- Bluebird bio on Wednesday said its experimental gene therapy for sickle cell disease is "very unlikely" related to a recently diagnosed case of leukemia in the one of the company's clinical trials, citing findings from an investigation into the genetic make-up of the study volunteer's tumor.
- Bluebird had stopped two studies of the treatment in response to the diagnosis, which was disclosed in mid-February, and suspended sales of a related gene therapy product called Zynteglo that's approved for use in Europe.
- The leukemia case, as well as the disclosure by Bluebird of cancer-like bone marrow disease in another study volunteer, renewed concerns about gene therapy safety that may be hard to quickly dispel. Bluebird's investigation into the other report of myelodysplastic syndrome remains ongoing, although the company said Wednesday it's not clear whether the participant formally meets the criteria for a diagnosis.
Bluebird's investigation focused on the inactive virus the company uses to genetically engineer a patient's stem cells into a therapeutic treatment.
When the company first disclosed the case of acute myeloid leukemia last month, it noted there were genetic traces of the treatment in the volunteer's cancerous cells. The question facing Bluebird was whether its so-called viral vector had "driven" cancer-causing mutations in those cells or was merely a "passenger" in the spontaneous development of leukemia, rates of which are higher among sickle cell patients than in the general population.
An update from company executives at a virtual investor conference suggested the latter, noting the patient's tumor had several significant "chromosomal abnormalities" and genetic mutations that are often observed in acute myeloid leukemia, or AML
Wednesday's update goes even further, with Bluebird revealing that tests showed its vector "integrated," or fused into, the genome of the leukemic cells at a sequence for a gene called VAMP4. There's no known association between VAMP4 and AML, and the gene's role doesn't involve cellular growth or maintaining DNA health, according to Bluebird's Chief Scientific Officer Philip Gregory.
"The totality of data and publications publicly available support no role for VAMP4 in oncogenesis," he said in Wednesday's statement. "Moreover the VAMP4 integration site is not in the vicinity of any gene of particular interest such as a parent oncogene or tumor suppressor."
Moreover, vector integration into VAMP4 has been found in a "majority of patients" in Bluebird's trial, the company said, with no other cases of leukemia.
While Bluebird's findings don't completely preclude the possibility its gene therapy may played some role, the company appears confident the likelihood is slim. Additionally, the data so far indicates the cancer was not the result of a chemotherapy regimen given to patients to prepare them for gene therapy treatment.
"The conditioning probably did not play a role [...] in this case," said David Davidson, Bluebird's chief medical officer, on a conference call Wednesday.
Bluebird aims to soon restart its halted clinical studies, noting Wednesday that it has shared information from its investigation with the Food and Drug Administration. In Europe, regulators are meeting this week to determine whether any additional monitoring steps should be taken for Bluebird's Zynteglo gene therapy, which was approved to treat beta thalassemia and uses the same vector as the company's sickle cell product.
News of Bluebird's findings boosted the value of company shares, which rose by as much as 14% Wednesday morning. Shares in other gene therapy developers that use a similar virus for their treatments, like Avrobio, Orchard Therapeutics and Rocket Pharmaceuticals, also gained on the news.