A two-day FDA advisory committee meeting on Thursday and Friday will have much to say about the fate of struggling bluebird bio. Two of the company's three promising gene therapies are up for consideration from the agency's independent experts.
While bluebird’s beti-cel for people with B-thalassemia who require regular red blood cell transfusions appears headed for a rubber stamp on Friday, its eli-cel treatment for cerebral adrenoleukodystrophy (CALD) could have an uphill struggle, according to briefing documents from agency staffers.
First, the good news for beti-cel. The FDA documents point (PDF) to a “clinically meaningful” benefit in patients with B-thalassemia, suggesting that it could quickly pass muster with the advisory committee. The FDA doesn't always follow its adcomm's votes, but it typically does.
“Most subjects achieved transfusion independence across all ages and genotypes,” the FDA staffers said. “Durability of transfusion independence was demonstrated through approximately 39 months of available follow-up in phase 3 study subjects.”
In 2019, regulators in Europe concluded that beti-cel was effective and granted it conditional approval. But at $1.8 million for the one-time treatment, the company and national payers could not agree on a price for the therapy, known commercially as Zynteglo. Last summer, bluebird bio exited the region.
As for eli-cel, the benefit/risk profile isn’t so clear, FDA reviewers said. The one-time treatment is for children 17 and younger who don’t have an HLA-matched hematopoietic sibling donor. The safety concern is with Myelodysplastic syndrome (MDS), a type of cancer that emerged in 3 of 67 patients who have been treated with the gene therapy.
“The significant yet uncertain risk of this life-threatening complication must be considered in the context of the product’s benefit to patients,” the FDA staffers said (PDF).
There also are concerns with assessing the efficacy of eli-cel, the FDA pointed out, when compared to the standard of care—allogenic hematopoietic stem cell transplant.
“It is unclear whether eli-cel’s efficacy is non-inferior to allo-HSCT,” the agency wrote. “FDA is not confident that 24 months is sufficient time to demonstrate efficacy of eli-cel, and paucity of data beyond 24 months limits the ability to assess disease stability and durability of effect.”
For bluebird, gaining the beti-cel approval is a higher priority as it could act as a stepping stone to a nod and commercialization for its lovo-cel treatment for sickle cell disease (SCS). Bluebird plans to file for approval of lovo-cel early next year.
While the company is targeting roughly 1,500 patients for beti-cel in the U.S., there are potentially 20,000 patients it could reach with lovo-cel.
For bluebird, the stakes in the FDA reviews are high. In April, the company cut 30% of its staff after it suffered dashed hopes in Europe and delays in the U.S.