Bluebird Bio released incredible clinical data this weekend at ASH for people suffering with sickle cell disease.

bluebird bio, Inc. (Nasdaq: BLUE) announced new data from its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin™ gene therapy for sickle cell disease (SCD), including additional patients treated in the study and updated data for those previously reported. These data, as well as results from exploratory assays designed to assess the relationship between drug product characteristics and red blood cell physiology, were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

Highlights:

99% reduction in annualized rate of vaso-occlusive crises (VOC) and acute chest syndrome (ACS) in Group C patients with history of VOCs and ACS who had at least six months follow-up, no reports of ACS or serious VOCs at up to 21 months post-treatment

Group C patients at six months post-treatment produced consistent median levels of gene therapy-derived anti-sickling hemoglobin (HbAT87Q) ranging from 44 – 59% (Month 6 – 21), reducing the median level of abnormal sickle hemoglobin (HbS)

Continued improvement in key markers of hemolysis in Group C patients demonstrates the potential of LentiGlobin for SCD to modify the underlying pathophysiology of sickle cell disease

“At ASH, the growing body of data from our clinical studies of LentiGlobin for SCD reflects results from 26 treated patients with up to four years of follow-up,” said David Davidson, M.D., chief medical officer, bluebird bio. “We continue to observe patients treated in Group C producing high levels of gene-therapy derived anti-sickling hemoglobin, HbAT87Q, accounting for at least 40% of total hemoglobin in those with six or more months of follow-up, and exploratory assays show that HbAT87Q is present in most red blood cells of treated patients. The robust production of HbAT87Q was associated with substantial reductions of sickle hemoglobin, HbS, as well as improvement in key markers of hemolysis. Most importantly, patients in Group C have not experienced any episodes of acute chest syndrome or serious vaso-occlusive crises following LentiGlobin for SCD treatment.”

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive crises (VOCs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome (ACS), stroke and infections, which can contribute to early mortality in these patients.

LentiGlobin for SCD was designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their RBCs can produce anti-sickling hemoglobin that decreases the proportion of sickled hemoglobin, with the goal of reducing sickled RBCs, hemolysis and other complications.

“People living with sickle cell disease face a lifetime of unpredictable pain, hospitalizations and increased risk of stroke and premature death,” said Julie Kanter, M.D., University of Alabama at Birmingham. “It is so exciting to see the Group C results from the HGB-206 study. The data continue to demonstrate sustained expression of gene therapy-derived hemoglobin in patients treated with LentiGlobin for SCD, which resulted in significantly improved hemoglobin (>2g/dl/patient), near-normalization of markers of hemolysis and no reports of acute chest syndrome, stroke or serious vaso-occlusive crises in these patients.”

As of the data cutoff date, 17 patients were treated with LentiGlobin for SCD in Group C, with the longest follow-up at 21 months; none required regular RBC transfusions post-treatment.

In patients with six or more months of follow-up (n=12), median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were at least 40% of total hemoglobin. Total hemoglobin and HbAT87Q levels ranged from 9.3 – 15.2 g/dL and 2.7 – 9.0 g/dL, respectively, at last visit.

Treatment with LentiGlobin for SCD reduced key markers of hemolysis, including reticulocyte counts, lactate dehydrogenase (LDH) levels and total bilirubin concentration, which suggests that treatment is improving biological markers of the disease.

Among the nine patients with at least six months of follow-up who had four or more VOC or ACS events in the two years prior to treatment, there was a 99% reduction in annualized rate of VOC and ACS. There were no reports of ACS or serious VOC at up to 21 months post-treatment in these patients. As previously reported, there was one non-serious Grade 2 VOC was observed in a patient approximately 3.5 months post-LentiGlobin for SCD treatment.

A refined manufacturing process that increases vector copy number (VCN) and improves engraftment potential of gene-modified stem cells was used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Group A and Group B.

As of the data cutoff date, seven out of nine total patients in Groups A and B (five out of seven in Group A and two out of two in Group B) did not require regular RBC transfusions post-treatment.

All seven patients in Group A had reached at least three years of post-treatment follow-up. Levels of HbAT87Q and total hemoglobin remained durable in all seven patients. At last evaluable visit, median HbAT87Q levels were 0.9 g/dL and total hemoglobin was 9.0 g/dL.

Of the two patients in Group B, levels of HbAT87Q and total hemoglobin remained durable at two years of post-treatment follow-up. At last visit, HbAT87Q levels were 3.6 g/dL and 7.1 g/dL, and total hemoglobin was 11.3 g/dL and 13.0 g/dL.

Overall, patients in Groups A and B experienced a reduction, but not complete elimination of VOC and ACS events at two years post-treatment, suggesting that the levels of gene therapy-derived hemoglobin may have been sufficient to reduce but not eliminate continued sickle-related disease manifestations.

HGB-206 Exploratory Assays

bluebird bio presented results from exploratory assays in samples from a subset of patients treated with LentiGlobin for SCD from Groups A, B and C, to assess the relationship between drug product characteristics and RBC physiology.

To demonstrate the pancellular expression of the gene therapy derived anti-sickling Hb, HbAT87Q, bluebird bio developed an assay that enables detection of HbAT87Q and HbS protein in individual RBCs. In 12 patients who had at least six months of follow-up, the proportion of RBCs positive for HbAT87Q at the last study visit was more than 70% in all cases; with more than 90% of RBCs positive for HbAT87Q in four patients.

On average, HbAT87Q present in RBCs of patients treated with LentiGlobin for SCD was within the range of non-sickling adult Hb, HbA, present in the RBCs from people with sickle cell trait. The RBCs also resembled sickle cell trait RBCs with regard to propensity to sickle under low oxygen conditions. Sickling of RBCs from patients treated with LentiGlobin for SCD was significantly less than that seen in untreated patients with SCD.

There have been no serious adverse events related to LentiGlobin for SCD. One mild, non-serious event of hot flush was reported that the investigator considered to be related to LentiGlobin for SCD; it occurred and resolved on the day of drug product infusion and did not require treatment.

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