Bluebird Bio scored a much-needed win on Friday when a committee of independent scientists and doctors voted unanimously in favor of recommending Food and Drug Administration approval of the firm’s two gene therapies. The panel said that the treatments’ benefits outweighed any potential risks, including blood cancers that a few trial participants developed.
Even Bluebird was taken aback by the overwhelming support. “I was hopeful we would have positive outcomes, but this was even more than I expected,” chief executive Andrew Obenshain said. “This was an enormously gratifying moment for us.”
Trading in the struggling Cambridge biotech’s stock was halted Thursday and Friday during the two-day FDA advisory panel’s meeting. Before the meeting, the stock was down 98 percent over three years following a spate of troubles, including concerns about the safety of Bluebird’s therapies and fierce debates over their costs. In April, the company said it would lay off 30 percent of its staff to maintain enough cash to last into the first half of 2023.
But the tide could be turning for the company. Over two days, the FDA’s Cell, Tissue, and Gene Therapies Advisory Committee heard from Bluebird executives, FDA scientists, and patient advocates about the safety and effectiveness of Bluebird’s therapies: beti-cel for the rare blood disease beta-thalassemia and eli-cel for a lethal neurodegenerative disease — cerebral adrenoleukodystrophy — that afflicts young children.
While the seal of approval from the committee is welcome news for Bluebird, it is not the final word for the two therapies. The FDA must rule on the therapies, and its decision is due by mid-August for beti-cel and by mid-September for eli-cel. Even then, approval does not guarantee commercial success for the therapies, which could cost millions of dollars and meet resistance from insurers.
Both therapies are based on an engineered virus called a lentiviral vector, which is used to transfer a gene into a patient’s blood stem cells. The technique promises to give patients a permanent working copy of a gene to supplant their broken or missing copy. But depending on where that new gene lands in an individual’s DNA, it can crank up the activity of other genes linked to cancer.
Dr. Wilson W. Bryan, director of the FDA’s Office of Tissues and Advanced Therapies, opened the meeting by stating the agency’s concerns about the risk of blood cancers that arose in some patients receiving Bluebird’s therapies. Although he acknowledged a “tremendous” need for cerebral adrenoleukodystrophy therapies, “patients should not be subjected to products that are ineffective or have an unfavorable risk-benefit profile,” he said.
On Thursday, Bluebird presented data indicating that 92 percent of children with cerebral adrenoleukodystrophy were still alive two years after eli-cel treatment compared to 57 percent of those without treatment. Bluebird also compared eli-cel to standard stem cell transplants sometimes used to treat the disease. The outcomes for children on eli-cel was essentially identical to children who got stem cell transplants from genetically matched donors — such as a sibling.
But children were got eli-cel fared far better than those who got transplants from a mismatched donor; only 43 percent of them survived over two years.
Those striking results were marred by blood cancers that arose in three out of 67 patients who received eli-cel. Dr. Laura Demopoulos, Bluebird’s vice president of pharmacovigilance, said the company plans to monitor signs of cancer every six months if the therapy is approved, which should be feasible since few people are expected to receive it. “We anticipate approximately 10 patients per year will be treated given the rarity of the disease,” she said.
Dr. Christine Duncan, a physician at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center said that she was “very pleased” with the committee’s vote of confidence, especially since it was not guaranteed. “Our young patients and their families stand to benefit tremendously from eli-cel,” she said in an e-mail.
On Friday, Bluebird presented data from its beta-thalassemia study in patients who require regular blood transfusions to maintain healthy levels of oxygen-carrying blood cells. Bluebird’s gene therapy, beti-cel, provides those patients with a gene that restores their ability to make healthy blood cells. About 90 percent of patients who received the treatment were able to remain transfusion-free, some for as long as seven years.
The company said that there were no cases of cancer linked to beti-cel which uses a slightly different lentiviral vector than eli-cel.
“The therapy is effective and the benefits outweigh the risks,” said Dr. Stuart Orkin, a scientist at the Harvard Stem Cell Institute and a physician at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “I think things are being carefully done, and patients should feel gratified that something will come along for them.”
The fact that clinicians on the advisory committee said the benefits of eli-cel outweighed its risks was encouraging to other biotech companies developing lentiviral gene therapies, including Worcester-based Mustang Bio. “It is definitely a bellwether, because the whole field of gene and cell therapy is still very young,” said Knut Niss, chief technology officer of the firm.
But even if the FDA ultimately approves eli-cel, the ultimate question is how the market responds to the treatment, Niss added. “To me that is the bigger bellwether.”
Another company, Boston- and London-based Orchard Therapeutics, currently sells a lentiviral gene therapy in Europe. That therapy, Libmeldy, carries a price tag of about $3.8 million, and the company has only administered it to three patients since its approval. Orchard plans to submit Libmeldy to the FDA later this year or early next.
But if Bluebird’s beti-cel or eli-cel gets FDA approval in the coming months, those therapies will be the first lentiviral gene therapies for a rare disease in the United States. “That will be an important moment,” said Dr. Bobby Gaspar, chief executive of Orchard. “And I hope what happens with Bluebird is just the start.”
Ryan Cross can be reached at email@example.com. Follow him on Twitter @RLCscienceboss.