The FDA has placed a clinical hold on a LogicBio Therapeutics application to begin human testing of its experimental gene-editing therapy for a rare, inherited liver disorder.
LogicBio (NASDAQ: LOGC) disclosed the clinical hold for its gene-editing therapy, LB-001, after Monday’s market close. The Cambridge, MA-based biotech said that the hold concerns “certain clinical and nonclinical questions” for its submission. The company did not disclose any additional details about those questions.
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Shares of LogicBio fell more than 26 percent to $7.70 apiece in after-hours trading.
LogicBio is developing its gene-editing therapy as a potential treatment for methylmalonic acidemia (MMA), a disorder in which genetic mutations lead to the inability to process certain proteins and fats. The condition typically appears in infants and leads to vomiting, dehydration, an enlarged liver, failure to gain weight, and developmental delays. Current treatment for the disorder includes dietary changes, antibiotics, and in some cases a liver transplant.
The LogicBio therapy is intended to incorporate a functioning version of the methylmalonyl-COA mutase gene into the genome of a patient. The therapy is the product of the company’s GeneRide technology, which enables site-specific edits in the genome without requiring the DNA-cutting enzymes that are part of other technologies, such as CRISPR. That technology often employs the Cas-9 enzyme to cut DNA and make edits to the genome, though other enzymes can also be used.
One concern regarding DNA cutting enzymes is the potential for unwanted edits that can cause problems, or even spark other diseases such as cancer. By avoiding DNA-cutting enzymes, LogicBio contends its technology does not introduce such side effect risks. The company had planned to start a Phase 1/2 test of its MMA therapy in the first half of this year, followed by the report of preliminary data in the second half. The FDA has exercised caution as new gene-editing technologies approach clinical testing. In 2018, the regulator placed a clinical hold on the application for a CRISPR-edited sickle cell disease therapy submitted by Vertex Pharmaceuticals (NASDAQ: VRTX) and CRISPR Therapeutics (NASDAQ: CRSP). That hold was lifted less than five months later and the therapy is currently in clinical testing.
LogicBio is one of a new crop of companies aiming to develop “next-generation” approaches to gene-editing. Last month, New York-based Emendo Biotherapeutics closed a $61 million Series B round of funding to support development of its technology, which is intended to make more specific and precise edits compared to what is possible using current approaches with CRISPR. That financing was followed by a $45 million Series B round for Mammoth Biosciences. The South San Francisco-based company aims to develop diagnostics and drugs that use Cas-14, a DNA-cutting enzyme whose smaller size enables it to get to places on the genome that Cas-9 can’t.
The Emendo and Mammoth Bio technologies have not yet reached clinical testing. LogicBio was on track to beat them to the clinic after submitting the regulatory paperwork needed to start such testing last month. Now LogicBio needs to answer questions that the FDA has about the company’s clinical trial application. It expects to formally receive the regulator’s questions in writing within 30 days.