Gene therapy is a treatment that replaces defective genes with healthy ones, adds new genes to help the body fight or treat disease, or edits genes that can then correct disease caused by other genes. Gene therapy works by altering the genetic code to recover the functions of proteins that are critical to how the body works. It can also be used to train the body’s immune system to recognize and attack cancer cells.

Gene therapy is a one-time treatment that can help people living with challenging diseases.

Conditions We Treat

Sickle cell disease: An inherited blood disorder characterized by an abnormal type of hemoglobin, a protein inside red blood cells, which carry oxygen.

Beta thalassemia major: An inherited blood disorder that affects the production of the beta globin protein, a type of protein in red blood cells, which carry oxygen.

Treatment Process

The treatment process our gene therapy team uses is known as gene addition. With gene addition, we can treat diseases at the genetic level by adding genetic material to a patient’s cells to compensate for a missing or faulty gene. A functional gene is introduced into cells ex vivo—the cells are modified outside the body—and then the modified cells are infused back into the patient.

A number of steps are involved in the treatment process:

1. The patient’s stem cells are removed from the bloodstream via a catheter placed into a vein.
2. The desired genetic material is inserted into the stem cells. A vector—a vehicle designed to deliver therapeutic genetic material directly into a cell—is used in the manufacturing process.
3. The patient is admitted to the hospital and receives chemotherapy to eliminate abnormal cells and make space for the new stem cells.
4. The stem cells with the newly inserted genetic material are returned to the patient’s bloodstream via an intravenous catheter.
5. The new cells go to the bone marrow and make healthy blood cells.

Gene Therapy Products We Use

• Lyfgenia™ (lovotibeglogene autotemcel) for Sickle Cell Disease
  
  Lyfgenia is a gene addition therapy that adds functional copies of the beta-globin gene to the patient’s own blood stem cells. This leads to production of anti-sickling hemoglobin that may decrease or stop vaso-occlusive events.
  
  The safety and effectiveness of Lyfgenia are based on the analysis of data from a 24-month multicenter study in patients with sickle cell disease and a history of vaso-occlusive events between the ages of 12 and 50 years.
  
  Eighty-eight percent of patients enrolled in the study experienced complete resolution of vaso-occlusive events between 6 and 18 months after infusion with Lyfgenia.
  
  Side effects included mouth sores and low levels of platelets, white blood cells, and red blood cells—all consistent with chemotherapy and underlying disease. Patients treated with Lyfgenia receive lifelong monitoring for blood cancer, which has developed in some patients.

• Zynteglo™ (betibeglogene autotemcel) for Transfusion-Dependent Beta Thalassemia Major
  
  Zynteglo is a gene addition therapy that adds functional copies of the beta-globin gene to the patient’s own blood stem cells. This leads to production of sufficient hemoglobin so the patient does not need to receive regular red blood cell transfusions.
  
  The safety and effectiveness of Zynteglo are based on data from Phase 3 studies—HGB-207 (Northstar-2) and HGB-212 (Northstar-3)—and the long-term follow-up study LTF-303.
  
  The 24-month phase 3 studies of Zynteglo included patients aged 4 to 34 years with both non-β0/β0 and β0/β0 genotypes. The longest follow up was four years. Eighty-nine percent of patients across ages and genotypes achieved transfusion independence—they no longer needed red blood cell transfusions for at least 12 months while maintaining an average total hemoglobin of at least nine g/dL.
  
  Adverse reactions included mucositis, neutropenia (low count of neutrophils, a type of white blood cell), nausea, abdominal pain, musculoskeletal pain, headaches, diarrhea, constipation, and decreased appetite. Some patients experienced complications related to low counts of platelets, white blood cells, and red blood cells. 
   
• Casgevy™ (exagamglogene autotemcel) for Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia Major
  
  Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ blood stem cells are modified by genome editing using CRISPR/Cas9 technology.
  
  CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.
  
  The safety and effectiveness of Casgevy were evaluated in a multi-center trial in adult and adolescent patients with sickle cell disease. Patients had a history of at least two protocol-defined severe vaso-occlusive events during each of the two years prior to screening. The primary efficacy outcome was freedom from severe vaso-occlusive events for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment; no patients experienced graft failure or graft rejection. 
  
  The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching.