The FDA has placed a clinical hold on LogicBio Therapeutics’ planned genome editing trial. LogicBio wants to trial the therapy in methylmalonic acidemia (MMA) patients aged two years and up but has run into resistance at the FDA.
Details of the nature of the regulatory resistance and how soon it is likely to be resolved are scarce. LogicBio provided scant information in its statement to disclose the FDA clinical hold. According to analysts at Jefferies who spoke to management at LogicBio, the lack of information in the statement reflects the fact the biotech is yet to learn what the FDA wants to see before it lifts the clinical hold.
LogicBio’s regulatory point person reportedly learned of the clinical hold during a conversation with the FDA project manager. The questions the FDA wants LogicBio to answer were not discussed on the call.
A clearer picture of the situation will emerge once the FDA submits questions to LogicBio in writing. The FDA is due to send questions within 30 days. LogicBio has vowed to work with the FDA to resolve the issues as quickly as possible, but at this stage it is unclear how long the clinical hold will drag on.
In the absence of hard facts, the Jefferies analysts speculated about the sorts of issues that may have derailed the filing. Most of the issues proposed by the analysts, such as a request for more preclinical information or a gap in the filing, are the sort of generic problems that can affect all attempts to get clearance to run a study. However, the analysts also propose a specific barrier to the study start.
LogicBio wants to test its candidate, LB-001, in MMA patients as young as two years of age. The age range targeted by the trial reflects the needs of the patients, some of whom receive liver transplants before reaching preschool age. But, while the plan may be consistent with the unmet medical need, it also requires the FDA to sign off on giving a genome editing therapy to very young patients.
In light of those factors, the Jefferies analysts said it is “not a complete surprise” that the FDA wants to subject the trial to additional scrutiny. Examples of other emerging modalities, such as Vertex and CRISPR Therapeutics’ gene-edited stem cell therapy for sickle cell disease, have also been placed on clinical hold in recent years.
Vertex and CRISPR got out from under their clinical hold in less than five months. The big questions for LogicBio are how long it will take to resolve its clinical hold and what it will take to do so. If the FDA’s concerns center on the age range targeted by the trial, LogicBio may need to initially study its drug in older patients.
That outcome would deprive LogicBio of a potential edge over Moderna, which has to test its MMA candidate mRNA-3704 in three patients aged eight years or older before enrolling younger subjects. The restriction appears to have caused Moderna problems. Last month, Moderna CEO Stéphane Bancel said the trial failed to enroll a patient in 2019, despite it getting underway in May. Moderna finally enrolled its first patient this week.
Shares in LogicBio fell around 25% in premarket trading following the news.