Dive Brief:

• Executives at Bluebird bio on Thursday gave investors listening to a conference hosted by bank SVB Leerink an update on their investigation into two recent cancer cases in a study of the company’s gene therapy for sickle cell disease.

• The two diagnoses are a serious safety concern, recalling past worries over the potential for gene therapy to trigger genetic mutations that might lead to cancer. In response, Bluebird halted further study of the experimental gene therapy, and suspended sales of a similar product approved in Europe for the blood disease beta thalassemia.

• New information shared by Bluebird’s CEO and chief scientific officer, however, suggest other factors than the gene therapy may have led to one of cases, a diagnosis of acute myeloid leukemia in a patient treated five years ago. And the other case, of myelodysplastic syndrome in a more recently treated trial volunteer, may not be a conclusive diagnosis, the executives said.

Dive Insight:

Whether or not Bluebird’s gene therapy, known as LentiGlobin, led to cancer is the most important question facing the company, making the executives’ exclusive disclosure of early findings to investors of note. Companies often release information they judge to be “material” to their business via a statement or filing with regulators.

Bluebird’s investigation remains ongoing, and the information shared Thursday is preliminary. The Leerink webcast is publicly accessible and Bluebird issued a press release on Feb. 22 confirming its participation in the conference. (Bluebird did not return a request for comment from BioPharma Dive by publication, but told a STAT News journalist the company would not issue a statement or file a report with the Securities and Exchange Commission.)

“Results are early, our understanding of the two cases are evolving and our dialogue with the regulators is continuing,” said Nick Leschly, Bluebird’s CEO, at the virtual Leerink conference. “We’re going to be transparent as can be with all stakeholders.”

Bluebird disclosed the two cases on Feb. 16, sharing the diagnoses reported to the company and basic information about timing. On Thursday, Philip Gregory, Bluebird’s chief scientific officer, added that testing had determined the patient with AML had several major “chromosomal abnormalities” and genetic mutations that are commonly observed with the blood cancer.

“These are all genes associated with AML, classical mutations associated with AML as well as genomic rearrangements associated with AML and provide an independent mechanism by which this AML occurred,” Gregory told investors listening to the Leerink conference.

Bluebird has found in the patient’s leukemic cells genetic sequences for the viral vector it uses to deliver its gene therapy. The question it’s now trying to answer is whether the vector is a “passenger” alongside those AML mutations or a “driver.”

Gregory noted that, to Bluebird’s knowledge, there are no confirmed cases in any gene therapy study of a lentiviral vector like the one the company uses triggering cancer by integrating into patient cells.

More information will be available in the coming weeks, Gregory said, at which point Bluebird would make a more substantive update.

The other case, of myelodysplastic syndrome, is more complex, according to the executive, and may have not met the formal criteria for a diagnosis. No “blasts,” or abnormal white blood cells, were detected in the patient’s bone marrow.

Both patients were quite sick with sickle cell disease, which could also have played a role in their developing cancer. Rates of blood cancers among people with sickle cell are anywhere from two to 10 times higher than the general population, Gregory said.

Another case of myelodysplastic syndrome diagnosed in a study participant in 2018 was determined not to be the result of gene therapy treatment.

The threat of cancer risk has shadowed the gene therapy field for decades, since several cases of leukemia were observed in an gene therapy study in France in the early 2000s. Researchers have refined and improved both their tools and their methods, and recent clinical trials have not shown any elevated cancer risk.

But Bluebird’s February disclosure came about two months after another company, UniQure, announced a participant in one of its gene therapy studies had been diagnosed with liver cancer. Investigation of that case is still ongoing. UniQure uses a different type of vector than Bluebird.