CRISPR FDA approved treatment of Sickle Cell Anemia

Extracted Attributes

• Award

  Best Science Breakthrough (2023 Bestie Awards)

• Mechanism

  Editing the BCL11A gene in hematopoietic stem cells to increase fetal hemoglobin (HbF) production

• Technology

  CRISPR/Cas9 genome editing

• Therapy Name

  Casgevy (exagamglogene autotemcel)

• Target Condition

  Sickle Cell Disease (SCD)

• Eligible Patients

  12 years and older with recurrent vaso-occlusive crises

• FDA Approval Date

  2023-12-08

• Estimated U.S. Patient Reach

  16,000 to 20,000 individuals

Timeline

• James B. Herrick provides the first medical description of sickle cell disease. (Source: Wikipedia)

  1910-01-01

• E. A. Beet and J. V. Neel determine the genetic transmission of sickle cell disease. (Source: Wikipedia)

  1949-01-01

• Carriers of the abnormal gene are found to be protected against malaria, explaining its persistence in certain populations. (Source: Wikipedia)

  1954-01-01

• The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee meets to discuss the application for exagamglogene autotemcel. (Source: Web Search)

  2023-10-31

• The FDA officially approves Casgevy as the first CRISPR-based gene therapy in the U.S. (Source: Web Search)

  2023-12-08

• The All-In Podcast names the CRISPR treatment for sickle cell anemia as the Best Science Breakthrough of 2023. (Source: 47c5a1f9-3bf9-4d68-ae85-a92717b28f78)

  2023-12-31

Sickle cell disease

Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to the red blood cells adopting an abnormal sickle-like shape under certain circumstances. With this shape, they are unable to deform as they pass through capillaries, causing blockages. Problems in sickle cell disease typically begin around 5 to 6 months of age. Several health problems may develop, such as attacks of pain (known as a sickle cell crisis) in joints, anemia, swelling in the hands and feet, bacterial infections, dizziness and stroke. The probability of severe symptoms, including long-term pain, increases with age. Without treatment, people with sickle cell disease rarely reach adulthood, but with good healthcare, median life expectancy is between 58 and 66 years. All of the major organs are affected by sickle cell disease. The liver, heart, kidneys, lungs, gallbladder, eyes, bones, and joints can be damaged from the abnormal functions of the sickle cells and their inability to effectively flow through the small blood vessels. Sickle cell disease occurs when a person inherits two abnormal copies of the β-globin gene that make haemoglobin, one from each parent. The abnormal gene generates haemoglobin S (HbS) which changes the properties of red blood cells. A sickle cell crisis occurs when red blood cells switch from the normal saucer-like shape to a sickle-like shape which can obstruct small blood vessels; an attack can be set off by temperature changes, stress, dehydration, and high altitude. A person with a single abnormal gene does not usually have symptoms and is said to have sickle cell trait, these people are also referred to as carriers. Diagnosis is by a blood test, and some countries test all babies at birth for the disease. Diagnosis of the unborn foetus is also possible during pregnancy. The care of people with sickle cell disease may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain medication. Other measures may include blood transfusion and the medication hydroxycarbamide (hydroxyurea). In 2023, new gene therapies were approved involving the genetic modification and replacement of blood forming stem cells in the bone marrow. As of 2021, sickle cell disease is estimated to affect about 7.7 million people worldwide, directly causing an estimated 34,000 annual deaths and a contributory factor to a further 376,000 deaths. About 80% of sickle cell disease cases are believed to occur in sub-Saharan Africa. It also occurs to a lesser degree among people in parts of India, Southern Europe, West Asia, North Africa and among people of African origin (sub-Saharan) living in other parts of the world. The condition was first described in the medical literature by American physician James B. Herrick in 1910. In 1949, its genetic transmission was determined by E. A. Beet and J. V. Neel. In 1954, it was established that carriers of the abnormal gene are protected to some degree against malaria, which accounts for its persistence in populations threatened by malaria.

Web Search Results

• Vertex and CRISPR Therapeutics Announce US FDA Approval of ...

  Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (Nasdaq: CRSP) announced today that the U.S. Food and Drug Administration (FDA) has approved CASGEVY™ (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 genome-edited cell therapy, for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises (VOCs). This approval means that for the first time, approximately 16,000 patients with SCD may be eligible for a durable [...] “CASGEVY’s approval by the FDA is momentous: it is the first CRISPR-based gene-editing therapy to be approved in the U.S. As importantly, CASGEVY is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “I want to convey my deepest gratitude to the patients and investigators whose trust in this program paved the way for this [...] stem cell transplant from a matched donor, but this option is only available to a small fraction of patients living with SCD because of the lack of available donors.

• Revolutionary breakthrough: FDA approves CASGEVY, the first ...

  Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting from a β-globin chain mutation that causes abnormal hemoglobin (HbS) polymerization and leads to severe complications. Current treatment options primarily focus on symptom management, with limited curative potential. Recently, Casgevy, the first CRISPR/Cas9-based gene therapy for SCD, has received breakthrough FDA approval. Clinical trials have shown that Casgevy administered to patients aged older than or equal to 12 years [...] revolutionized genome editing techniques, opening avenues for its potential application in clinical settings. Casgevy stands as the first FDA-approved therapeutic application of CRISPR/Cas9, a revolutionary genome editing technology, designed for addressing SCD in patients aged 12 years and above, as well as in individuals experiencing recurrent vaso-occlusive crises.26. Through the administration of Casgevy, hematopoietic stem cells undergo precise modifications via the CRISPR/Cas9 [...] In essence, CRISPR/Cas9, exemplified by Casgevy, represents a pivotal advancement in SCD treatment. The findings from clinical trials, particularly targeting the erythroid-specific enhancer region of the BCL11A gene, have unveiled a promising future. The precise genetic modifications induced by Casgevy resulted in elevated HbF levels and a significant reduction in vaso-occlusive events. This revolutionary approach not only obviates the need for recurrent transfusions but promises a remarkable

• FDA Approves First Gene Therapies to Treat Patients with Sickle ...

  Today, the U.S. Food and Drug Administration approved two milestone treatments, Casgevy and Lyfgenia, representing the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older. Additionally, one of these therapies, Casgevy, is the first FDA-approved treatment to utilize a type of novel genome editing technology, signaling an innovative advancement in the field of gene therapy. [...] Casgevy, a cell-based gene therapy, is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (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.

• FDA Approves Two Gene Therapies for Sickle Cell Disease

  In a transformative moment for patients with sickle cell disease, and after rigorous clinical trials that took place at Children’s Hospital of Philadelphia (CHOP) and other sites, the Food and Drug Administration (FDA) has approved CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel), the first two gene therapies for the treatment of sickle cell disease in patients 12 years and older with recurrent vaso-occlusive crises (VOCs). CHOP is a Qualified Treatment Center [...] In a transformative moment for patients with sickle cell disease, and after rigorous clinical trials that took place at Children’s Hospital of Philadelphia (CHOP) and other sites, the Food and Drug Administration (FDA) has approved CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel), the first two gene therapies for the treatment of sickle cell disease in patients 12 years and older with recurrent vaso-occlusive crises (VOCs). CHOP is a Qualified Treatment Center [...] Researchers have been extensively studying the use of gene therapy and CRISPR technology to edit portions of DNA in people with inherited or genetic disorders, like sickle cell disease. In the case of sickle cell disease, the newly approved therapy edits DNA within the patient’s own cells and enables the patient to produce a different form of hemoglobin in their red blood cells. Clinical trials at CHOP and other sites have shown that successful gene-editing can prevent cells from taking on the

• CRISPR Therapeutics Announces Completion of FDA…

  If approved, exa-cel could be the first genetic therapy available to approximately twenty thousand people with severe SCD in the U.S. The FDA granted priority review for exa-cel in the treatment of people with SCD and assigned a Prescription Drug User Fee Act (PDUFA) action date of December 8, 2023. Exa-cel’s Biologics License Application (BLA) for transfusion-dependent beta-thalassemia (TDT) was assigned a PDUFA date of March 30, 2024. [...] ZUG, Switzerland and BOSTON, Oct. 31, 2023 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP) today announced the completion of the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee meeting for exagamglogene autotemcel (exa-cel) for the treatment of SCD in people ages 12 and older with recurrent vaso-occlusive crises (VOCs). Exa-cel is the first potential therapy to emerge from a strategic partnership between CRISPR Therapeutics and Vertex [...] This press release may contain a number of “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding CRISPR Therapeutics’ expectations about any or all of the following: (i) exa-cel’s potential for approval in TDT and SCD, including accelerated approval for SCD in the U.S., as well as the timing of any such approval by the FDA and that exa-cel could be the first genetic therapy available to eligible