The UK has become the first country in the world to approve gene editing as a potential cure for two inherited blood disorders.
The therapy is based on CRISPR gene editing and has been authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) following two global clinical trials, with Imperial College Healthcare NHS Trust leading the UK arm.
The MHRA said the treatment could be used on patients aged 12 and over “after a rigorous assessment of its safety, quality and effectiveness”. The next stage will be a review for cost-effectiveness to see if the treatment can be offered to patients by Britain’s National Health service.
The revolutionary new treatment for sickle-cell disease and transfusion-dependent beta thalassaemia is called Casgevy (exagamglogene autotemcel). It was developed through a partnership between Vertex Pharmaceuticals and CRISPR Therapeutics and is based on the innovative gene-editing tool CRISPR – technology that led its inventors to win a Nobel prize in 2020.
To date, bone marrow transplants, extremely arduous procedures that come with very unpleasant side effects, have been the only long-lasting treatment.
Julian Beach, Interim Executive Director of Healthcare Quality and Access at the MHRA said: “Both sickle cell disease and beta thalassemia are painful, life-long conditions that in some cases can be fatal. To date, a bone marrow transplant – which must come from a closely matched donor and carries a risk of rejection – has been the only permanent treatment option.
“I am pleased to announce that we have authorised an innovative and first-of-its-kind gene-editing treatment called Casgevy, which in trials has been found to restore healthy haemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent beta-thalassaemia, relieving the symptoms of disease. The MHRA 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.
Samarth Kulkarni, chairman and chief executive officer of CRISPR Therapeutics, said: “I hope this represents the first of many applications of this Nobel Prize winning technology to benefit eligible patients with serious diseases.”
Both sickle cell disease and thalassemia are caused by mistakes in the genes that carry hemoglobin, the protein in red blood cells that carry oxygen.
In people with sickle cell — which is particularly common in people with African or Caribbean backgrounds — a genetic mutation causes the cells to become crescent-shaped, which can block blood flow and cause excruciating pain, organ damage, stroke and other problems.
In people with thalassemia, the genetic mutation can cause severe anemia. Patients typically require blood transfusions every few weeks, and injections and medicines for their entire life. Thalassemia predominantly affects people of South Asian, Southeast Asian and Middle Eastern heritage.
The new medicine, Casgevy, works by targeting the problematic gene in a patient’s bone marrow stem cells so that the body can make properly functioning hemoglobin.
Patients first receive a course of chemotherapy, before doctors take stem cells from the patient’s bone marrow and use genetic editing techniques in a laboratory to fix the gene. The cells are then infused back into the patient for a permanent treatment. Patients must be hospitalized at least twice — once for the collection of the stem cells and then to receive the altered cells.
“This is so exciting. It’s a new wave of treatments that we can utilize for patients with sickle cell disease,” said Dr. James LaBelle, director of the pediatric stem cell and cellular therapy program at the University of Chicago. He said Britain’s approval suggested the U.S. authorization was likely “imminent.”
Casgevy is currently being reviewed by the U.S. Food and Drug Administration; the agency is expected to make a decision early next month, before considering another sickle cell gene therapy.
LaBelle said officials at the University of Chicago are “already moving forward to build not only the clinical infrastructure but also the reimbursement infrastructure to get these patients this treatment.”
Britain’s regulator said its decision to authorize the gene therapy for sickle cell disease was based on a study done on 29 patients, of whom 28 reported having no severe pain problems for at least one year after being treated. In the study for thalassemia, 39 out of 42 patients who got the therapy did not need a red blood cell transfusion for at least a year afterwards.
Gene therapy treatments can cost millions of dollars and experts have previously raised concerns that they could remain out of reach for the people who would benefit most.
Last year, Britain approved a gene therapy for a fatal genetic disorder that had a list price of £2.8 million ($3.5 million). England’s National Health Service negotiated a significant confidential discount to make it available to eligible patients.
Vertex Pharmaceuticals said it had not yet established a price for the treatment in Britain and was working with health authorities “to secure reimbursement and access for eligible patients as quickly as possible.”
In the U.S., Vertex has not released a potential price for the therapy, but a report by the nonprofit Institute for Clinical and Economic Review said prices up to around $2 million would be cost-effective.
By comparison, research earlier this year showed medical expenses for current sickle cell treatments, from birth to age 65, add up to about $1.6 million for women and $1.7 million for men.
Millions of people around the world, including about 100,000 in the U.S., have sickle cell disease. It occurs more often among people from places where malaria is or was common, like Africa and India, and is also more common in certain ethnic groups, such as people of African, Middle Eastern and Indian descent.
Scientists believe being a carrier of the sickle cell trait helps protect against severe malaria.
Source: Imperial College London, news agencies.