For those living with sickle cell disease (SCD), treatment and management can sometimes be difficult. Currently, there is no cure for SCD. Patients may manage their condition using antibiotics, pain relievers, hydroxyurea, blood transfusions, and – in some cases – bone marrow or blood transplants. New and more effective therapies are needed to improve the lives of those living with SCD. According to CGT Live, Graphite Bio is working towards a therapy which addresses the underlying genetic causes of sickle cell disease. This therapy, once now as GPH101 and now known as nulabeglogene autogedtemcel (nula-cel), is being evaluated in the Phase 1/2 CEDAR study. In fact, the first patient in the study was just dosed.
Altogether, 15 participants with severe SCD will enroll in the study. Participants will have experienced 4+ episodes of recurrant severe vaso-occlusive crisis or 2+ episodes of acute chest syndrome over the last two years. During the trial, participants will receive one intravenously administered nula-cel dose.
Primary end points for the trial include:
- Overall survival after two years
- How many patients have neutrophil engraftment after 42 days
- The mortality rate associated with treatment after both 100 days and 1 year
- How often – and how severely – adverse reactions occur
About Sickle Cell Disease (SCD)
Sickle cell disease (SCD) refers to a group of disorders characterized by malformed, sickle-shaped red blood cells. The most common form of SCD is sickle cell anemia. SCD is an inherited disease and is inherited in an autosomal recessive pattern. This means that patients must inherit one defective gene from each parent. In those with SCD, malformed red blood cells get caught along the walls of blood vessels, creating blockages and blood flow restrictions. People of African American descent are at a higher risk of having sickle cell disease.
Symptoms may appear within the first 5-6 months following birth. These symptoms can (but do not always) include:
- Jaundice (yellowing of the skin, eyes, and mucous membranes)
- Fatigue
- Swelling of the hands and feet
- Pain crisis
- Note: Pain crisis occurs when blood flow is blocked due to sickle cells becoming stuck. This pain often affects the chest, arms, and legs. While adults often continuously feel the effects of SCD, many children with SCD only experience other symptoms during pain crises.
- Anemia (low red blood cell count)
- Shortness of breath
- Organ damage
What is nula-cel?
A press release from Graphite Bio describes nula-cel as:
an investigational next-generation gene editing autologous hematopoietic stem cell therapy. Nula-cel is the first investigational 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 (HbS) production and restore adult hemoglobin (HbA) expression, thereby potentially curing SCD.
Preclinical research has found nula-cel to be safe and effective, improving and increasing adult hemoglobin levels. This treatment has also received both Fast Track and Orphan Drug designations. More data from the CEDAR study should be available sometime next year.
