Bluebird Bio reported encouraging data on its revamped gene therapy for sickle cell disease (SCD) and beta thalassemia this morning, but shares slipped 6% premarket on some unresolved issues.

Two years ago, Bluebird was hit hard when a trial of its LentiGlobin candidate failed to hit the mark in a clinical trial, mainly because patients had variable responses to the treatment, which forced the company to change the manufacturing process for the drug.

The aim was to increase the number of vector copy numbers (VCN) produced and increase the number of lentiviral vector positive (LVV+) cells—i.e., those that have had their gene sequence corrected—in the hope of making responses more consistent. That new process has now been put through its paces, with what the company said are encouraging results.

The first of six patients recruited into the NorthStar-2 trial of LentiGlobin in patients with beta-thalassemia—which causes severe depletion in red blood cells—was able to completely halt regular blood transfusions within a month of treatment and saw hemoglobin levels return to normal within six months.

On the downside, the second patient in the trial showed a lower-than-expected result for a measure of hemoglobin production and VCN, raising the fear that the patient variability issue has not been wholly resolved. A third evaluable patient came in between the other two on the hemoglobin biomarker. Patients two and three have only been followed for three and two months, respectively, and as yet there is no data on total hemoglobin and transfusion rates.

“Although early, these data add to the growing body of clinical evidence that indicate that LentiGlobin may offer a transformative benefit for patients with transfusion-dependent thalassemia,” said primary investigator Alexis Thompson, M.D., of Ann & Robert H. Lurie Children’s Hospital of Chicago.

“Patients with TDT are dependent on a burdensome cycle of transfusion and chelation, and for these patients, gene therapy with LentiGlobin may offer a long-term solution with a one-time therapy that alleviates many of the complications of the current treatment paradigm,” Thompson added.

NorthStar-2 will eventually recruit 15 patients and if positive will set up possible filings for LentiGlobin in the U.S., while in Europe the drug has been accepted into the EMA’s PRME program, which allows accelerated approval, based on two earlier trials.

Bluebird also reported new data from its earlier HGB-205 trial in patients with beta-thalassemia and SCD, which used the unimproved version of LentiGlobin. It showed that the two most recently treated SCD patients are showing rising levels of the hemoglobin biomarker, and what the firm’s chief medical officer David Davidson, M.D. described as “evidence of early stabilization at a higher level compared to the initial cohort of patients,” although they are not yet improved enough to be considered cured.

The follow-up dataset also includes a beta-thalassemia patient who has gone from requiring regular transfusions to zero transfusions in the last three and a half years after a single treatment with LentiGlobin, said Davidson.


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