Clinical Trial Cleared for GPH101, First Potentially Curative SCD Therapy

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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The investigational gene editing therapy GPH101 will be the first potentially curative treatment for sickle cell disease (SCD) to be tested in a Phase 1/2 clinical trial.

The U.S. Food and Drug Administration (FDA) has cleared GPH101 for clinical testing. With this decision, the therapy’s developer, Graphite Bio, has now become the first company to advance to trial a lead investigational treatment that would address the disease’s underlying cause.

The new, open-label trial, called CEDAR, is designed to evaluate the safety and pharmacological properties of GPH101, as well as its preliminary efficacy in adults and adolescents with severe SCD. Patient recruitment and enrollment is expected to start soon.

“The FDA clearance to advance our first investigational therapy, GPH101, into clinical development is a tremendous milestone enabling us to rapidly advance our targeted DNA integration approach into the clinic and bringing Graphite Bio one step closer to making a difference for patients,” Josh Lehrer, MD, CEO of Graphite Bio, said in a press release.

“We are eager to initiate enrollment for the CEDAR clinical trial in early 2021, which will be a historic milestone as the first experimental treatment designed to correct the mutation that is the underlying cause of sickle cell disease,” Lehrer said.

GPH101 leverages the power of the CRISPR-Cas9 gene-editing tool, along with a natural DNA repair mechanism, to remove the mutation in the beta globin (HBB) gene that causes SCD, and replace it with the correct DNA sequence.

This is done in hematopoietic stem cells, which are the cells in the bone marrow that originate all immune cells. These stem cells are collected from the patient, engineered to produce the correct gene, and introduced back into the patient in the form of a stem cell transplant.

Through this mechanism, GPH101 may potentially cure the disease by restoring the production of normal hemoglobin — the protein that transports oxygen in the blood — and preventing red blood cells from becoming damaged and misshapen.

“GPH101 seeks to restore normal hemoglobin expression, which has been the ultimate goal of sickle cell disease treatment for more than 70 years,” Lehrer said.

Originally developed by investigators at Stanford University, in California, GPH101’s preclinical development was advanced at the Center for Definitive and Curative Medicine.

Graphite Bio recently acquired the therapy’s exclusive development rights after entering into a definitive licensing agreement with Stanford. Under the terms of the agreement, the company holds the exclusive rights for developing new gene-editing therapies to treat blood disorders caused by defects in hemoglobin and red blood cells.

“Today’s announcement represents an important step toward making gene editing by targeted DNA integration a therapeutic reality for patients,” said Matthew Porteus, MD, PhD, co-founder of Graphite Bio.

Porteus said the start of clinical trials is the “culmination of decades of research and scientific investment.”

“The scientific platform behind Graphite Bio’s pipeline was born out of a passion for improving the treatment paradigm for people with sickle cell disease, and it is my hope that this platform can one day offer a cure for this and many other devastating diseases,” Porteus added.