- Bluebird bio will pause enrollment and treatment of young patients with sickle cell disease in three clinical trials testing the biotech company's gene therapy for the blood condition, announcing Monday the Food and Drug Administration has placed a partial clinical hold on the studies.
- The hold, a regulatory tool used to temporarily stop testing, only applies to study volunteers under the age of 18; enrollment and dosing of patients older than 18 will continue, Bluebird said. The FDA placed the hold in response to a Bluebird investigation of one younger study participant who developed persistent anemia a year and a half following treatment with the gene therapy.
- Bluebird said it expects to receive written feedback from the FDA in early 2022 and will work quickly to resolve the regulator's concerns. The company said it's "evaluating" whether the hold will delay its plans to submit the gene therapy for approval in the first quarter of 2023.
While the eventual impact of the FDA's hold is unclear, it's another hurdle for a company that's been stung by a series of setbacks and delays. Shares in Bluebird, which recently spun out its cancer business into a separate company, fell by 20% Monday on the news.
Bluebird only cleared a previous trial hold placed by the FDA on several of its gene therapy studies in June, after an investigation had determined its treatment was unlikely to have caused a case of acute myeloid leukemia in one trial volunteer.
The new hold also relates to safety concerns; this time from the chronic anemia one adolescent participant developed. Anemia, or a lack of sufficient numbers of red blood cells to transport oxygen throughout the body, is common after stem cell transplants, which can be used to treat sickle cell disease.
But generally such anemia occurs early, as a result of treatment used to prepare patients for the transplant, wrote Mani Foroohar, an analyst at SVB Leerink who covers Bluebird, in a note to clients. Chronic anemia 18 months after treatment, he said, could potentially be the result of blood cancer or disruption to the process by which stem cells transform into red blood cells.
In its statement, Bluebird said the patient is "clinically well" and has no evidence of cancer or the predominance of cell "clones" that could suggest its development.
"Consistent with the FDA’s direction, we have paused enrollment and treatment of patients younger than 18 in our SCD clinical program, and we will continue to work collaboratively with the FDA to understand and address their concerns," said Richard Colvin, Bluebird's chief medical officer, in the company's statement.
So far, Bluebird has treated nearly 50 sickle cell patients with its gene therapy, which testing has shown eliminates the severe pain crises that people with the disease commonly experience. The company claims it already has enough trial evidence to meet the FDA's requirements for a drug approval application, but still needs to prove its commercial manufacturing process is similar to what it used during clinical trials.
Called lovo-cel, Bluebird's treatment uses a type of virus to shuttle copies of a hemoglobin gene into patient stem cells that it has extracted. Once reinfused back into the body, those corrected stem cells are meant to grow into functional red blood cells, thereby treating the cause of sickle cell.
But the delays to Bluebird's therapy have opened the door to competitors. A gene editing treatment developed by CRISPR Therapeutics and Vertex Pharmaceuticals is advancing quickly and could offer similarly powerful benefits to patients.
Bluebird recently applied to the FDA for approval of a similar gene therapy to lovo-cel, but for the blood disease beta thalassemia. A decision from the regulator is expected by next May.