The US Food and Drug Administration on Tuesday approved Bluebird Bio’s gene therapy for a rare inherited blood disease. The therapy, known as Zynteglo, will be the first commercial product in the United States for the Somerville-based company. The one-time treatment comes with $2.8 million price that makes it the most expensive drug on the market here.
Bluebird won approval for Zynteglo in Europe in 2019 but eventually shuttered its commercial operations there when payers refused to cover its previous $1.8 million price tag.
The therapy treats the severe form of a disease called beta thalassemia, where a genetic mutation in the beta-globin gene impairs the ability of blood cells to carry oxygen throughout the body. People with the condition require regular blood transfusions once or twice a month, and chelation therapies to reduce high levels of iron caused by the transfusions.
Zynteglo could change that by providing a healthy copy of the essential beta-globin gene to blood stem cells, allowing their bodies to make healthy blood cells and eliminate the need for regular transfusions. In clinical trials, about 90 percent of patients who got the one-time therapy no longer needed transfusions to treat their disease.
Dr. David A. Williams, chief of hematology/oncology at Boston Children’s Hospital, was impressed with the effectiveness of the therapy. “This is clearly very clinically meaningful for the patients,” he said.
Before Zynteglo’s approval, stem cell transplants were the only potentially curative options for people with beta thalassemia, but many people with the condition are unable to find a genetically-matched donor. Doctors who treat people with the condition were excited by the approval of Zynteglo.
“This is really huge. The idea that now you have the option of a curative therapy for all patients is enormous,” said Dr. Sujit Sheth, chief of the division of pediatric hematology/oncology at Weill Cornell Medicine.
Sheth noted that stem cell transplants carry the risk of immune rejection, which can be deadly. “You have a far lower risk of complications from getting your own cells back than if you’re getting it from someone else,” he said.
Bluebird estimates that there are as many as 1,500 people with transfusion-dependent beta thalassemia in the United States. Thomas Klima, the firm’s chief commercial officer, told the Globe that as many as 850 of them may qualify for Zynteglo.
The firm expects about one-third of those patients to be “pretty eager” to get therapy, Klima added. Another third may need “more information and time” to think it over, and the final third may consider their current transfusion treatments fine.
Despite the relatively modest numbers of patients who may get the therapy, the approval is a major win for Bluebird, which has faced a series of troubles over the past few years that brought its stock falling about 98 percent from its peak in 2018. The firm said it would lay off 30 percent of its employees in April and warned investors it only had enough cash to last until the first half of 2023.
“Over the last year we faced so many challenges,” Klima said. “But the group that’s here now — and the group that’s getting ready to launch our gene therapies — couldn’t be more thrilled.”
The therapy is made from a patient’s own blood stem cells collected during a hospital visit and shipped to the contract manufacturing firm Lonza, just south of Houston, TX. Once there, scientists will treat the cells with Bluebird’s gene therapy, made from a lentivirus that shuttles the beta-globin gene into the cells.
After a quality check, cells are shipped back to the hospital. Before getting the altered cells infused, a patient must undergo chemotherapy to clear out space in their bone marrow for the new cells to engraft. Once they take hold, they will make new healthy red blood cells for years, potentially indefinitely.
Craig Butler, national executive director of the Cooley’s Anemia Foundation — a nonprofit patient organization for thalassemia — is excited for people to have an alternative to time-consuming transfusions.
“It’s usually a full day process for someone, which means that they’re missing a day of work or a day of school,” he said. The approval of Zynteglo “means that they will no longer have to be bound to transfusions for the rest of their lives.”
Wanda Sihanath, 26, was one of the first people to get the therapy in a clinical trial in 2014. She hasn’t needed a transfusion in over eight years. “It feels like really great not to be tethered to hospital and having to check in at least once a month,” she said.
Sihanath, who lives in San Jose, was excited to hear that Zynteglo is approved. “I am super stoked,” she said, and is hopeful that the therapy will help untether people from regular hospital visits.
But the chemotherapy Sihanath got to prepare her body for the gene therapy may have affected her fertility, and she wishes she would have sought “a little more counseling” about getting the procedure at a young age. Doctors say that some young people may wish to hold off on getting the therapy.
The therapy will only be offered at a small number of centers across the United States, including at Boston Children’s Hospital.
Colleen Dansereau, the hospital’s director of clinical operations of the gene therapy program, anticipates that the hospital will be ready to start the treatment procedure for a patient by September. But she anticipates it could take longer for Bluebird to get ready and for insurers to guarantee payment for the therapy.
Boston Children’s regularly provides transfusions for about 45 people with the condition, plus additional patients referred from other centers, Dansereau said.
The hospital may end up treating additional patients with beta thalassemia from other parts of the world where the disease is more prevalent, including the Middle East and Southeast Asia, Dansereau added. “We anticipate that we could have an increase in our international services for this particular product.”
Zynteglo is the third gene therapy approved by the FDA. The Roche gene therapy Luxturna, which treats a genetic eye disease, was approved in 2017 with a price tag of $850,000. The Novartis gene therapy Zolgensma, which treats spinal muscular atrophy, was approved in 2019 with a cost of $2.1 million. The FDA could approve a fourth gene therapy, also made by Bluebird, in September.
Ryan Cross can be reached at firstname.lastname@example.org. Follow him on Twitter @RLCscienceboss.