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Graphite Pauses Sickle Cell Study Following Serious Adverse Event

January 6, 2023

Graphite Bio said it is voluntarily pausing the phase 1/2 CEDAR study of its experimental gene edited hematopoietic stem cell therapy nulabeglogene autogedtemcel (nula-cel) for patients with the rare blood disorder sickle cell disease following a serious adverse event in the first patient dosed with the therapy.

Photo: Josh Lehrer, CEO of Graphite Bio

The company said the event is likely related to study treatment.

Nula-cel, formerly GPH101, is an investigational next-generation gene editing autologous hematopoietic stem cell therapy designed to directly correct the genetic mutation that causes sickle cell disease (SCD). Nula-cel is the first experimental therapy to use a highly differentiated gene correction approach that seeks to efficiently and precisely correct the mutation in the beta-globin gene to decrease sickle hemoglobin production and restore adult hemoglobin expression, thereby potentially curing SCD. The U.S. Food and Drug Administration granted Fast Track and Orphan Drug designations to nula-cel for the treatment of SCD.

Shares of Grapahite Bio fell more than 40 percent in trading on Friday to $1.80 as the company said it will not meet its guidance for initial proof-of-concept data in mid-2023. Based on the ongoing activities in the nula-cel program, Graphite Bio also said it no longer expects to file an investigational new drug application for GPH102 in beta-thalassemia by mid-2024.

The patient in the study who had been given a dose of nula-cel suffered unexpected and prolonged low blood cell counts and required ongoing transfusion and growth factor support. The event has been reported to the FDA.

The patient achieved study-defined neutrophil engraftment and has shown no evidence of myelodysplasia, a rare type of blood cancer. While the event did not meet study stopping requirements, based on evolving clinical data, Graphite Bio decided to voluntarily pause the study.

Graphite Bio said it is assessing the adverse event, risk factors, and mitigation strategies, including potential modifications to the nula-cel manufacturing process. The clinical investigators and Safety Monitoring Committee for the CEDAR study have agreed with the company’s decision to suspend dosing of additional patients pending this assessment.

“The safety of every patient who participates in our clinical studies and is treated with our therapies is our absolute highest priority,” said Josh Lehrer, CEO of Graphite Bio. “We are committed to working closely with our scientific and clinical experts to fully assess this event and identify a potential path to resume the CEDAR study.”

The company is also working to identify operational efficiencies to extend its cash position to at least 2026.

Author: Rare Daily Staff

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