On Dec. 8, 2023, the U.S. Food and Drug Administration (FDA) approved Bluebird Bio’s Lyfgenia (lovotibeglogene autotemcel) suspension for infusion to treat patients who have sickle cell disease (SCD) with vaso-occlusive events (VOEs), which also are called vaso-occlusive crises (VOCs) or sickle cell crises. It is indicated for patients aged 12 years old and older. It will be administered by healthcare providers trained in its use, who practice in a limited number of facilities that are staffed and equipped to provide comprehensive care for each patient. To make Lyfgenia, CD34+ stem cells are extracted from the patient’s blood and sent to a laboratory, where they are genetically modified with bioengineered non-infective viral vectors. The resulting product is frozen and shipped back to the healthcare facility for a single intravenous (IV) infusion into the patient at a dose of 3 × 10⁶ CD34+ cells/kg or higher. Before the infusion, the patient needs regular blood transfusions to boost hemoglobin counts and chemotherapy (chemo) to suppress the immune system. Afterward, patients must follow standard precautions to lessen the risk of infections for several months or longer. Lyfgenia has a boxed warning that using it has been associated with developing blood cancers for some patients. The launch is planned for early 2024, and the reported cost is $3.1 million. Here is the complete prescribing information.

At a Glance

• Brand (Generic) Name: Lyfgenia (lovotibeglogene autotemcel)
• Manufacturer: Bluebird Bio
• Date Approved: Dec. 8, 2023
• Indication: for treating patients 12 years of age or older who have SCD and a history of VOEs
• Dosage Forms Available: cell suspension containing at least 3 × 10⁶ CD34+ cells/kg for IV infusion
• Launch Date: early in 2024
• Estimated Cost: $3.1 million
• According to the Centers for Disease Control and Prevention (CDC) SCD is the most common hereditary condition in the United States, affecting up to 100,000 American patients.
• Most U.S. patients are of African ancestry, but individuals of southwest Asian, Middle Eastern, Hispanic, or southern European heritage may also have SCD.
• It is a genetic disorder that causes normally pliable, round red blood cells (RBCs) to deform into a characteristic crescent or sickle shape and makes them less flexible. Sickled cells do not survive as long as regular RBCs, so patients who have sickle cell disease have anemia, too. Other complications can include bone pain, delayed growth, infections, kidney disease, low body weight, sores on the legs, and swollen hands and feet.
• The most common complication of sickle cell disease is VOEs, which are caused when small blood vessels are blocked by sickled RBCs in any part of the body. Eventually, internal organs sustain significant damage. Dehydration, extreme heat or cold, illness, and stress can bring about VOEs, which also may happen spontaneously and unpredictably. The intense pain associated with them is the main reason that patients who have sickle disease are hospitalized and/or need emergency room services.
• Using a non-infective virus, Lyfgenia adds working copies of a β-globin gene to the patient’s own hematopoietic stem cells to reduce the number of sickled RBCs.
• Beginning about six months following treatment with Lyfgenia, 94% of patients in a clinical trial had no severe VOEs and 88% had no VOEs.
• In the trial, 20% or more of patients experienced mouth sores and low counts of RBCs and other blood components.
• Since screening for SCD is mandatory at birth, treatment for it begins very early in life.
• Most current drug treatments for SCD only manage its symptoms and complications; they do not affect the underlying causes of the condition. They include antibiotics, blood transfusions, and pain medications. Oral L-glutamate and hydroxyurea products help to prevent VOEs.
• The first drug to treat the cause of SCD, Oxbryta^® (voxelotor – Global Blood Therapeutics) tablets was FDA approved in late 2019. The first sickle hemoglobin polymerization inhibitor, Oxbryta sticks to hemoglobin, attracting more oxygen and stabilizing RBCs. In addition, it may decrease the thickness of blood and the tendency of blood cells to sickle while increasing RBC flexibility. It is taken orally once a day.
• Also in 2019, Adakveo^® (crizanlizumab-tmca – Novartis) was FDA-approved to treat VOEs for patients 16 years of age and older who have SCD. A first-in-class P-selectin inhibitor, Adakveo blocks the activity of a cell adhesion protein involved in VOEs, keeping blood cells from clumping and helping to maintain blood flow. It is administered by a healthcare professional as a 30-minute intravenous (IV) infusion once every four weeks after two loading doses.
• On the same day that Lyfgenia was approved, the FDA also approved Casgevy (exagamglogene autotemcel – Vertex Pharmaceuticals/CRISPR Therapeutics) for treating SCD for patients at least 12 years old. It is the first drug to use CRISPR/Cas9 gene-editing techniques. Also given as one IV dose, Casgevy has similar requirements as Lyfgenia for harvesting the patient’s stem cells and recovering from the infusion.
• With Orphan Drug status, Lyfgenia was granted Fast-Track and Priority Review, as well as Regenerative Medicine Advanced Therapy (RMAT) and Rare Pediatric Disease designations.