Phase 1/2 Trial of Gene-editing Therapy for SCD Cleared by FDA

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by Vanessa Pataia |

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The U.S. Food and Drug Administration (FDA) has cleared the start of a Phase 1/2 clinical trial testing a genome editing-based therapy, known as OTQ923, in adults with severe complications of sickle cell disease (SCD).

OTQ923, developed by Novartis and Intellia Therapeutics, uses the CRISPR/Cas9 genome-editing technology.

CRISPR/Cas9 contains two main components. One is a small piece of “guide” RNA that binds to the target DNA. The other is the Cas9 enzyme that recognizes a specific DNA sequence and cuts it at the targeted location. This cut allows the sequence of the gene to be altered (genome editing).

In the case of OTQ923, a person’s hematopoietic stem cells (stem cells that give rise to blood cells) are removed. CRISPR/Cas9 is then used to edit the genome and induce the expression of the gene coding for fetal hemoglobin — the main form of hemoglobin in fetuses that’s more efficient at transporting oxygen than the form normally found in adults. (People with SCD have alterations in hemoglobin due to a mutation in the HBB gene.)

The edited cells are returned to the patient, where the expression of fetal hemoglobin is expected to ease the disease’s symptoms.

A previous study by Intellia in a mouse model of SCD showed that using CRISPR/Cas9 in hematopoietic stem cells increased the number of red blood cells carrying fetal hemoglobin by 30% to 40%. 

After editing human hematopoietic stem cells and introducing them into these mice, the team found also that fetal hemoglobin was produced at high levels for more than 16 weeks. And researchers confirmed that the editing affected only intended gene.

“Our research with Novartis over the past five years has laid the groundwork for the development of next-generation CRISPR/Cas9-based cell therapies for patients,” Andrew Schiermeier, PhD, Intellia’s chief operating officer and executive vice president, said in a press release.

“We are pleased to have worked alongside our colleagues at Novartis to achieve this important milestone, which moves this CRISPR/Cas9-based engineered cell therapy into the clinic, with the potential to significantly impact the lives of patients who suffer from sickle cell disease,” Schiermeier added.

Novartis’ Investigational New Drug IND application triggered a milestone payment to Intellia, with the company being eligible to receive additional success-based milestones and royalties in the future.