Pharmaceutical Executive Editorial Staff

Vertex Pharmaceuticals' and CRISPR Therapeutics’ Cas9 therapy Casgevy approved as a one-time treatment for transfusion-dependent beta thalassemia on the heels of its approval last month for sickle cell disease.

The FDA has granted another approval to Vertex Pharmaceuticals' and CRISPR Therapeutics’ gene-editing therapy Casgevy (exagamglogene autotemcel [exa-cel]) as a one-time treatment for transfusion-dependent beta thalassemia (TDT) in patients 12 years of age and older.1 Last month, Casgevy became the first FDA-approved novel genome editing technology for sickle cell disease (SCD), which was a significant advancement in gene therapy. The latest approval was months ahead of the FDA’s assigned Prescription Drug User Fee Act (PDUFA) date.

“We are pleased with the approval of Casgevy in TDT well ahead of the PDUFA date,” said Samarth Kulkarni, PhD, chairman and chief executive officer of CRISPR Therapeutics.2 “The approval is a reflection of the power and versatility of the CRISPR platform to bring a potentially curative treatment option to patients suffering from this devastating disease.”

Because treatment with Casgevy involves stem cell transplantation, Vertex is working develop a network of independent authorized treatment centers (ATCs) in addition to nine existing ATCs in the United States to administer Casgevy to eligible patients with TDT and SCD.

“On the heels of the historic FDA approval of Casgevy for sickle cell disease, it is exciting to now secure approval for TDT well ahead of the PDUFA date,” said Reshma Kewalramani, MD, chief executive officer and president of Vertex, said in a press release.1 “TDT patients deserve new, potentially curative treatment options, and we look forward to bringing Casgevy to eligible patients who are waiting.”

Casgevy is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy. The treatment involves editing a patient’s own hematopoietic stem and progenitor cells at the erythroid specific enhancer region of the BCL11A gene via a precise double-strand break. This process produces elevated levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells, which is the form of the oxygen-carrying hemoglobin found naturally during fetal development. HbF transforms to the adult form of hemoglobin following birth.

In clinical trials, Casgevy was found to lower or eliminate vaso-occlusive crisis (VOCs) for patients with SCD and transfusion requirements for patients with TDT, according to Vertex.

TDT is a life-threatening genetic condition that has a significant impact on health-related quality of life scores compared with the general population. Lifetime healthcare costs for patients with TDT in the United States are estimated to run up $5.7 million.1 Treatment of the disease involves regular blood transfusions and iron chelation therapy.
Because of the effects of anemia, patients with TDT may have fatigue and shortness of breath, whereas infants may develop failure to thrive, jaundice, and feeding problems. Potential comorbidities of TDT include an enlarged spleen, liver, and heart; misshapen bones, and delayed puberty.

Because treatment of the disease lasts throughout a patient’s lifespan and uses significant healthcare resources, patients with TDT may have lower life expectancy, reduced quality of life, and decreased lifetime earnings and productivity. The median age of death for US patients with TDT is 37 years.

Although a stem cell transplant from a matched donor may cure the condition, it is only available to a small proportion of patients with TDT because there is a limited number of available donors.1 The list price of Casgevy for TDT has yet to be released; however, the cost for the treatment in SCD is $2.2 million.