Gene Repair Therapy: First Patient Dosed With New Treatment for Sickle Cell Disease

On August 11, Graphite Bio announced that they dosed their first patient with GPH101. GPH101, otherwise referred to as nula-cel (nulabeglogene autogedtemcel), is a gene repair treatment for sickle cell disease. The therapy is currently under analysis in the Phase ½ CEDAR clinical trial. Gene Repair of Sickle Cell Disease has the potential to nullify need for hemoglobin polymerization inhibitors.

Related Article: CRISPR Biotech Editas Obtains FDA Rare Pediatric Disease Label

The Current Treatments of Sickle Cell Disease

Sickle cell disease is a devastating blood disorder wherein a patient’s blood cells change into a sickle shape. As a result, the sickle blood cells lack a healthy cell’s capacity for carrying oxygen—that lack of oxygen results in low levels throughout the body. In addition, patients experience chronic symptoms like joint pain, dizziness, inflammation, and shortness of breath. 

Sickle cell disease is a chronic condition caused when a person inherits two defective hemoglobin genes from each parent. When someone inherits only one sickle cell gene, known as hemoglobin S, that individual is generally healthy. However, when two hemoglobin S genes, or one and another faulty hemoglobin gene, are inherited, that person develops sickle cell disease. As a result, the available medicines only treat the symptoms of sickle cell disease. 

An example of one of these treatments is Droxia (hydroxyurea). Produced by Bristol Myers Squibb, Droxia inhibits an enzyme known as ribonucleotide reductase, resulting in a reduced chance of sickle cells forming. 

However, nula-cel could be a treatment that repairs the broken gene causing sickle cell formation in the first place. 

Repairing the Cause of SCD

Nula-cel works by directly editing the gene mutation causing sickle cell disease with CRISPR technology. As a result of this edit, hemoglobin would begin to produce healthily shaped cells rather than sickled ones. Currently, the Phase ½ CEDAR Trial is evaluating the safety, preliminary efficacy, and pharmacodynamics of nula-cel. Fifteen participants affected by severe sickle cell disease are the subjects of the trial.

Josh Lehrer, M.D., M.Phil., chief executive officer of Graphite Bio, said, “We continue to make tremendous progress with the development of nula-cel, which in preclinical studies successfully corrected the sickle cell disease mutation, directly reducing sickle hemoglobin and restoring healthy adult hemoglobin to potentially curative levels.”

Should the trial results prove fruitful, Graphite Bio might have a contender for sickle hemoglobin polymerization inhibitors like Droxia and Global Blood Therapeutics’ Oxbryta. 

Graphite Bio expects the CEDAR trial to conclude its findings of nula-cel in May 2026. 

Related Article: Pfizer Acquires Global Blood Therapeutics and its sickle cell disease expertise for $5.4 billion

Author

Max Heirich