Trial GPH101 Tests Potential SCD Treatment Enrolls First Patient


The first participant was enrolled in the phase 1/2 CEDAR clinical trial evaluating Bio graphiteThe experimental gene-editing therapy of GPH101, designed to directly correct the genetic mutation that causes sickle cell disease (SCD).

“We are delighted that our first patient is now enrolled in our CEDAR clinical trial, and we look forward to evaluating the potential of GPH101 as we continue to urgently advance its development in the hope of providing a curative treatment 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 the first 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 in the blood. The therapeutic 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 experimental 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,” said Lehrer .

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

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

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

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

The main objective of CEDAR is to evaluate the safety data of GHP101, including the evaluation of stem cell transplantation, i.e. whether the modified cells are able to survive and grow. once returned to the body.

A number of efficacy measures will also be evaluated, including measuring hemoglobin levels, monitoring complications of SCD such as vaso-occlusive crises, and monitoring patient-reported outcomes.

Graphite researchers and their colleagues will present the full design of the CEDAR study next month at the 63rd Annual Meeting and Exhibition of the American Society of Hematology. Their poster presentation, “Cedar trial underway: first phase 1/2 study in humans correcting a single nucleotide mutation in autologous HSCs (GPH101) to convert HbS to HbA for the treatment of severe SCDIs scheduled for December 11.

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


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