- Modifications made by Bluebird bio to its experimental gene therapy LentiGlobin appear to be delivering the hoped-for effect in patients with two genetic blood disorders, according to updated clinical results presented by the biotech Friday.
- Treatment with new versions of LentiGlobin spurred normal or near-normal production of the vital oxygen-transporting protein hemoglobin in a handful of patients with beta-thalassemia, while boosting anti-sickling hemoglobin in four patients with severe sickle cell disease.
- The results mark progress for LentiGlobin after an earlier version had run into hurdles that prompted Bluebird to change how it manufactured the therapy. Yet data from more patients, as well as longer follow-up, will be needed to further prove the durability of LentiGlobin's benefit, particularly in sickle cell disease.
Bluebird last provided data from its ongoing studies of LentiGlobin in beta-thalassemia and sickle cell disease in December. Then, the company could only offer a limited snapshot of how well the changes made to the LentiGlobin manufacturing process were translating into clinical benefit.
The results presented Friday ahead of the European Hematology Association's annual meeting paint a more convincing picture. Investors, however, seemed unenthused by Bluebird's update, sending shares in the biotech down 6% Friday morning.
In a study known as Northstar-2, 11 patients with beta-thalassemia received infusions of the new version of LentiGlobin. Seven of the eight participants who had six or more months of follow-up monitoring were producing normal or near-normal levels of hemoglobin, freeing them for the blood transfusions beta-thalassemia patients typically require to survive.
Two study participants have remained transfusion free for about a year, suggesting LentiGlobin could be a replacement of allogeneic stem cell transplantation and, possibly, an effective cure.
In an earlier, now complete trial, which used the original version of LentiGlobin, eight of 10 patients remain transfusion free with a median of nearly three years of follow-up.
One patient in the Northstar-2 study did relapse, however, requiring a transfusion after 11 months of freedom from transfusion. Bluebird noted the patient had a particularly low peripheral vector copy number, suggesting a less optimal uptake of the infused therapy. On a call with analysts Friday morning, Bluebird CEO Nick Leschly said the company considers that patient an outlier.
And in the earlier trial, called Northstar, a patient who was reported free from chronic transfusions in December was no longer listed as such in the most recent update.
There were no graft failures or vector-mediated replication competent lentivirus reported and overall safety appears consistent with myeloablative conditioning, Bluebird said.
Bluebird plans to file LentiGlobin in Europe for transfusion-dependent beta-thalassemia later this year, and says these results show it remains on track to do so. In the U.S., more data will be collected before submitting for approval.
In sickle cell disease, Bluebird reported data on only four patients who had been monitored for more than three months following infusion. But what it has seen from these initial few has boosted its confidence in the program, which had stumbled after seeing promising results in the very first patient treated with the original LentiGlobin process and product.
"We feel we have turned a corner in our sickle cell disease program," Leschly said on the Friday conference call.
All four patients were greater than 30% anti-sickling hemoglobin, exceeding the targeted threshold for demonstrating therapeutic benefit.
Notably, all six patients infused with the new LentiGlobin reported higher vector copy numbers and percentage of transduced cells, underscoring the improvements from the older version. Bluebird has reported that higher vector copy numbers appear correlated with increased production of anti-sickling hemoglobin.
No new safety findings were reported with the updated method.
Bluebird's hope is that LentiGlobin will prove capable of converting actively symptomatic sickle cell patients into "sickle cell trait," in other words a carrier but without symptoms.