For the second time in two days, advisers to the Food and Drug Administration gave their unanimous support to an experimental gene therapy for a rare inherited disease, agreeing its benefits outweigh its risks.
The expert panel voted 13-0 in support of the treatment, developed by Bluebird bio for the blood condition beta thalassemia, which in its severe form requires regular blood transfusions and can shorten the lifespan of those affected.
“The risk-benefit balance I think is very, very clear here,” said John Coffin, an adviser and molecular biologist at Tufts University.
The FDA is currently reviewing the treatment, called beti-cel, and is expected to make a decision by August. The agency is not required to follow its advisers’ recommendations, although it typically does.
The same panel met Thursday and backed by a similar 15-0 vote another Bluebird gene therapy, eli-cel, for a brain disorder called CALD. The committee’s support gives a major lift to Bluebird, which is running out of cash and is counting on the therapies’ approvals.
“This really clears the path for us to bring these gene therapies to patients, but it also clears the path for the gene therapy space in general,” said Andrew Obenshain, Bluebird’s CEO, in an interview after the vote.
On both Thursday and Friday, advisers were asked to weigh the effectiveness of Bluebird’s therapies against concerns that treatment could cause cancer. Three CALD patients given eli-cel developed a type of bone marrow cancer many months after treatment, while Bluebird has also reported a case of leukemia in a separate study of a sickle cell gene therapy.
All three therapies are constructed from patient stem cells, which are genetically modified and then reinfused. The tool that Bluebird uses to make those changes is similar, although there are differences in design between the CALD therapy and other two.
The panel felt there were enough distinctions between the diseases and the therapies that the cancer cases linked to eli-cel weren’t relevant for beti-cel. Still, the advisers generally agreed patients should be monitored after treatment for potential signs of cancer developing.
While the FDA appeared to have significant concerns with eli-cel’s safety and with how Bluebird measured its benefit, agency scientists were more supportive of beti-cel, documents showed.
The advisers, too, viewed beti-cel’s results as particularly persuasive. In explaining their votes, advisers cited beti-cel’s “tremendous benefit” and “remarkable” efficacy, while describing the safety risks as modest compared to other treatments, chiefly stem cell transplant.
While stem cell transplants can cure beta thalassemia, they’re typically limited to patients who have a matched sibling donor, a group that Bluebird estimates represents only about 25% of patients with severe beta thalassemia. Those who don’t must take blood transfusions every two to five weeks, as well as iron-reducing treatments to compensate for the impact of the infused blood.
Stem cell transplants also have risks, such as a condition called graft-versus-host disease where the transplanted cells attack the body.
“The only curative option we were offered was a bone marrow transplant, which came with so many risks we weren’t ready to face,” said Sarah Connolly, whose daughter died from beta thalassemia. “I believe gene therapy gives patients and their families hope — hope that we didn’t have,” she told the committee.
The main benefit measured by Bluebird was what’s known as “transfusion independence,” or beta thalassemia patients’ ability to discontinue the regular blood transfusions that keep their disease at bay. In testing, 32, or 89% of 36 treated patients achieved transfusion independence, which endured for greater than two years in most and as long as four years in the few that have been followed that long.
Another five patients who were more recently treated have now achieved transfusion independence as well, Bluebird executives said.
“Being dependent on [blood transfusions] shaped every aspect of my life,” said Radhika Swah, a woman with beta thalassemia who spoke Friday. “It’s incredibly overwhelming to consider how reliant I am on blood transfusions.”
Other biotech companies are developing treatments similarly aimed at offering additional options besides stem cell transplants. Two, partners Vertex Pharmaceuticals and CRISPR Therapeutics, are developing a CRISPR-based treatment that’s posted strongly positive results in clinical testing. They plan to seek FDA approval later this year.
Bluebird could be first of them and, while beti-cel isn’t expected to become a top-seller, commercial sales could help the company stay afloat. Earlier this year, it warned investors that it might struggle to stay solvent through next year and, in April, announced it would lay off 30% of its employees.
Commercializing gene therapies isn’t an easy proposition, either. Bluebird won approval of both beti-cel and eli-cel in Europe, only to struggle to win reimbursement. The company subsequently withdrew both treatments from the market and wound down its European operations.
Obenshain said Bluebird is well positioned in the U.S., and noted rare disease drugs can be supported with smaller, more focused teams.
“You don’t need a huge footprint,” said Obenshain. “These are launches that are suited to a company of our size.”
The FDA has set target decision dates of Aug. 19 for beti-cel and Sept. 16 for eli-cel.
Editor’s note: This story has been updated to include comments from Bluebird bio’s CEO, as well as additional detail from the meeting.
Correction: A previous version of this article contained an incorrect vote tally. The vote was 13-0, not 15-0.