Vertex Pharmaceuticals and CRISPR Therapeutics have made a groundbreaking announcement regarding the conditional marketing authorization granted by the United Kingdom (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA) for CASGEVY™ (exagamglogene autotemcel [exa-cel]), a remarkable CRISPR/Cas9 gene-edited therapy designed to address sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).

This authorization signifies a pivotal moment in the realm of science and medicine, marking the inaugural regulatory approval of a CRISPR-based therapeutic globally. Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex, remarked, "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." Such a milestone could herald a new era of potential applications for this Nobel Prize-winning technology in the treatment of severe diseases.

CASGEVY has been granted approval for treating eligible patients aged 12 and above with SCD who experience recurrent vaso-occlusive crises (VOCs) or TDT, provided they lack a human leukocyte antigen (HLA) matched related hematopoietic stem cell donor. Approximately 2,000 individuals in the U.K. fall within the eligible patient population for CASGEVY.

Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics, expressed hope that this approval marks the beginning of a broader trend in utilizing CRISPR technology for the benefit of individuals grappling with serious illnesses.

Clinical trials for CASGEVY, spanning the globe and focusing on SCD and TDT, achieved their primary objectives by enabling patients to become free from severe VOCs or attain transfusion independence for a minimum of 12 consecutive months. Furthermore, these benefits are expected to be long-lasting once attained. Notably, the safety profile observed in the 97 SCD and TDT patients treated with CASGEVY thus far in these ongoing studies has generally aligned with myeloablative conditioning using busulfan and hematopoietic stem cell transplant.

Professor 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 Haematologist at Imperial College Healthcare NHS Trust, expressed enthusiasm about this authorization's potential to offer a new therapeutic option for eligible patients eagerly awaiting innovative treatments. Vertex has already commenced close collaboration with national health authorities in the U.K. to expedite access for eligible patients.

Sickle cell disease (SCD) is an inherited blood disorder with debilitating consequences, causing severe pain, organ damage, and a shortened lifespan due to misshapen or "sickled" blood cells. Individuals with SCD can experience excruciating blood vessel blockages, known as vaso-occlusive crises (VOCs), leading to acute chest syndrome, stroke, jaundice, and symptoms of heart failure. Anemia is also prevalent among SCD patients, resulting in end-organ damage and premature death. The hallmark of SCD, VOCs, frequently leads to severe and incapacitating pain. Presently, standard treatment options for SCD primarily address symptoms and do not fully alleviate the disease's burden, necessitating chronic care. The only existing cure involves a stem cell transplant from a matched donor, an option available to only a small fraction of individuals with SCD. Consequently, SCD necessitates lifelong treatment, consuming substantial healthcare resources and culminating in reduced life expectancy and productivity. In the U.K., the average age of death for individuals with SCD is approximately 40.

Beta thalassemia, on the other hand, is an inherited blood disorder affecting red blood cells, causing anemia and resulting in symptoms such as fatigue and shortness of breath. Infants with beta thalassemia may experience failure to thrive, jaundice, and feeding difficulties. Complications of beta thalassemia may include an enlarged spleen, liver, and heart, misshapen bones, and delayed puberty. Treatment is personalized based on the severity of the disease, often involving regular blood transfusions that can lead to iron buildup and necessitate numerous hospital visits. While stem cell transplant from a matched donor offers a cure, it remains accessible to only a small fraction of individuals with beta thalassemia. Consequently, beta thalassemia entails lifelong treatment, substantial healthcare resource utilization, and ultimately results in reduced life expectancy, diminished quality of life, and decreased lifetime earnings and productivity. In the U.K., the average age of death for individuals with TDT is approximately 55.

CASGEVY™ (exagamglogene autotemcel [exa-cel]) is a genetically modified autologous CD34+ cell enriched population containing human hematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 at the erythroid-specific enhancer region of the BCL11A gene.

The latest data from pivotal trials, which are still ongoing, were presented at the European Hematology Association Congress in June 2023.

Exa-cel is currently under review by the European Medicines Agency, the Saudi Food and Drug Authority, and the U.S. Food and Drug Administration (FDA). The FDA has assigned Priority Review for SCD and Standard Review for TDT, with target action dates set for December 8, 2023, and March 30, 2024, respectively.