- Bluebird bio can resume enrolling and treating children and adolescents with sickle cell disease after the Food and Drug Administration lifted a clinical hold on the biotechnology company’s gene therapy for the blood disorder.
- The agency had imposed the partial study suspension in December 2021 after one trial participant developed a potentially concerning case of persistent anemia. The hold’s removal, which Bluebird announced Monday, follows recent data linking the case, along with another observed in an adult participant, to an underlying genetic condition known as alpha thalassemia trait.
- Bluebird plans to restart enrollment in the first quarter of 2023, which is also when it plans to submit an approval application to the FDA for its therapy, called lovo-cel. Shares in the biotech fell by more than 11% in morning trading Monday.
Monday’s news is another step forward for Bluebird, which spent much of 2022 in financial distress but in August and September won FDA approvals of two rare disease gene therapies.
Neither of those two treatments — Zynteglo for a severe form of beta thalassemia and Skysona for a childhood brain disease — are expected to be big sellers, however, as the number of patients they’re respectively cleared to treat is small.
Lovo-cel, if approved, would be for a much larger market and, as such, figures prominently in the company’s future plans. Clinical trial results have shown treatment with it can eliminate the severe pain crises that sickle cell patients frequently experience, while reducing the proportion of red blood cells that are sickled in shape.
But development, which has stretched over nearly a decade, has recently been slowed by safety concerns. In February 2021, Bluebird stopped studies of its therapy after one participant developed acute myeloid leukemia and another was suspected to have a cancer-like disease of the bone marrow called myelodysplastic syndrome. An investigation determined the leukemia to be unrelated to treatment, and found the suspected myelodysplastic syndrome was actually transfusion-related anemia. The FDA let Bluebird resume testing in June 2021.
Testing was partially stopped again in December last year due to a pediatric case of persistent anemia, which can be a potential warning sign of blood cancer developing. This time, the FDA allowed treatment of adult patients to continue, while halting enrollment and dosing of children and teenagers.
Data presented earlier this month at the American Society of Hematology’s annual meeting suggested the anemia was related to the patient’s underlying genetics, rather than to treatment. Both the pediatric patient and an adult who later developed anemia had alpha thalassemia trait, which is associated with the blood disease. Bluebird believes its treatment may have exacerbated the condition and plans to screen patients with the genetic trait out of its studies in the future.
Alpha thalassemia trait is estimated to affect about 4% of people with sickle cell disease, according to Dane Leone, an analyst at the investment bank Raymond James.
With that data in hand, Bluebird was able to resolve the FDA’s partial hold, clearing the way for the anticipated submission of lovo-cel for approval.
“We see this news as reasonable and expected, given the data presented at ASH, and as reflection of a progressively more navigable regulatory environment for cell and gene therapies,” SVB Securities analyst Mani Foroohar wrote in a Monday note to clients.
Bluebird has several would-be competitors in sickle cell gene therapy, foremost among them Vertex Pharmaceuticals and CRISPR Therapeutics. The partnered drugmakers have developed a gene editing treatment for the condition and are currently submitting an approval application to the FDA on a rolling basis. They plan to complete their filing in the first quarter, after which the FDA would begin its review.