FDA approves world-first gene editing treatment: Sickle cell therapy gives hope to 100,000 Americans with incurable disease – but it’ll cost millions of dollars per DOSE

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Written By Rivera Claudia

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  • 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 people 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, most of whom are Black.

These newly approved therapies could bring hope to 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 gene behind sickle cell disease 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 gene behind sickle cell disease in a patient’s bone marrow stem cells so the body produces functioning hemoglobin

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 their expensive prices. 

Casgevy’s genome editing technology has been approved to treat sickle cell patients with recurrent vaso-occlusive crises – a complication of the condition that occurs when sickled red blood cells block blood flow so severely tissues become deprived of oxygen. 

Approximately 16,000 patients experience this sickle cell ‘flare-up.’

However, because of the advanced technology of Casgevy, Vertex said it ‘requires specialized experience in stem cell transplantation’ and only a handful of hospitals have been authorized to administer the treatment.

The company has partnered with hospitals in Boston, Los Angeles, Dallas and San Antonio, Texas, Columbus, Ohio, Chicago, Nashville and Washington, DC, and it plans to engage with more facilities in the coming weeks. 

Another hurdle to accessing the treatment: its expected multi-million dollar price tag. 

Casgevy, co-developed with Switzerland-based Crispr Therapeutics, was recently approved in the UK to treat sickle cell, but it is expected to cost the UK government approximately £1million ($1.25million) per patient.

Nevertheless, the FDA’s approval of Casgevy means for the first time, patients could have access to a one-time therapy that offers the potential to cure their condition, Dr Kewalramani said.

The gene therapy uses the innovative gene-editing tool CRISPR, which is the process 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, so the body can produce properly functioning hemoglobin.

To do this, stem cells are taken out of a patient’s bone marrow and edited in a lab using the ‘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 Samarth Kulkarni, chairman and CEO of CRISPR Therapeutics, called Casgevy ‘transformative.’

The CEO added: ‘This approval of the first-ever medicine using CRISPR gene editing is breathtaking.’ 

Unlike Casgevy, Lyfgenia, developed by Bluebird Bio, uses solely gene therapy. It has been approved to treat patients 12 years and older with sickle cell disease and a history of vaso-occlusive events. 

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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With this one-time treatment, a patient’s blood stem cells are genetically modified to produce gene-therapy made hemoglobin, the protein in red blood cells responsible for delivering oxygen throughout the body, that functions as the normal hemoglobin in healthy people. 

Blood cells containing the healthy hemoglobin have a lower risk of sickling and blocking blood flow. 

After modification, the stem cells are then delivered to the sickle cell patient.

Dr Julie Kanter, an investigator working on Lyfgenia, also called the therapy ‘transformative’ 

And Regina Hartfield, president and CEO of the Sickle Cell Disease Association of America Inc., said it could change the lives of people and families affected by sickle cell disease.’

In a person without sickle cell disease, red blood cells – produced by stem cells within bone marrow – are round, concaved discs that can bend and flex easily.

However, in people with the condition, 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.

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.

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