The FDA has approved Casgevy (exagamglogene autotemcel; exa-cel), a CRISPR/Cas9 gene-edited cell therapy produced by Vertex Pharmaceuticals, for the treatment of transfusion-dependent beta thalassemia (TDT) in patients twelve years and older. This approval comes two months ahead of the March 30, 2024, Prescription Drug User Fee Act (PDUFA) date.
The single dose therapy is an ex vivo application requiring the removal of bone marrow stem cells from the patient. Gene-editing is then completed outside the body before reinfusing those cells back to the patient. Since the administration of Casgevy requires experience in stem cell transportation, “Vertex is establishing a network of independently operated, authorized treatment centers (ATCs) throughout the US to offer CASGEVY to patients. All nine ATCs activated in the US are able to offer CASGEVY to eligible patients with TDT and sickle cell disease (SCD). Additional ATCs will be activated in the coming weeks and a complete list of ATCs can be accessed at CASGEVY.com.”(1)
The nine activated ATCs are as follows:
Boston Medical Center, Boston, Massachusetts
Children's National Hospital, Washington, Washington DC
City of Hope National Medical Center, Duarte, California
Medical City Dallas Hospital, Dallas, Texas
Methodist Hospital, San Antonio, Texas
Nationwide Children's Hospital, Columbus, Ohio
Ohio State University Wexner Medical Center, Columbus, Ohio
The Children’s Hospital at TriStar Centennial, Nashville, Tennessee
University of Chicago, Chicago, Illinois
Vertex states there are about 1,000 TDT patients in the US twelve years of age and older are that may be eligible for this one-time treatment:
TDT is a serious, life-threatening genetic disease. TDT requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones, and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In the US, the median age of death for patients living with TDT is 37 years. Stem cell transplant from a matched donor is a curative option but is only available to a small fraction of people living with TDT because of the lack of available donors.(2)
The approval is based on data from the phase 1/2/3 CLIMB-111 clinical trial (NCT03655678) in patients with TDT and the phase 3 long-term follow-up study CLIMB-131 (NCT04208529), which includes both patients with SCD and patients with TDT. In CLIMB-111, 39 of 42 evaluable patients (93%) were free of the need for a red blood cell (RBC) transfusion for 12 months or more posttreatment. Furthermore, the 3 patients who did not achieve this end point demonstrated a greater than 70% decrease in necessitation of RBC transfusions. The adverse event (AE) profile of exa-cel during the trial was similar to that of autologous stem cell transplant with AEs such as nausea, fatigue, fever, and increased risk of infection.(3)
The reported list price for Casgevy for both Sickle Cell and Transfusion Dependent Thalassemia is $2.2 million.(4)
Currently there are two gene therapies, Casgevy and Lyfgenia, for the treatment of transfusion dependent thalassemia; and two gene therapies, Casgevy and Zynteglo, for the treatment of Sickle Cell Disease in patients ages twelve and up.
Article by Kathy Clark, RN, BSN, CMCN, Vice President, Director of Managed Care. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. The following sources were used as reference material for this article:
1. Vertex Announces US FDA Approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia. News release. January 16, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-us-fda-approval-casgevytm-exagamglogene
2. FDA Roundup: January 16, 2024. News release. January 16, 2024. https://www.fda.gov/news-events/press-announcements/fda-roundup-january-16-2024
3. CGT Live. Johnson, V. Vertex Nets Early Casgevy Approval for Transfusion-Dependent Thalassemia. Accessed January 16, 2024. https://www.cgtlive.com/view/vertex-nets-early-casgevy-exa-cel-approval-transfusion-dependent-thalassemia
4. Pharmaphorum: First CRISPR drug Casgevy gets swift second approval. Accessed January 17, 2024. https://pharmaphorum.com/news/first-crispr-drug-casgevy-gets-swift-second-approval#:~:text=Vertex%20and%20CRISPR%20say%20they,for%20both%20TDT%20and%20SCD.