Hope for sickle cell disease patients as gene therapy gets more approvals

After years of exploration on gene therapy for sickle cell disease (SCD) and transfusion-dependent β-thalassemia, there is, finally, a glimmer of hope for patients suffering from this ailment associated with inherited red blood disorders after the FDA approved new treatment. (1)

The FDA announced in early December 2023 the approval of the use of Casgevy (exagamglogene autotemcel) treatment for patients 12 years and older with recurrent acute pain crisis using a gene-editing technology, CRISPR/Cas9.

Through the Casgevy therapy, a patient with SCD will have stem cells taken out of the bone marrow and the gene in the cells edited in a laboratory before they are infused back into the same bone marrow.

With the approval of Casgevy, an estimated one in every 365 children, who are said to be born with SCD are expected to benefit from this durable one-time administered therapy.

SCD causing cells are abnormal crescent- or “sickle”-shaped because of a genetic mutation and hence have limited or no capacity to bend or move leading to blockage of the flow of blood to the rest of the body, subsequently triggering health challenges such as stroke, eye problems, infections, and acute pain crises.

Casgevy, which has been developed out of collaboration between Swiss-American biotechnology company, CRISPR Therapeutics and American biopharmaceutical firm Vertex Pharmaceuticals Inc had previously been approved in some other countries for some eligible patients with SCD or transfusion-dependent beta thalassemia.

For instance, the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) had approved the use of Casgevy, the first-of-its-kind gene-editing treatment, after trials showed it can “restore healthy haemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent β -thalassaemia, relieving the symptoms of disease.” (2)

However, the MHRA said even with the authorization of the gene therapy, the Agency “will continue to closely monitor the safety and effectiveness of Casgevy, through real-world safety data and post-authorisation safety studies being carried out by the manufacturer.”

In Europe, Vertex was in January 2020 granted orphan designation by the European Commission of the active substance ‘autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene’ for the treatment of SCD.

Under the FDA approval, Vertex would be the manufacturer and exclusive license holder of Casgevy as well as the Casgevy™ word mark and design.

FDA has also approved Lyfgenia™ (lovotibeglogene autotemcel), also known as lovo-cel, for the treatment of SCD in patients who 12 years and older. (3)

Like Casgevy, Lyfgenia is a one-time gene therapy with potential to ease acute pain crisis and “is custom-designed to treat the underlying cause of sickle cell disease.” (3)

The treatment pioneered by US biotechnology company, Bluebird Bio Inc, works by adding a functional β-globin gene to patients’ own hematopoietic (blood) stem cells.

Other SCD treatments that have previously been approved include Oxbryta (voxelotor), the first and only direct hemoglobin S (HbS) polymerization inhibitor taken orally once a day for SCD patients.

The European Medicines Agency (EMA) had previously recommended granting a marketing authorisation, within the European Union, of Oxbryta for the treatment of excessive breakdown of red blood cells, also known as haemolytic anaemia, due to SCD in patients 12 years of age and older. (4)

Oxbryta was, however, granted the drug accelerated approval by the FDA in September 2023. The accelerated approval allows for earlier approval of pharmaceutical products for the treatment of serious conditions and fill an unmet medical need. (5)

Oxbryta, which has been developed by US biopharmaceutical company, Global Blood Therapeutics, comes with capability to block sickle hemoglobin clumping together, hence leading to SCD.

It is estimated 250 million people globally carry the sickle cell disease causing gene and other hemoglobin diseases while approximately 300,000 infants are born with a haemoglobin disease worldwide. (6)

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REFERENCES;

1.   https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

2.   https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia

3.   https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-fda-approval-lyfgeniatm-lovotibeglogene

4.   https://www.ema.europa.eu/en/news/new-treatment-sickle-cell-disease

5. https://www.scdfc.org/news/3qtvixe147hy7yn6o677e1bti63cct

6.   https://www.scdfc.org/news/blog-post-title-three-w6l6x