Casgevy for Sickle Cell Disease: The World’s First Gene Therapy Approved in UK

UK has approved, Casgevy, the world’s first gene therapy for sickle cell disease. Sickle cell disease is a result of a single mutation in the hemoglobin chain.

Patients with sickle cell disease have abnormally shaped red blood cells (sickle-like cells). These cells, unlike the biconcave disc-shaped red cells, can not pass through smaller capillaries.

Thus, patients with sickle cell disease often develop vaso-occlusive crises manifesting as bone crises, acute chest syndrome, and hemolytic crises.

The treatment of sickle cell disease, until very recently, was only symptomatic. These included blood transfusion, hydration, hydroxyurea, and pain management.

Lately, the FDA approved other drugs for treating the sickle cell crisis. These include [Ref]:

• Endari (L-glutamine oral powder):

It was approved in 2017 for children 5 years of age and above to lower sickle cell-associated complications such as acute chest syndrome.

• Crizanlizumab:

It was approved in 2019 for adults with sickle cell disease who had a vaso-occlusive crisis.

It is a P-selectin inhibitor that prevents vessel occlusion by inhibiting the binding of red cells to the endothelium.

In clinical trials, it lowered the incidence of hospitalization due to vaso-occlusive crisis by 45%.

• Voxelotor:

It was approved in 2019 for children and adolescents who were 12 years of age or older.

It prevents the polymerization of HbS and increases oxygen affinity for hemoglobin.

However, the only curative treatment is hematopoietic stem cell transplantation.

“Casgevy is a gene therapy that may be close to a cure as this treatment not only might prevent vaso-occlusive crises but may also prevent the need for blood transfusion”

Casgevy for Sickle Cell Disease: Key Points

• Sickle cell disease & β-thalassemia are genetic disorders arising from errors in the genes responsible for producing hemoglobin, crucial for oxygen transport in red blood cells.
• Casgevy, a new treatment for sickle-cell disease and β-thalassemia got the green light from the Medicines and Healthcare Products Regulatory Agency (MHRA).
• The treatment was created by the Boston-based pharmaceutical company Vertex Pharmaceuticals and the biotech company CRISPR Therapeutics in Zug, Switzerland.
• Casgevy functions by modifying the faulty gene in a patient’s bone marrow stem cells, enabling the production of healthy hemoglobin. The process includes taking stem cells from the bone marrow, making edits in a laboratory, and subsequently reintroducing the modified cells back into the patient.

UK Approved Casgevy for Sickle Cell Disease!

Sickle cell anemia deeply affects individuals both physically and emotionally [ref]. This inherited blood disorder causes red blood cells to assume a rigid, crescent-like shape, hindering their ability to flow smoothly through blood vessels.

But this condition does not stop there, it affects a person’s daily life and weakens physical endurance while emotionally training the patient [ref].

Furthermore, the impact extends beyond the patient, affecting families and communities as they navigate the challenges associated with managing and supporting those with sickle cell anemia.

Effective treatment for sickle cell anemia is crucial to alleviate the persistent pain, as of 2021, there are over 8 million people affected by this condition worldwide [ref].

However, there are insufficient resources for its cure, and bone marrow transplants are rarely done, considering the risks involved.

The Medicines and Healthcare Products Regulatory Agency (MHRA) has approved a novel treatment targeting sickle-cell disease and transfusion-dependent β-thalassemia in patients aged 12 and above [ref].

This authorization follows a thorough evaluation of the treatment’s safety, quality, and effectiveness.

‘I am pleased to announce that we have authorized an innovative and first-of-its-kind gene-editing treatment called Casgevy, which in trials has been found to restore healthy hemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent β -thalassemia, relieving the symptoms of disease’ stated Julian Beach, Interim Executive Director of Healthcare Quality and Access at the MHRA.

This latest technical advancement is important and can be life-saving once it is authorized on a global level.

Casgevy (exagamglogene autotemcel) Mechanism of Action:

It operates as a groundbreaking treatment for sickle-cell disease and β-thalassemia by utilizing the revolutionary gene-editing tool CRISPR–Cas9 [ref].

In individuals with these genetic disorders, errors in the genes responsible for hemoglobin lead to abnormal red blood cells and associated health complications.

Casgevy’s process involves extracting stem cells from the patient’s bone marrow and employing CRISPR–Cas9 to edit specific genes, with a focus on disrupting the BCL11A gene.

This gene normally inhibits the production of fetal hemoglobin, and by cutting both strands of its DNA, Casgevy enables the production of fetal hemoglobin, which lacks the abnormalities associated with the conditions.

After the gene-editing process, the modified stem cells, now capable of producing fetal hemoglobin, are reintroduced into the patient’s body.

This infusion is preceded by a treatment to prepare the bone marrow to receive the edited cells.

Once inside the body, these stem cells give rise to red blood cells containing the stable form of hemoglobin, alleviating symptoms by enhancing the oxygen supply to tissues.

While the process may necessitate patients spending some time in a hospital facility to allow the edited cells to establish themselves in the bone marrow, it holds promise for transforming the management of sickle-cell disease and β-thalassemia.

Is Casgevy Gene Therapy Safe?

Beach also said, ‘ The MHRA will continue to closely monitor the safety and effectiveness of Casgevy, through real-world safety data and post-authorization safety studies being carried out by the manufacturer’.

Those in the ongoing trials experienced side effects like nausea, fatigue, fever, and a higher risk of infection.

However, there were no major safety concerns, The MHRA and the manufacturer are keeping a close eye on the technology’s safety and will share more results later.

The 29 out of 45 patients who received Casgevy were eligible for primary efficacy interim analysis. And only 28 faced no pain for 12 months after the initial treatment [ref].

Further research needs to be performed on a larger sample size as well. Till then, this treatment is deemed safe and is significantly less painful than a bone marrow transplant.

Cost of Casgevy for Sickle Cell Disease:

Even though it is an incredible achievement, its price point is what will decide who can benefit from its effects.

The United Kingdom is yet to decide how much Casgevy will cost, but there is a rough estimate that it will cost 2 million USD in The States.

Such expensive costs can become a hindrance for a lot of people looking to save their lives from this debilitating condition.

How is Casgevy Administered?

Casgevy is given by taking cells from a person’s bone marrow, changing a gene in these cells in a lab, and then putting these modified cells back into the person.

Before that, the bone marrow gets ready with a treatment. As stated above, after the procedure, patients might spend at least a month in the hospital as the treated cells settle in the bone marrow and start making healthy red blood cells.