FDA approves two gene therapies for sickle cell patients, including one that uses CRISPR tech – giving hope to 100,000 Americans with incurable disease

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Written By Maya Cantina
  • Casgevy is the first FDA-approved treatment to use CRISPR gene editing tech
  • Sickle cell disease affects 100,000 Americans, most of whom are Black
  • READ MORE: Humans could be ‘gene-edited’ to fix DNA problems from illnesses

In a ground-breaking decision, the Food and Drug Administration approved the first gene therapies to treat patients with sickle cell disease – a crippling condition that leaves sufferers in life-altering pain.

On Friday, the administration gave the green light to Casgevy and Lyfgenia, for the treatment of sickle cell disease in patients 12 years and older.

Casgevy is the first FDA-approved treatment to use a type of novel gene editing technology called CRISPR. Lyfgenia uses conventional gene therapy – not gene editing – to treat the condition.

Sickle cell disease is the umbrella term for a group of inherited conditions that severely impact the shape and function of red blood cells. It affects 100,000 Americans and 15,000 Brits, most of whom are Black.

These therapies could bring hope to the tens of thousands of Americans with the condition, which was only approved to be treated by a bone marrow transplant, an invasive procedure most patients do not qualify for.

Dr Reshma Kewalramani, CEO and president of Vertex Pharmaceuticals, one of the companies behind Casgevy, said: ‘CASGEVY’s approval by the FDA is momentous: it is the first CRISPR-based gene-editing therapy to be approved in the US.’

However, while the news brings hope to sickle cell patients, there are concerns in the medical community that the therapies will be hard to access because of the anticipated high cost and limited hospitals able to administer them 

Sickle cell disease patients, of which there are around 100,000 in the US, do not make hemoglobin properly — a substance in red blood cells, which carry oxygen around the body. As a result, their red blood cells become rigid and shaped like a crescent (pictured) instead of a disc, which can cause them to die and become stuck in blood vessels

Casgevy, made by Boston-based Vertex Pharmaceuticals (pictured) and Crispr Therapeutics in Switzerland, works by editing the faulty HBB gene behind both conditions in a patient's bone marrow stem cells so the body produces functioning hemoglobin

Casgevy, made by Boston-based Vertex Pharmaceuticals (pictured) and Crispr Therapeutics in Switzerland, works by editing the faulty HBB gene behind both conditions in a patient’s bone marrow stem cells so the body produces functioning hemoglobin

In a healthy person, red blood cells – produced by stem cells within bone marrow – are round, concaved discs that can bend and flex easily.

However, in people with sickle cell disease, faulty stem cells produce red blood cells that are crescent-shaped. These cells are rigid, unable to squeeze through smaller blood vessels and prone to causing blockages that deprive parts of the body of oxygen, leading to immense pain and organ damage.

Until now, a bone marrow transplant was the only approved treatment for the condition. A transplant is a procedure in which healthy blood-forming stem cells are transplanted from a healthy donor to replace bone marrow in the patient that is not producing enough healthy cells.

How does Casgevy work?

Casgevy, made by Boston-based Vertex Pharmaceuticals and Crispr Therapeutics in Switzerland, works by editing the faulty HBB gene behind both conditions in a patient’s bone marrow stem cells so that the body produces functioning hemoglobin.

To do this, stem cells are taken out of a patient’s bone marrow and edited in a laboratory using molecular ‘scissors’, which precisely disable the faulty gene.

Stem cells are then infused back into the patient, who may need to spend a month or longer in the hospital while the treated cells start to make healthy red blood cells. 

The results have the potential to be life-long. 

An ongoing trial of the drug so far shows that 97 percent of sickle cell patients were free from severe pain for at least one year after treatment.

In a separate study for β-thalassaemia, 93 percent of participants did not need a blood transfusion for at least one year. Among those who did, their need for transfusions fell by 70 percent. 

Side effects included nausea, fatigue, fever and increased risk of infection.

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Stem cells are the body’s ‘raw materials,’ or cells that are able to develop into many different specialized cell types. They can be used to fix damaged tissues, and researchers believe stem-cell therapies may one day be able to treat conditions like Alzheimer’s disease and paralysis.

In most cases of a bone marrow transplant, the donor is a sibling, but even a sibling only has a one-in-four chance of being a match for the patient. And, often transplants are not performed due to the risks, which include the transplanted cells attacking other cells in the recipient’s body, which can be life-threatening.

More than 30 FDA-approved gene therapies are used to treat several different cancers and the blood disorder hemophilia. However, many are largely inaccessible due to high costs.

Casgevy was recently approved in the UK to treat sickle cell and transfusion-dependent β-thalassemia – a shortage of red blood cells that leads to severe anemia. It’s expected to cost the UK government approximately $1.25 million (£1million) per patient.

Made by Boston-based Vertex Pharmaceuticals and Crispr Therapeutics in Switzerland, Casgevy is the first medicine to be licensed that uses the innovative gene-editing tool CRISPR. This process is known as ‘genetic scissors’ that enables scientists to make precise changes to DNA. Its inventors were awarded the Nobel Prize in 2020.

The therapy works by editing the faulty HBB gene, which causes sickle cell disease in a patient’s bone marrow stem cells, so the body can produce properly functioning hemoglobin, the protein in red blood cells responsible for delivering oxygen to tissues throughout the body.

To do this, stem cells are taken out of a patient’s bone marrow and edited in a lab using molecular ‘scissors,’ which precisely disable the faulty gene.

Stem cells are then infused back into the patient, who may need to spend a month or longer in the hospital while the treated cells start to make healthy red blood cells.

Scientists believe the results have the potential to be lifelong.

An ongoing trial of the drug so far shows 97 percent of sickle cell patients were free from severe pain for at least one year after treatment.

Dr Kewalramani added: ‘As importantly, Casgevy is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease.

‘I want to convey my deepest gratitude to the patients and investigators whose trust in this program paved the way for this landmark approval.’

ᴀʀᴛɪᴄʟᴇ ꜱᴏᴜʀᴄᴇ

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