It was a late Friday night for Bluebird Bio as the company awaited the Food and Drug Administration’s approval of its gene therapy for a rare and lethal brain disease in children. The one-time therapy, Skysona, will be sold for $3 million, making it the most expensive drug in the country.
On Monday, the Somerville firm was basking in the sorely needed positive news. In a call with investors, chief executive Andrew Obenshain called the approval a “landmark moment” for the company and for families with children afflicted with the disease.
“To have reached this moment after a decade of research and development, with many setbacks along the way, is truly remarkable,” Obenshain said.
Over the past few years, Bluebird has struggled with clinical setbacks, a failed commercialization in Europe, the departure of its longtime leader Nick Leschly, and significant layoffs. Bluebird has about 300 employees today, 42 percent fewer than at the end of January.
Skysona is designed to restore a crucial gene that is broken in children with a condition called cerebral adrenoleukodystrophy. The disease, which primarily affects boys ages 4 to 10, damages brain cells and causes progressive loss of cognitive and physical abilities — including hearing, vision, and movement. For many, it is fatal within five years.
“This is a very devastating disease that quickly progresses from initial symptoms,” said Dr. David A. Williams, chief of hematology/oncology at Boston Children’s Hospital, who led one clinical trial of Skysona. “You can have a six-year-old son who’s perfectly normal, and then five years later, they’re vegetative.”
Bluebird’s therapy could help change that. In clinical trials, which initially followed patients for two years, 92 percent of children who got Skysona survived without developing any major functional disabilities, compared to 57 percent of untreated children.
Although stem cell transplants are sometimes used to treat the disease, only about 1 in 10 patients has a matched sibling donor. Skysona’s effectiveness was similar to that of matched stem cell transplants, but patients receiving the gene therapy fared better than those who got mismatched transplants, where only 43 percent survived two years without serious disability.
“For patients who don’t have a matched sibling donor, this therapy really does move the needle,” said Dr. Christine Duncan, a medical director of the gene therapy program at Boston Children’s, and a lead investigator of one of the clinical trials.
The approval was expected but not guaranteed. At an FDA meeting in June, regulators raised questions about Skysona’s safety and long-term effectiveness. Nonetheless, the FDA’s advisory committee — a panel of independent doctors and scientists — voted unanimously that the treatment’s benefits outweigh any risks, including blood cancers that a few patients developed after getting the therapy.
In August, the FDA approved Bluebird’s first gene therapy, Zynteglo, for treating a genetic blood disease called beta thalassemia. That one-time therapy costs $2.8 million and the firm expects that up to 850 patients may qualify for it in the United States. Bluebird also plans to submit its third gene therapy — for treating sickle cell disease — to the FDA in the first quarter of 2023.
The positive news has helped the company’s stock double since its low in June, but it is still down more than 94 percent since its high in 2018. The company expects its cash and near-term income to carry the firm through the first half of 2024.
Zynteglo and Skysona were previously approved in Europe, but Bluebird began winding down its commercial operations there last fall after struggling to get European governments to cover the cost of the pricey treatments. Bluebird hopes to have better luck in the United States, where two other expensive gene therapies, Luxturna for inherited blindness and Zolgensma for spinal muscular atrophy, are already approved and covered.
Despite the high price, Skysona will have a modest impact on Bluebird’s bottom line since the disease is so rare. The company previously said it anticipates treating just 10 patients a year. Boston Children’s, which led clinical studies of Skysona, is one of the few medical centers qualified to offer the treatment.
Skysona is designed to restore production of a crucial protein that helps cells get rid of a particular class of fat molecules. Without that protein, the fat molecules build up to toxic levels that damage the brain and adrenal glands. Treatment starts with a hospital visit where physicians collect a patient’s blood stem cells. The cells are then shipped to Bluebird’s manufacturer, where scientists treat them with a virus that delivers a gene for the fat-busting protein into the cells.
After the altered cells are shipped back to the hospital, the patient receives chemotherapy to make room for the cells in their bone marrow. Once they engraft, the cells will divide, and some of their progeny will migrate into the brain where they mature into a special class of immune cells called microglia that break down the toxic fat molecules and prevent further damage to the brain.
But the therapy is not a panacea. Williams said many children will still need to take hydrocortisone to compensate for their damaged adrenal glands. The treatment also takes some time to work. “The disease can progress after the treatment for another 12 to 18 months, and then it’s arrested,” he added.
Duncan said getting patients treated early is essential. When boys are given stem cell transplants before developing neurological symptoms, the disease doesn’t noticeably progress, she said. “We expect that to be true with gene therapy as well.”
The therapy is also not without risks. Three of the 67 children treated during clinical trials developed blood cancers researchers believe are related to the gene therapy. Duncan said the risk is a “real concern,” but the cancers are treatable, and that unmatched stem cell transplants carry major risks as well. “I still believe that this is a good option for some patients.”
The FDA approval comes with a warning about the risk of blood cancer and the requirement for biannual and annual tests to detect early signs of cancer. The FDA also told Bluebird that it must continue following patients for 15 years after receiving the therapy to collect data on its long-term safety and effectiveness.
Ryan Cross can be reached at firstname.lastname@example.org. Follow him on Twitter @RLCscienceboss.