First Patient Enrolled in GPH101 Trial Testing Potential SCD Cure

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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GPH101 trial enrolls first patient | Sickle Cell Disease News | Illustration of line chart labeled clinical trial

The first participant has been enrolled in the Phase 1/2 clinical trial CEDAR evaluating Graphite Bio’s investigational gene editing therapy GPH101, which is designed to directly correct the genetic mutation that causes sickle cell disease (SCD).

“We are thrilled that our first patient is now enrolled in our CEDAR clinical trial, and we look forward to evaluating GPH101’s potential as we continue to advance its development with urgency in hopes of delivering a curative therapy to the sickle cell community,” Josh Lehrer, MD, CEO of Graphite Bio, said in a press release.

The patient is expected to receive treatment with GPH101 early next year, with initial proof-of-concept data expected by the end of next year.

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SCD is caused by genetic mutations that lead to the production of an abnormal version of hemoglobin, the protein used to carry oxygen through the blood. The therapy candidate aims to “correct” the mutation in a patient’s blood cells, thereby allowing the production of a functional version of hemoglobin.

“GPH101 is the first investigational therapy to enter clinical development that uses our next-generation gene editing platform technology to directly correct the mutation in the beta-globin gene that causes sickle cell disease,” Lehrer said.

“Using our gene correction approach, we have demonstrated in preclinical studies an ability to decrease the production of harmful sickle hemoglobin and restore the expression of normal adult hemoglobin. This approach has the potential to restore normal physiology and is viewed as the gold standard for curing sickle cell disease,” Lehrer added.

The CEDAR trial (NCT04819841), which is sponsored by Graphite, aims to recruit approximately 15 people with SCD, ages 12 to 40, at up to five study locations. According to the trial’s page, it is currently enrolling participants at the Lucile Packard Children’s Hospital, in Palo Alto, California, and at Washington University, in Saint Louis, Missouri.

To be eligible for the trial, participants must have severe SCD — defined as at least four vaso-occlusive crises and/or at least two episodes of acute chest syndrome in the two years prior to trial enrollment. Individuals on routine infusion treatment must meet these criteria in the years before starting on infusions. The trial is not open to people who have undergone stem cell transplant or treatment with gene therapies.

After assessments to confirm eligibility, participants will undergo a procedure to collect their hematopoietic stem cells, which are the bone marrow cells that give rise to blood cells. These cells will then be gene edited and transplanted back into the patient.

The main goal of CEDAR is to assess safety data for GHP101, including assessing stem cell engraftment — that is, whether the edited cells are able to survive and grow once put back in the body.

A number of efficacy-related measures also will be assessed, including measuring hemoglobin levels, tracking SCD complications like vaso-occlusive crises, and monitoring patient-reported outcomes.

Researchers at Graphite along with colleagues will present the full design of the CEDAR study next month at the 63rd American Society of Hematology annual meeting and exposition. Their poster presentation, “Cedar Trial in Progress: A First in Human, Phase 1/2 Study of the Correction of a Single Nucleotide Mutation in Autologous HSCs (GPH101) to Convert HbS to HbA for Treating Severe SCD,” is slated for Dec. 11.

The ASH meeting will run Dec. 11-14, both virtually and at the Georgia World Congress Center, in Atlanta.