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In a big first, Vertex Pharmaceuticals and CRISPR Therapeutics announced today that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization for Casgevy (exagamglogene autotemcel [exa-cel]) for the treatment of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). Casgevy is a CRISPR/Cas9 gene editing therapy.

“Today is a historic day in science and medicine: this authorization of Casgevy in Great Britain is the first regulatory authorization of a CRISPR-based therapy in the world,” said Reshma Kewalramani, MD, CEO and president of Vertex.

Casgevy has been authorized for the treatment of patients 12 years of age and older with SCD with recurrent vaso-occlusive crises (VOCs) or TDT, for whom a human leukocyte antigen (HLA) matched related hematopoietic stem cell donor is not available. There are an estimated 2,000 patients eligible for the treatment in the U.K.

“I hope this represents the first of many applications of this Nobel Prize winning technology to benefit eligible patients with serious diseases,” said Samarth Kulkarni, PhD, chairman and CEO of CRISPR Therapeutics.

Two global clinical trials of Casgevy in SCD and TDT met their respective primary outcome of patients becoming free from severe VOCs or transfusion independent for at least 12 consecutive months.

Once achieved, these benefits are potentially expected to be life-long. The safety profile of 97 SCD and TDT patients treated to date with Casgevy in these ongoing studies is generally consistent with myeloablative conditioning with busulfan and hematopoietic stem cell transplant. The latest data from the ongoing pivotal trials was presented at the European Hematology Association Congress in June 2023.

“This authorization offers a new option for eligible patients who are waiting for innovative therapies, and I look forward to patients having access to this therapy as quickly as possible,” said Josu de la Fuente, principal investigator in the CLIMB-111 and CLIMB-121 studies, professor of practice (Cellular & Gene Therapy) at Imperial College London, and consultant hematologist at Imperial College Healthcare NHS Trust.

SCD is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. It causes severe pain, organ damage and shortened lifespan due to misshapen or “sickled” blood cells. The only cure for SCD today is a stem cell transplant from a matched donor, but this option is only available to a small fraction of patients.

Beta thalassemia is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. A lack of red blood cells, also known as anemia, is the primary manifestation of beta thalassemia. Because of this anemia, people living with beta thalassemia may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems.

Casgevy is a genetically modified autologous CD34+ cell enriched population that contains human hematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 at the erythroid-specific enhancer region of the BCL11A gene.

Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. 

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