お知らせ • Jul 02
Vertex Pharmaceuticals Incorporated Receives Us Fda Approval for Expanded Use of Casgevy for Treatment of People Ages 2 Years and Older with Sickle Cell Disease or Transfusion-Dependent Beta Thalassemia
Vertex Pharmaceuticals Incorporated announced that the U.S. Food and Drug Administration (FDA) has approved expanded use of CASGEVY (exagamglogene autotemcel) for the treatment of people ages 2 years and older with either sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT. Approximately 5,500 additional children in the U.S. are now eligible for this established one-time therapy, expanding upon the prior FDA approval in people 12 years and older. Regulatory review for label expansion is underway in the Kingdom of Saudi Arabia and United Kingdom. Vertex has established a network of independently operated, authorized treatment centers (ATCs) throughout the U.S. to offer CASGEVY to eligible patients through existing access and reimbursement pathways. There are more than 75 activated ATCs in the U.S. Sickle cell disease (SCD) is a rare serious, inherited blood disease that is progressive and life-shortening. The disease causes red blood cells to become rigid and misshapen, restricting blood flow and oxygen delivery to vital organs. Recurrent vaso-occlusive crises (VOCs), unpredictable episodes of severe pain caused by blocked blood vessels, are a defining feature of SCD and frequently require hospitalization. Many patients experience these complications early in life, and over time, repeated VOCs and chronic anemia lead to progressive and irreversible organ damage, including damage to the brain, lungs, kidneys and heart. SCD places a substantial burden on patients and their families, who must manage frequent medical visits, hospitalizations, school and work disruptions, and the emotional toll of chronic pain and life-threatening complications. Despite lifelong treatment, people with SCD and recurrent VOCs in the U.S. face shortened life expectancy, with a median age of death of approximately 45 years, report quality-of-life scores far below the general population and the estimated lifetime healthcare costs of managing the disease are $4–6 million. Transfusion-dependent beta thalassemia (TDT) is a rare serious, inherited blood disease that is progressive and life-shortening. The disease impairs the body’s ability to produce sufficient hemoglobin, limiting oxygen delivery to tissues and organs. People with TDT do not have enough functional hemoglobin in their red blood cells and require regular, lifelong blood transfusions, often beginning early in childhood, along with ongoing iron chelation therapy. While transfusions are necessary for survival, many of the long-term complications of TDT are exacerbated by chronic transfusion therapy and iron overload and cumulative damage to the heart, liver and endocrine system, as well as bone abnormalities and delayed growth and puberty. TDT places a significant and ongoing burden on patients and their families, requiring frequent medical visits and complex lifelong treatment. Despite lifelong treatment, people with TDT in the U.S. face shortened life expectancy, with a median age of death of approximately 37 years, reduced quality of life and productivity, and the estimated lifetime healthcare costs of managing the disease are $5–5.7 million. CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown in clinical trials to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT. In the United States, CASGEVY was approved using the Commissioner’s National Priority Voucher. Vertex has also recently completed regulatory submissions in the Kingdom of Saudi Arabia and United Kingdom to expand the use of CASGEVY to children as young as five. The completed Phase 1/2/3 open-label studies, CLIMB-111 and CLIMB-121, were designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12-35 years with TDT or with SCD and recurrent VOCs. Patients were followed for approximately two years after CASGEVY infusion in these studies. CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs. Enrollment and dosing are complete for the 5–11-year-old cohort in both studies. Each patient in these studies is asked to participate in the ongoing long-term, open-label study, CLIMB-131. CLIMB-131 is designed to evaluate the long-term safety and efficacy of CASGEVY in patients with up to 15 years of follow up after CASGEVY infusion. CASGEVY is indicated for the treatment of patients aged 2 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) and transfusion-dependent ß-thalassemia (TDT). There is potential risk of neutrophil engraftment failure after treatment with CASGEVY. In the clinical trials, all treated patients achieved neutrophil engraftment and no patients received rescue CD34+ cells. Monitor absolute neutrophil counts (ANC) and manage infections according to standard guidelines and medical judgement. In the event of neutrophil engraftment failure, patients should be infused with rescue CD34+ cells.