.

Equally, LogicBio may have limited wiggle room on dosing. The serious adverse events happened at the lower of the two doses LogicBio plans to study. LogicBio had previously outlined plans to test the higher dose for the first time in an older child.

It is unclear when the FDA will clear LogicBio to resume dosing. Given the uncertainty, LogicBio is no longer forecasting that it will report additional interim data from the clinical trial in the second quarter. 

Delayed data could have severe consequences for LogicBio. As of the end of September, LogicBio had just shy of $60 million in the bank, a sum it predicted would see it into the fourth quarter of 2022. LogicBio’s stock fell again in response to the clinical hold, tumbling 25% in premarket trading to just above $1.