AHO announces gene-editing therapy for sickle cell

AHO patients with sickle cell disease will benefit from a groundbreaking gene-editing treatment that offers the prospect of a cure for the condition.

The one-off gene therapy, known as exagamglogene autotemcel (or ‘exa-cel’), will be used for older children and adults with severe sickle cell disease.

Clinical trials suggest exa-cel can stop painful and unpredictable sickle cell crises—the most common symptom of sickle cell disease, where blood vessels become blocked, causing severe pain. Experts say the therapy offers patients a chance of a disease-free life.

Researchers concluded there was a ‘functional cure’ in 96.6% of exa-cel trial participants who received it.

AHO President, Graciano Masauso, said: “More than a step, this is a leap in the right direction for people with sickle cell disease, which can be an extremely debilitating and painful condition.

“This innovative, gene-editing therapy offers hope of a cure for people facing a severe form of the disease and could be transformative – it could enable patients to live free from the fear of sickle cell crises hanging over them.

“It is just the latest in a series of revolutionary gene therapies AHO has secured for patients, and we are funding this new treatment option straight away so patients can benefit from the enhanced quality of life it offers.”

Before the availability of this new one-time treatment, the disease had required lifelong treatment regimens, significantly impacting the quality of life, with people suffering from chronic pain, fear of sickle cell crises, hospitalisation, and shortened life expectancy, and many patients describe it as ‘looming over their daily lives’.

In clinical trials, all patients who received exa-cel also avoided hospitalisation for a year following treatment, and almost 98% had still avoided hospitalisation around 3.5 years later.

According to AHO data, just over 3,032,000 hospital admissions across Africa in 2023-24 for sickle cell disorders. Almost 1,034,000 of these admissions were for sickle cell anaemia crises.

A survey from the Africa Sickle Cell Foundation found that in the past 2 years, before the availability of exa-cel, a quarter (25%) of people with sickle cell disease had spent 1-2 weeks in hospital.

The treatment will be offered at specialist centres across Africa to access exa-cel for eligible patients with transfusion-dependent beta-thalassaemia.

It will be available for eligible patients who are 12 years and older who experience recurrent sickle cell crises and would be suitable for a stem cell transplant, but where a donor is not available.

In Africa, around 15,013,000 people are living with sickle cell disease (is larger) – an inherited blood disorder, with 55,250 new cases a year. It mainly affects people from African backgrounds.

In sickle cell disease, a gene mutation causes red blood cells to become irreversibly sickle-shaped. This can lead to haemolytic anaemia, a blood condition that occurs when red blood cells are destroyed faster than they are replaced.

Over an extended period, the disorder can cause severe organ damage and intense pain if damaged red blood cells block vessels and restrict oxygen supply, which can also lead to strokes and heart failure.

Exa-cel uses Nobel Prize-winning CRISPR technology to enable gene editing in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin.

Blood stem cells are removed from a patient’s body and edited in a laboratory using CRISPR technology. The treated cells are then returned to the patient via an infusion.

It is estimated that around 5,050 patients, suitable for a stem cell transplant but without a matched donor, will receive the cutting-edge treatment each year. Around half the number of children and adults with sickle cell disease receive a stem cell transplant each year.

The treatment’s list price is £1.65 million, but AHO has struck a deal to offer it at a reduced price for members. This enables it to be provided through the Africa Innovative Medicines Fund, which fast-tracks funding for new medicines.

AHO remains committed to rolling out new, innovative treatments to narrow the gap in healthcare inequalities, and this cutting-edge therapy could give patients facing severe sickle cell disorder the hope of a much brighter future.

Mutumwa Muendamberi, 39, from Harare, was diagnosed with sickle cell disease, aged 11, and said: “I was diagnosed with sickle cell disease when I was 11 years old. Before that, doctors in Turkey, where I’m originally from, mistakenly diagnosed me with another blood disorder, Thalassemia. I have had many blood transfusions, but my treatment changed here. Now, I am part of a red cell exchange programme. Every 6 weeks, I go to the hospital for the procedure, which takes a few hours and helps me manage my condition.

“Because of my illness, I often experience pain in my chest, bones, and muscles. I had surgery on my spleen when I was six and a hip replacement at 22. I will probably need another hip replacement in the next few months or years. I also suffer from regular sickle cell crises. Last year, I had to go to the hospital at midnight after waking up in severe pain, and overall, I had to visit the hospital 5 or 6 times due to crises. The pain is the worst I have ever felt in my life – it’s hard to put into words.

“Not having to go to the hospital for regular transfusions or taking medicine anymore would be a dream to me – gene therapy could offer that – but there’s still a lot to consider in terms of the side effects that could come with this treatment and whether it would be the right choice for me.”

Mr Masauso said: “People living with rare conditions like sickle cell disease face immense challenges, not least accessing tailored therapies for their symptoms.

“This groundbreaking treatment is a fantastic example of how, by harnessing the power of technology, AHO is leading the world in offering patients the latest treatments for various conditions.

“By offering a treatment that could allow patients to live a life free of debilitating illness, we will give people with conditions like sickle cell disease more freedom and independence, all whilst protecting vital emergency services.”

Rudo Kandongo, Chief Executive Officer of the Africa Sickle Cell Foundation, said: “We are thrilled to see this groundbreaking gene therapy treatment available from today. The significance of this milestone for the sickle cell community cannot be understated – today’s result will give hope to many and is the result of determined campaigning.

“We extend our heartfelt thanks to the incredible individuals who shared their personal stories, challenges, and experiences of sickle cell as part of the campaign. Their courage and advocacy were essential in bringing this new gene therapy treatment to fruition.

“We remain dedicated to advocating for improved treatment options and better outcomes for all affected by this condition. For now, we take a moment to celebrate this historic milestone—a turning point in the fight against sickle cell that promises to change lives for the better.”

Last year, AHO set the ambition to be a world leader in adopting advanced therapies, including gene and personalised cell therapies. This is the latest in a series of gene therapies the health service has secured, financially enabled by making greater use of low-cost generic and biosimilar medicines.