Sickle Cell Treatment: FDA Approves Gene Therapies for Recurrent Vaso-Occlusive Crises

Highlights:

FDA approves CASGEVY™ and LYFGENIA™, marking a pivotal moment in sickle cell disease treatment
The use of CRISPR technology and gene editing in sickle cell patients – transforming the shape of red blood cells and preventing painful crises
Children’s Hospital of Philadelphia (CHOP) emerges as a qualified treatment center, offering hope to patients with sickle cell disease through innovative gene therapies

Sickle cell treatment enters a transformative era with groundbreaking gene therapies, CASGEVY™ and LYFGENIA™. The Food and Drug Administration (FDA) has given its nod to CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel), marking the inaugural approval of gene therapies for treating sickle cell disease in patients aged 12 and older facing recurrent vaso-occlusive crises (VOCs) ().

Notably, Children’s Hospital of Philadelphia (CHOP), among other sites, played a pivotal role in the rigorous clinical trials leading to this groundbreaking achievement. CHOP stands as a Qualified Treatment Center, offering LYFGENIA manufactured by bluebird bio, and also plans to provide CASGEVY, manufactured by Vertex Pharmaceuticals.

Positive Gene Editing for Sickle Cell Disease and Beta Thalassemia
New approach to gene editing for major blood disorders such as sickle cell disease and beta-thalassemia has been optimized. CRISPR-Cas9 gene editing can edit out diseased genes in blood disorders.

‘A new era in sickle cell treatment! FDA gives the green light to CASGEVY™ and LYFGENIA™ gene therapies, a breakthrough moment in healthcare. #sicklecell #genetherapy ’

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Treatment of Sickle Cell Anemia

"For many years, a bone marrow transplant has been the only transformative option for treating patients with sickle cell disease, and a limited one, as not all patients have a suitable donor," remarked Dr. Alexis A. Thompson, Chief of the Division of Hematology at Children's Hospital of Philadelphia. "Now, after decades of limited progress in treating sickle cell disease, we have reached a historical moment with two new gene therapies."

How Does Acute Pain Crisis in Sickle Cell Disease Arise?
Steps leading to a sickle-cell disease complication that causes acute pain have been explained by MIT researchers.

What is Sickle Cell Anemia?

Sickle cell disease, characterized by deformed blood cells causing blockages in blood vessels, leads to intense pain, strokes, organ damage, and potentially shortened lives.

Increasing Fetal Hemoglobin may be the Key to Help People With Sickle Cell Disease and Thalassemia
An important signaling protein that regulates the production of hemoglobin was discovered. Blocking this protein can increase fetal hemoglobin production and deliver therapeutic benefits to Sickle Cell Disease (SCD) and Beta-Thalassemia.

Newly Approved Gene Therapies for Sickle Cell Anemia

The newly approved gene therapies leverage advanced DNA editing techniques, including CRISPR technology, to enable patients to produce a different form of hemoglobin in their red blood cells, preventing the characteristic crescent shape apparent in sickle cell disease and eliminating pain episodes in almost all patients.

CASGEVY, developed with CRISPR technology, marks a significant milestone as the first FDA-approved therapy utilizing this cutting-edge genetic editing approach. Conversely, LYFGENIA focuses on treating the underlying cause of sickle cell disease by adding a functional gene that enables the production of adult hemoglobin, preventing its crescent-shape formation.

Gene Editing - Potential Treatment for Sickle Cell Disease
Gene editing is a potential treatment for sickle cell disease, states a research presented at the 2018 AAAS Annual Meeting.

Treating Sickle Cell Anemia with Gene Therapy

"In clinical trials with CASGEVY, we have seen the elimination of painful vaso-occlusive crises in more than 90% of patients and a complete elimination of VOC-related hospitalizations in all patients," stated Dr. Stephan A. Grupp, Section Chief of the Cellular Therapy and Transplant Section at CHOP. Dr. Grupp, one of the principal investigators in the clinical trials, emphasized the meaningful impact of the treatment on patients.

"As these therapies become available outside of the landmark clinical trials, we will carefully monitor each patient’s progress," said Dr. Janet Kwiatkowski, Director of the Thalassemia Center at CHOP. "CHOP’s extensive experience in studying and treating patients with these therapies will help ensure we get the best outcomes for these patients."

CHOP's Comprehensive Center for the Cure of Sickle Cell Disease and Other Red Blood Cell Disorders (CuRED) program, established to take the treatment of these disorders beyond supportive care, offers tailored evaluation and cutting-edge treatment. Gene therapy recipients are treated by CHOP’s Cell Therapy and Transplant Section.

"Gene therapy requires specialized centers, and thanks to the work being done in our CuRED Program, CHOP is one such center," stated Dr. Thompson. "The hope is that, as we gain more experience using this technology, more centers will come online, potentially reaching communities worldwide."

CHOP is actively exploring innovative treatments for sickle cell disease, including in vivo modification of blood stem cells and transcriptional regulation of fetal hemoglobin to improve oxygen transfer. As a global leader in cell and gene therapies, CHOP's contributions include FDA-approved therapies such as Kymriah and Luxturna, underscoring its commitment to pushing the boundaries of medical possibilities. The historic FDA approvals for sickle cell disease signal a new era, offering hope for improved patient outcomes and advancements in gene therapy worldwide.

Reference:

FDA Approves Two Gene Therapies for Sickle Cell Disease - (https://www.chop.edu/news/fda-approves-two-gene-therapies-sickle-cell-disease)

Source-Medindia