- New data on Bluebird Bio Inc.'s gene therapy for sickle cell disease suggest manufacturing changes made last fall are boosting the treatment's potency, although investors looking for more conclusive evidence of improvement will have to wait until later this year.
- Results from two patients treated with Bluebird's Lentiglobin therapy under the new process show a drug product with a greater number of cells containing a functioning copy of the beta-globin gene the biotech aims to insert into patient stem cells.
- While only coming from two subjects, the data should help to build confidence in Lentiglobin ahead of this year's annual meeting of the American Society of Hematology, which will also include updates on Bluebird's beta-thalassemia and multiple myeloma programs.
Given Bluebird's focus in hematology, the annual ASH conference has been a major landmark to measure progress in the company's pipeline. This year looks to be no different, with updates planned across all of Bluebird's principal drug programs.
Wednesday's release — timed to coincide with the release of study abstracts by ASH conference organizers — only includes new information on the biotech's HGB-206 study of sickle cell disease patients, however. (Although an abstract contained details on bb2121, Bluebird's CAR-T.)
Right now, the major question is whether modifications to the study protocol and manufacturing process for Lentiglobin have increased transduction and engraftment efficacy of the genetically modified stem cells. And while the abstract showcased improvement, a change in the collection process of patient stem cells mean further proof might not come until after ASH.
More players in the game
Two patients in "Group B" of HGB-206 were treated following modification of the study protocol and manufacturing process. Higher percentages of cells were successfully transduced and vector copy numbers (VCN) in vivo rose for both subjects. In one, patient 1312, the VCN seen in peripheral blood one month after infusion was well above the levels Bluebird says usually correlate to a response.
"If we have many more cells that have at least one copy [of the desired gene], we have many more players in the game that can fight for a position in the bone marrow," explained Bluebird CEO Nick Leschly. "If you have more cells going in, the more likely that they will be able to engraft. It is a sort of odds game or numbers game."
These improvements are important because earlier results from patients treated under the old methods fell short of (high) expectations.
"The initial read on both those patients are well above any of the other patients that we have effectively treated to date, with one exception [being] the index case," said Leschly, referring to the first sickle cell patient the biotech treated with Lentiglobin, who had an extraordinary response.
That one patient had set the bar high for Bluebird in sickle cell disease, but the next seven patients didn't respond in the same way. Bluebird has been working to solve that conundrum since.
In addition to the changes from last fall, Bluebird is switching the process it uses to collect stem cells from patients. Currently, the company relies on bone marrow harvesting, which can be complicated and invasive. An easier way of extracting the cells, known as apheresis, can be dangerous for sickle cell patients as it brings many sickled blood cells into circulation — potentially causing major adverse events like strokes.
An abstract unveiled by Bluebird Wednesday, however, shows that mediating that process with a stimulant known as plerixafor can help improve safety.
Bluebird will use plerixafor-mediated apheresis for all patients in "Cohort C," eight of whom had been enrolled as of July 21. Some ex vivo data on those patients will be presented at ASH, but investors might have to wait longer to see more in vivo results from that group.
Looking more broadly, Leschly is heartened by some of the major steps forward taken by other players in the cell and gene therapy sector, expressing optimism in the health of the broader therapeutic space.
"The ecosystem has evolved greatly," said Leschly. "What I would look at 18 and 19 on is a continued evolution of that, but now into the product space, into the deployment, pricing and reimbursement, into the commercial side of this question to round of all the achievements."
While Bluebird certainly remains a ways off from those considerations, the accelerating pace of new milestones reached lessens some of the regulatory and sector risk to gene therapies. Advances by companies like Novartis AG, Kite Pharma (now part of Gilead Sciences Inc.) and Spark Therapeutics Inc. help to pave the way forward while Bluebird continues to develop its science.
Editor's note: This article has been updated to include mention of an abstract published with details of Bluebird Bio Inc.'s CAR-T therapy bb2121.