CRISPR Tx Shares Fall as bluebird's Gene Therapy Soars
Last week, the U.S. Food and Drug Administration’s Cell, Tissue and Gene Therapies Advisory Committee unanimously supported bluebird’s beti-cel, a one-time gene therapy for patients with transfusion-dependent beta-thalassemia, a rare, inherited blood disorder caused by a genetic defect in hemoglobin.
Beti-cel, also known as betibeglogene autotemcel, is marketed in Europe as Zynteglo. Late-stage clinical data showed that 89% of patients who could be evaluated achieved transfusion independence following treatment with beti-cel, and safety data has been positive. The FDA is expected to give its final verdict on beti-cel by Aug. 19.
One day after the advisory committee endorsed beti-cel for beta-thalassemia, CRISPR Therapeutics and its partner Vertex Pharmaceuticals released positive data for their gene therapy candidate, exa-cel. Exa-cel is a CRISPR-Cas9-based gene editing therapy for both transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD).
Data shared by the companies showed that 42 of 44 patients with TDT who received exa-cel have remained transfusion free for up to 37.2 months. The two patients who were not transfusion free had 75% and 89% reductions in transfusion volume, the companies said.
In SCD, the data was also positive. All 31 patients with sickle cell disease that is characterized by recurrent vaso-occlusive crises (VOCs) were free of the events following treatment with exa-cel. Data showed the patients had a duration of up to 32.3 months, CRISPR and Vertex reported, which expanded their partnership in this space last year.
Carmen Bozie, head of global medicines development and medical affairs at Vertex, touted the data. Bozie noted that of the 75 patients treated with exa-cel, 33 have one year or more of follow-up after infusion with the gene therapy. The data demonstrate the potential of exa-cel as a one-time functional cure for patients with transfusion-dependent beta-thalassemia or severe sickle cell disease, she said in a statement.
While bluebird’s beti-cel was largely free of serious adverse events, Vertex and CRISPR reported that two of the 44 TDT patients experienced an SAE. One of the patients experienced three serious events that were connected to exa-cel, as well as busulfan, which was administered along with the gene therapy. That patient experienced hemophagocytic lymphohistiocytosis (HLH), a life-threatening condition related to excessive immune response, as well as acute respiratory distress syndrome and headache. The other patient experienced idiopathic pneumonia syndrome that was considered related to both exa-cel and busulfan, the companies said.
Among the 31 patients with SCD, there were no SAEs considered related to exa-cel.
CRISPR and Vertex are not alone in chasing bluebird bio to market with a gene therapy for beta-thalassemia. Editas Medicine is also developing its own gene therapy for the debilitating disease.
Earlier this year, Editas won Rare Pediatric Disease designation for its experimental beta-thalassemia gene therapy, EDIT-301. The therapeutic is designed to edit the HBG1/2 promoter to disrupt the binding site of BCL11a and ameliorate disease symptoms.
In May, EDIT-301 won Orphan Drug designation for the treatment of beta-thalassemia and SCD. Editas expects to initiate a Phase I/II study of EDIT-301 in patients with transfusion-dependent beta-thalassemia later this year.