Vertex Nets Early Casgevy Approval for Transfusion-Dependent Thalassemia


The therapy’s original PDUFA date was March 30, 2024, but the TDT approval followed only a month after exa-cel's sickle cell approval.

The FDA has approved Vertex Pharma and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel; Casgevy) for the treatment of patients 12 years and older with transfusion-dependent beta thalassemia (TDT), over 2 months before the scheduled March Prescription Drug User Fee Act (PDUFA) date.

“Today’s approval is an important step in the advancement of an additional treatment option for individuals with beta-thalassemia, a debilitating disease that places individuals at risk of many serious health problems,” said Nicole Verdun, MD, director, Office of Therapeutic Product, Center for Biologics Evaluation and Research, FDA, said in an FDA statement.2 “The approval of a cell-based gene therapy for this condition using CRISPR/Cas9 technology reflects FDA’s continued commitment to supporting safe and effective treatments that leverage the most promising and cutting-edge medical technologies.”

Exa-cel is the first approved CRISPR/Cas9 gene-edited cell therapy in the US, first netting an approval for for the treatment of severe sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises in December 2023. It was approved alongside bluebird bio's lovotibeglogene autotemcel (lovo-cel), marketed as Lyfgenia.3

“Thalassemia is an inherited disorder wherein the patients require regular blood transfusions, every 2-6 weeks, depending upon the severity of their disease, for their entire lives. In high resource settings, these blood transfusions are a burden and while they are resource intensive, most patients can be managed easily. These autologous genetic therapies provide a way to potentially reduce or eliminate that transfusion burden and associated side effects. Patients would then not have to go to their hematologist every few weeks, which would be remarkable,” Akshay Sharma, MBBS, a bone marrow transplant physician at St. Jude Children’s Research Hospital, told CGTLive about the approval.

READ MORE: MHRA Approves First CRISPR-Based Therapy Exa-cel for Sickle Cell and Transfusion-Dependent β-Thalassemia

"But I am most excited about the potential of these therapies to change the lives of patients in low resource settings where these blood transfusions are essentially a lifeline, and not easily accessible. If one time gene therapies can be implemented in Southeast Asia – where the burden of thalassemia is probably the highest in the world, and where blood transfusion supply is not consistent – that in my opinion would be a game changer for these patients. These one-time autologous genetic therapies are not only desired but are urgently needed in such areas and we must do better for their equitable distribution outside North America and Europe," Sharma continued.

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.

“On the heels of the historic FDA approval of CASGEVY for sickle cell disease, it is exciting to now secure approval for TDT well ahead of the PDUFA date,” Reshma Kewalramani, MD, Chief Executive Officer and President, Vertex, said in a statement.1 “TDT patients deserve new, potentially curative treatment options, and we look forward to bringing CASGEVY to eligible patients who are waiting.”

"Individuals with TDT have a tremendous treatment burden and are at risk of health problems related to their necessary blood transfusions and iron chelation treatments," Janet Kwiatkowski, MD, MSCE, the director of the Thalassemia Center at Children's Hospital of Philadelphia, told CGTLive. "As a clinician and investigator in the clinical trial that led to the approval of Casgevy, I am excited that the FDA has approved this treatment, which now offers another potentially curative treatment option."

1. Vertex Announces US FDA Approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia. News release. January 16, 2024.
2. FDA Roundup: January 16, 2024. News release. January 16, 2024.
3. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. News release. FDA. December 7, 2023. Accessed December 7, 2023.
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