Exagamglogene autotemcel, sold under the brand name Casgevy, is a

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

used for the treatment of

sickle cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...

and transfusion-dependent

beta thalassemia Beta-thalassemia (β-thalassemia) is an genetic disorder, inherited hemoglobinopathy, blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduce ...

. It was developed by

Vertex Pharmaceuticals Vertex Pharmaceuticals Incorporated is an American biopharmaceutical company based in Boston, Massachusetts. It was one of the first biotech firms to use an explicit strategy of rational drug design rather than combinatorial chemistry. It maint ...

and

CRISPR Therapeutics CRISPR Therapeutics AG is a Swiss–American biotechnology company headquartered in Zug, Switzerland. The company does business as CRISPR Therapeutics, Inc. in the United States. It was one of the first companies formed to utilize the CRISPR gen ...

. The treatment was approved in the United Kingdom for the treatment of sickle cell disease and transfusion-dependent beta thalassemia in November 2023. It was approved in the United States for the treatment of sickle cell disease in December 2023 and for the treatment of transfusion-dependent beta thalassemia in January 2024. Exagamglogene autotemcel is the first cell-based gene therapy treatment utilizing CRISPR/Cas9 gene editing technology to be approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA). The most common side effects include 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.

Medical uses

In the UK, exagamglogene autotemcel is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of transfusion-dependent beta thalassemia and sickle cell disease in patients aged 12 years and older who should be treated with

hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...

but for whom a suitable stem cell donor is not available. In the US, exagamglogene autotemcel is indicated for the treatment of sickle cell disease in people aged 12 years and older with recurrent vaso-occlusive crises, and for the treatment of people with transfusion-dependent beta-thalassemia. The gene therapy is made from the recipient's own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. Prior to treatment, the recipient's own stem cells are collected, and then the recipient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in exagamglogene autotemcel. The modified blood stem cells are transplanted back into the recipient 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.

Side effects

The most common side effects observed in clinical studies included 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.

History

The safety and effectiveness of exagamglogene autotemcel were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent participants with sickle cell disease. Participants had a history of at least two protocol-defined severe vaso-occlusive crises during each of the two years prior to screening. The primary efficacy outcome was freedom from severe vaso-occlusive crisis episodes for at least twelve consecutive months during the 24-month follow-up period. A total of 44 participants were treated with exagamglogene autotemcel. Of the 31 participants with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated participants achieved successful engraftment with no participants experiencing graft failure or

graft rejection Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient ...

. The US

(FDA) granted the application for exagamglogene autotemcel

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

fast track Fast Track, Fast track, or Fasttrack may refer to: Processes and systems * Fast track (FDA), a U.S. Food and Drug Administration expedited review program * Fast track (trade), the authority of the U.S. President to broker trade agreements with lim ...

, and regenerative medicine advanced therapy designations. The FDA granted approval of Casgevy to Vertex Pharmaceuticals.

Society and culture

Legal status

In December 2023, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Casgevy, intended for the treatment of transfusion‑dependent β‑thalassemia and sickle cell disease. As Casgevy is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies. The applicant for this medicinal product is Vertex Pharmaceuticals (Ireland) Limited. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Exagamglogene autotemcel was approved for medical use in the European Union in February 2024.

Economics

The therapy has a US list price of . The cost effectiveness threshold of the therapy in the US is estimated to be between $1.35 million and $2.05 million depending on perspective (healthcare vs limited societal) and assuming the

willingness to pay In behavioral economics, willingness to pay (WTP) is the maximum price at or below which a consumer will definitely buy one unit of a product. This corresponds to the standard economic view of a consumer reservation price. Some researchers, ho ...

for 1

quality-adjusted life year The quality-adjusted life year (QALY) is a generic measure of disease burden, including both the quality and the quantity of life lived. It is used in economic evaluation to assess the value of medical interventions. One QALY equates to one yea ...

(QALY) at $100,000–$150,000. The UK price is estimated to be .

References

External links

* {{DEFAULTSORT:Exagamglogene Autotemcel CRISPR therapy Drugs acting on the blood and blood forming organs Orphan drugs Sickle-cell disease