Vertex and CRISPR Therapeutics Announce MHRA Marketing Authorisation Application Validation for CRISPR/Cas9 Gene-Edited Therapy

Vertex Pharmaceuticals (Europe) and CRISPR Therapeutics (NASDAQ: CRSP) have announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has validated the Marketing Authorisation Application (MAA) of exa-cel for the treatment of sickle cell disease (SCD) and transfusion dependent beta thalassaemia (TDT) in Great Britain. The submission is supported by two global Phase 3 studies investigating exa-cel as a potential one-time therapy for people with SCD or TDT.

“Today marks a significant milestone in our efforts to bring a new one-time therapy to people living with sickle cell disease or transfusion-dependent beta thalassaemia,” said Nia Tatsis Ph.D., Executive Vice President, Chief Regulatory and Quality Officer. “We look forward to working with the MHRA on our application, the first for a CRISPR-based therapy for a genetic disease.”

Vertex has requested Orphan Drug Designation as part of the MAA.

Exagamglogene autotemcel (exa-cel)

Exa-cel, formerly known as CTX001™, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with SCD or TDT, in which a patient’s own hematopoietic stem cells are edited to produce high levels of foetal haemoglobin (HbF; haemoglobin F) in red blood cells. HbF is the form of the oxygen carrying haemoglobin that is naturally present during foetal development, which then switches to the adult form of haemoglobin after birth. The elevation of HbF by exa-cel has the potential to reduce or eliminate painful and debilitating vaso-occlusive crises (VOCs) for patients with SCD and alleviate transfusion requirements for patients with TDT. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021 and presented at the European Hematology Association Congress in June 2022.

CLIMB-111 and CLIMB-121

The ongoing Phase 1/2/3 open-label trials, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 12 to 35 years with TDT or with SCD, respectively. The trials are now closed for enrollment.

Sickle Cell Disease

Sickle cell disease (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. SCD causes severe pain, organ damage and shortened life span due to misshapen or “sickled” blood cells. People with SCD experience several complications in addition to pain crises, including strokes and anaemia. People with SCD often have spleen damage, which puts them at risk for bacterial infections. Most often, treatment is focused on relieving pain and minimising organ damage, requiring medication and sometimes monthly blood transfusions and frequent hospital visits. The only cure for SCD today are stem cell transplants, but these options are only available to a small fraction of people living with SCD. SCD requires a lifetime of treatment and can result in a reduced life expectancy.

Transfusion-Dependent Beta Thalassaemia

Transfusion-dependent beta thalassaemia (TDT) 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, known as anemia, is the primary manifestation of TDT. Because of this anemia, people living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart complications; misshapen bones; and delayed puberty. People with TDT need regular blood transfusions to deliver healthy donated blood to their body. This requires many hospital visits and can also lead to an unhealthy buildup of iron. The amount and frequency of blood transfusions is personalised and depends on the severity of disease each person experiences. The only cure for TDT today are stem cell transplants, but these options are only available to a small fraction of people living with TDT. TDT requires a lifetime of treatment and can result in a reduced life expectancy.

Vertex and CRISPR Collaboration

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. Exa-cel represents the first potential treatment to emerge from the joint research programme. Under an amended collaboration agreement, Vertex now leads global development, manufacturing and commercialisation of exa-cel and splits programme costs and profits worldwide 60/40 with CRISPR Therapeutics.