Graphite Bio’s ambitions to use gene editing to treat sickle cell anemia have suffered a setback. The first patient given the experimental therapy developed a serious blood complication, leading the company to clinical trial pause.
The problem, which Graphite Bio characterized as a “serious and unexpected adverse event,” was pancytopenia, a decrease in the number of blood cells. This complication requires treatment with blood transfusions and growth factors to raise this number. The FDA has been notified of the complication, which the company says is likely related to its experimental treatment. Although the regulator has not placed a clinical hold on the study, South San Francisco-based Graphite Bio is putting it on hold for now as it continues to evaluate the adverse event.
“Although the event did not meet the requirements to suspend the study, based on the developing clinical data, Graphite Bio has decided to voluntarily pause the study,” the company said in a statement after the market closed on Thursday.
Sickle cell disease results from a genetic mutation that causes red blood cells to take on a crescent shape, which slows or blocks blood flow and leads to anemia, among other problems. There are medications to treat the disorder. Oxbryta, developed by Global Blood Therapeutics (acquired last year by Pfizer for $5.4 billion) addresses the underlying cause of the disease, but this small molecule drug must be taken chronically. Graphite Bio is one of several biotech companies developing genetic medicines designed for single treatments.
Graphite Bio’s therapy, nulabeglogene autogedtemcel (nula-cel), is made by ex vivo editing a patient’s hematopoietic stem cells to correct the mutation that causes sickle cell disease. These CRISPR-edited cells are then infused back into the patient. By replacing enough of the patient’s hematopoietic stem cells with these gene-corrected cells, the approach is hoped to lead to a cure for the blood disorder.
The Phase 1/2 trial of nula-cel enrolled its first patient last August. Despite the reported blood complication in this patient, Graphite Bio pointed to some encouraging signs for his therapy. This patient achieved neutrophil engraftment, the production of new white blood cells, which is an indication that the procedure worked. The company also noted that there were no signs of myelodysplasia, a rare blood cancer.
However, the clinical trial pause means Graphite Bio will miss its mid-year goal of providing initial human proof-of-concept data for nula-cel. The setback also affects another program the company is preparing. Graphite Bio said it no longer expects to file a new drug application in mid-2024 for GPH102, a gene-editing therapy for the rare blood disorder beta thalassemia.
The company added that it is working to “identify operating efficiencies” to extend its cash position through at least 2026, language that typically portends layoffs or corporate restructuring. Graphite Bio said it will provide a business update by the end of the current quarter. Shares of Graphite Bio fell more than 42% on Friday morning.