The Food and Drug Administration’s approval Friday of two innovative gene therapy treatments for sickle cell anemia has brought a rare moment of hope and celebration to people with this agonizing blood disorder.
But there is no clear path to the new therapies (unique treatments so effective in clinical trials that they have been hailed as cures) to reach the countries where the vast majority of people with sickle cell anemia live. Shortly after approval, its manufacturers announced sticker prices in the millions of dollars: 3.1 million dollars for Lyfgenia, made by Bluebird Bio, and 2.2 million dollars for Casgevy, manufactured by Vertex Pharmaceuticals.
Lyfgenia will launch in the United States. Vertex has been prioritize winning approval in six rich countries (the United States, Italy, Great Britain, France, Germany and Saudi Arabia) that, for an estimateThey are home to 2 percent of the world’s sickle cell population.
Three quarters of the world’s sickle cell anemia patients are in sub-Saharan Africa. Several million of them are believed to be sick enough to be eligible for the new therapies, compared with about 20,000 in the United States.
Many African patients have closely followed online news about the success of treatments in clinical trials. In Tanzania, information about Casgevy spread a few months ago through a WhatsApp group that Shani Mgaraganza created for mothers of children with sickle cell anemia. Her son Ramadhani, 12, and her daughter Nasra, 10, suffer from this inherited disorder, which causes episodes of stabbing pain and damages their organs. She said the therapy seemed like a miracle.
“Everyone was saying, ‘Thank God our kids are going to be okay,’” he said.
Then the mothers learned what it would probably cost. “It would be billions of Tanzanian shillings,” Mgaraganza said. “No one can afford this. “It was demoralizing.”
The issue of access is a priority for Jennifer Doudna, a scientist at the University of California, Berkeley, who shared the Nobel Prize in Chemistry for pioneering the gene-editing method, CRISPR, that underpins Casgevy. “It won’t be widely available today,” she said. “Now that we have this approval, we really need to figure out how we’re going to open it up to more people.”
Two key factors put it out of reach for patients in Africa.
First, the price: The treatments are too expensive for governments struggling to pay for basic health services. In some cases, there may be substantial additional costs, such as a patient’s prolonged stay in hospital for gene therapy.
The second barrier is the medical infrastructure: administering treatment is a process that lasts months in medical centers that can perform stem cell transplants. Patients must have cells harvested and flown to a lab for manufacturing, undergo grueling chemotherapy and endure a long hospital stay.
“A drug that requires so many resources may not be appropriate in many places where the amount of healthcare resources is more limited,” said Vertex chief scientific officer Dr. David Altshuler.
He said the company was working to develop cheaper and easier approaches to treating sickle cell patients around the world, including a simple pill, which has not yet been tested in humans. “This has been going on for a long time and I feel like we’re at the beginning of the next phase,” she said.
A spokesperson for Bluebird Bio, Jess Rowlands, said it was “the unfortunate reality” that the infrastructure needed for such gene therapies “does not exist in much of the world”. Bluebird “will continue to invest in approaches that can support global access in the future,” she said.
New drugs often debut in rich countries years before reaching the poorest areas of the world. The disparities have been exacerbated in recent years, as a wave of cutting-edge therapies with eye-popping prices have transformed the lives of patients in wealthy countries. Vertex in particular has faced criticism for keeping its pioneering cystic fibrosis drugs out of the reach of thousands of patients in low-income countries.
Manufacturers charge high prices even when it is clear that low-income countries cannot afford to pay those costs to protect their ability to demand higher prices in places like the United States and Europe.
Dr. Obiageli Nnodu, director of a sickle cell program at the University of Abuja in Nigeria, has discussed the new gene therapy with some of her patients. It’s a source of joy, she said, “but it’s just one step away.”
The mutation that causes sickle cell anemia is believed to have emerged 7,000 years ago in West Africa. (Around the world, the majority of people who suffer from the disease are of African descent.) It became more common in places where malaria was endemic because a single copy of the gene protects against malaria infection. But two copies of the gene cause red blood cells to deform into a sickle shape that can block blood vessels, causing excruciating pain, strokes and other life-shortening problems.
Casgevy modifies patients’ DNA to correct the underlying cause of their disease. In a clinical trial, she eliminated pain attacks during 29 of 31 patients with sickle cells.
Questions about access extend to the United States, where many people with the disease are poor and live in states that have not expanded their Medicaid programs.
Those who can receive Casgevy in the United States and other high-income countries will go to accredited medical centers to perform stem cell transplants. almost 200 Clinical programs in eight countries (the vast majority in the United States and none in Africa) have received that seal of approval from the Foundation for the Accreditation of Cellular Therapy, a U.S.-based group that reviews hospitals.
Patient cells collected at those hospitals will be flown to a manufacturing facility in the United States or Europe. There, scientists will use the CRISPR-Cas9 gene editing system to disable a key gene. This is the first approved therapy using CRISPR.
That complex and expensive process is a far cry from the level of care available to most African sickle cell patients today.
Few African countries even routinely screen newborns for sickle cell, something that is standard in rich countries. If undiagnosed, those children miss out on a crucial penicillin treatment that can prevent the pneumonia that often kills sickle cell patients as babies. In Nigeria, It is estimated that up to half of children with sickle cell anemia die before his fifth birthday.
Beyond that, many don’t have access to a medication called hydroxyurea that keeps red blood cells round and reduces episodes of severe pain. That drug costs about $7 per patient per month in Nigeria, which still keeps it out of reach for many families, Dr. Nnodu said. Many of his patients have difficulty paying for even basic painkillers like folic acid and pain relievers, he said.
Until new gene therapies, the only cure for sickle cell anemia was a bone marrow transplant, in which patients have their stem cells removed and replaced with healthy cells from a donor who does not have sickle cells. The procedure is reserved only for the most serious cases because it does not always work and is risky; that kills 5 to 20 percent of those who suffer from it, depending on age.
Several medical centers in sub-Saharan Africa have recently begun performing bone marrow transplants for patients with sickle cell anemia, but only a handful of wealthy African patients can afford it.
In Dodoma, Tanzania’s capital, Benjamin Mkapa Hospital has performed five transplants so far, with the government footing the bill of about $50,000 per patient. Dr. Stella Malangahe, a hematologist there, said her patients often ask her when the hospital will start offering gene therapy. She has no answer.
A small but growing number of African patients are traveling to India for bone marrow transplants, where they are cheaper and hospitals have more experience performing them. Fortis Memorial Research Institute in Gurugram, outside New Delhi, has performed such transplants on nearly 100 African patients with sickle cell anemia, according to Dr. Vikas Dua, head of pediatric hematology.
Mgaraganza, the Tanzanian mother who works at a bank in Dar es Salaam, temporarily moved her family to India in September so her two children could receive transplants there. She donated her healthy stem cells and the children underwent chemotherapy and were infused with the new cells. The final bill for two transplants could be $80,000, and she is still figuring out how to come up with the money.
The children are struggling with the side effects of the transplant medications. Mgaraganza would have preferred them to receive gene therapy, which she learned about by watching YouTube videos. But his children couldn’t wait until someone found a way to bring him to Africa, she said.
Nkem Azinge, a government project manager in Abuja, Nigeria, has been saving money to pay for a bone marrow transplant in India. At 34 years old, he knows that he is a decade away from the average life expectancy of a Nigerian sickle cell patient, and that each pain crisis he suffers further damages his organs. Now, he is debating whether to suspend his plan in India and instead try to find a way to get gene therapy abroad.
“If I had the opportunity to do this, I would do it because I live with unimaginable pain,” he said.
Beyond industry, other research groups, including the National Institutes of Health and Dr. Doudna’s Berkeley’s Innovative Genomics Institute is developing techniques that would make a gene therapy for sickle cells cheaper and easier to administer. But experts warn that these approaches have not yet been proven to work and are still many years away from being implemented.
The patient population in Africa with sickle cell anemia will continue to grow as screening and access to basic interventions expand and fewer children die in infancy. That will increase the chances that two people with the sickle cell genetic trait will have a child who may have the inherited disease.
Dr. Léon Tshilolo treats patients with sickle cell anemia at a hospital in Kinshasa, the capital of the Democratic Republic of the Congo. Some struggle to raise even $7 each month for basic medications; two have traveled abroad to receive bone marrow transplants. Increasingly, people are asking about gene therapies.
“My young patients, teenagers, have the Internet,” he said, “and they say, ‘Doctor, I saw that some people who have this are being completely cured. When will this arrive in Kinshasa?’”
