“I am free of pain and can move after 35 years,” says Victoria Gray, the world’s first sickle cell anaemia patient to recover with a revolutionary gene-editing therapy that won its inventors the Nobel Prize in 2020 and now holds out hope to millions around the world, including India, for a permanent cure.
Gray underwent a clinical trial in 2017 for the drug Casgevy, which uses the innovative gene-editing tool CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and associated protein 9). Given her consistent recovery and the drug’s efficacy in other trial participants, on November 16, the UK became the first country to approve its use for patients of sickle cell anaemia (SCA).
A genetic disease, SCA arises from mutations in haemoglobin-carrying genes, causing red blood cells to assume a crescent shape, potentially obstructing blood flow and leading to severe pain, organ damage, strokes, and other complications. Globally, the current remedy for sickle cell anaemia is limited to bone marrow transplants.
The breakthrough is of particular significance to India, which has the second-highest disease burden of sickle cell anaemia globally after African countries. An estimated 30,000-40,000 children in India are born with the disorder every year. In 2019, a nationwide screening by the Ministry of Tribal Affairs and the Indian Council of Medical Research (ICMR) that covered 1,13,83,664 individuals found the disease to be prevalent in 8.75% of those screened. Latest data shows that one in 86 births among the Scheduled Tribe (ST) population is affected by sickle cell anaemia, with higher rates in central, western and southern India. In her 2023-24 Budget presentation, Finance Minister Nirmala Sitharaman had said that the government aimed to eliminate the disease by 2047.
USA’s Victoria Gray has been battling sickle cell anaemia, a genetic blood disorder, since she was three months old. (Source: Special arrangement)
While Vertex and CRISPR Therapeutics, the manufacturers, have yet to set a price for the gene-editing therapy in the UK, at the moment, in India, it is expected to exceed Rs 1 crore, which could potentially limit access.
The pathbreaking therapy
Speaking to The Indian Express, 38-year-old Gray, a resident of Forest city in Mississippi, US, says she has been battling the genetic blood disorder since she was three months old. Her life was about cramming painkillers and seven hospital visits a year. It was while waiting for a bone marrow transplant that her haematologist recommended CRISPR-Cas9. This basically involves modifying the patient’s DNA, specifically targeting and replacing the faulty haemoglobin gene with a healthy one. To do this, stem cells are taken out of the bone marrow, edited in a laboratory and then infused back into the patient. This restores normal haemoglobin function, offering a potential cure for a lifetime. So Gray can now move about freely and live a normal life. About 29 patients were administered the treatment along with Gray, of whom 28 have no pain and will be followed up for lasting cure. The therapy also works for patients suffering from transfusion-dependent ß-thalassemia.
Sickle Cell Anaemia in India
Announcing UK’s approval of the therapy, Julian Beach, Interim Executive Director of Healthcare Quality and Access at the UK-based Medicines and Healthcare products Regulatory Agency (MHRA), emphasised safety, saying, “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 ß -thalassaemia, relieving the symptoms of disease. We will continue to closely monitor the safety and effectiveness of Casgevy, through real-world safety data and post-authorisation safety studies.”
In the MHRA’s sickle cell trial, 45 patients got Casgevy, but only 29 were eligible for the primary efficacy interim analysis. Among them, 97 per cent were pain crisis-free for at least 12 months post-treatment. In the β-thalassemia trial, 54 received Casgevy, but only 42 were eligible. About 93 per cent didn’t need a blood transfusion for at least 12 months, and three others had more than a 70 per cent reduction in the need for red cell transfusions.
Despite cost, why it’s good news
Back in India, Gautam Dongre, Secretary of the National Alliance of Sickle Cell Organisations (NASCO), feels optimistic despite the likely cost challenges. “Government intervention and subsidies, along with crowdfunding and philanthropy, can enable access to cure. The UK’s approval would inspire Indian researchers to develop their own innovative therapies of CRISPR like they did with CAR-T for blood cancer, ultimately making the treatment more affordable.”
How the technique works
Debojyoti Chakraborty, a molecular biologist at Delhi’s CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), who is being funded by the Department of Science and Technology and the Ministry of Tribal Affairs to conduct a clinical trial on CRISPR-based therapy for sickle cell disease, shares similar optimism. “The regulatory clearance paves the way for replication and broader access in India and work around cost challenges,” he says.
How can costs be reduced? Peter Marks, Director, Center for Biologics Evaluation and Research, US Food and Drug Administration (FDA), feels one can lower developing and manufacturing costs, allowing for more products to enter the market. “This fosters better competition with more efficiency. That’s why we need to standardise the manufacturing process,” he says.
Gray is currently into patient advocacy, campaigning for a wider use and cheaper therapy. Speaking to reporters globally through the US’s National Press Foundation this week, she shared, “The pain would begin in my legs or arms, crawl across my chest to the other arm. It felt like I was struck by lightning as the pain would just bounce all around my body.”
Yet, she completed her education, pursued a nursing degree and birthed three children. But her condition worsened in 2010 as she underwent extensive rehabilitation to regain mobility. “I depended on nursing staff for tasks like bathing, getting dressed and having a meal,” she said.
Awaiting a bone marrow transplant at HCA Healthcare’s Sarah Cannon Research Institute Center and the Children’s Hospital at TriStar Centennial in Nashville, Tennessee, she met Dr Haydar Frangoul. The medical director of paediatric haematology/oncology advised her about CRISPR and she signed up.
Gray underwent blood transfusions and chemotherapy to manage her condition before her gene-edited cells were reintroduced into her body in 2019. “The chemotherapy resulted in mouth sores, hair loss and extreme weakness, necessitating a 30-day isolation period. Upon returning home, I gradually tapered off the strong pain medication I was on — OxyContin, Fentanyl and Dilaudid,” she shared.
After eight months, she became pain-free and now hopes to inspire others. “As long as we don’t give up, we can bring hope to all these countries — India, Nepal, Africa — by speaking up,” she added.
USA's Victoria Gray is the world’s first sickle cell anaemia patient to recover with the revolutionary gene-editing therapy. (Source: Special arrangement) 
USA’s Victoria Gray has been battling sickle cell anaemia, a genetic blood disorder, since she was three months old. (Source: Special arrangement)
Sickle Cell Anaemia in India
How the technique works
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