FDA Grants Fast Track Status to SCD Gene-editing Therapy GPH101

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by Steve Bryson, PhD |

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Graphite Bio’s GPH101, an investigational gene-editing therapy that aims to correct the genetic mutation that causes sickle cell disease (SCD) and potentially cure the condition, has been awarded fast track designation by the U.S. Food and Drug Administration (FDA).

The fast track process is designed to accelerate the development and review of new medicines or biologics that treat serious or life-threatening conditions and fulfill unmet medical needs.

The therapy’s safety and efficacy will be evaluated in the open-label Phase 1/2 CEDAR trial (NCT04819841). The trial is currently enrolling up to 15 patients at sites in Missouri, Alabama, and California, with dosing expected to begin in the second half of this year. Top-line proof-of-concept data are expected in 2023.

“The FDA’s decision to grant fast track designation to GPH101 for sickle cell disease signifies the need for novel medicines for this serious genetic disease and supports the ongoing development of our unique gene correction approach that we believe could offer a definitive cure for sickle cell patients,” Josh Lehrer, MD, CEO of Graphite Bio, said in a press release.

“This designation has the potential to accelerate the development of GPH101, which we are advancing with the goal of precisely and efficiently correcting the genetic mutation that is the underlying cause of sickle cell disease,” Lehrer said.

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Trial of Gene Editing Therapy – Potential SCD Cure – Now Recruiting

In SCD, mutations in a gene that encodes a subunit of hemoglobin — the protein that transports oxygen in the blood — cause oval-shaped red blood cells to instead acquire a sickle-like shape. As a result, these abnormal cells can block blood flow and compromise oxygen delivery to different tissues and organs, causing damage and inflammation.

GPH101 uses the gene-editing tool CRISPR-Cas9 and a natural DNA repair process to fix SCD-causing mutations. The therapy involves first collecting, from patients, cells that give rise to red blood cells called hematopoietic stem cells. These cells are modified in the lab and then returned to the same patient in the form of a stem cell transplant. This procedure may potentially cure SCD by restoring the production of normal hemoglobin.

To be eligible to participate in the first-in-human CEDAR trial, patients must have severe SCD and be between the ages of 12 and 40. Further, participants must have experienced at least four painful episodes caused by blood vessel blockage — known as vaso-occlusive crises (VOCs) — in the two years before study entry.

Also eligible are those who have had at least two episodes of acute chest syndrome in the past two years, or one in the past year. This syndrome is a lung condition characterized by chest pain, breathing difficulties, and fever.

Individuals who have received gene therapy or undergone stem cell transplants are not eligible.

“We continue to enroll patients in our Phase 1/2 CEDAR trial and expect to dose our first patient later this year, with initial proof-of-concept data anticipated next year,” Lehrer said.

In addition to safety, the study’s main goal is to determine whether gene-edited cells grow after being returned to the patient — a process known as stem cell engraftment.

Investigators also will measure gene-correction rates and total hemoglobin production, as well as assess SCD complications, including VOCs, acute chest syndrome, and other SCD-related events compared with the two years before enrollment.

The FDA previously granted orphan drug designation to GPH101. That status provides regulatory and financial support to experimental treatments for rare diseases to expedite their clinical development.