Benzinga | Dec 7, 2020 04:33PM EST

bluebird bio Highlights Presentation Of Data From Phase 1/2 HGB-206 Study Of LentiGlobin Gene Therapy At American Society Of Hematology Annual Meeting

No severe vaso-occlusive events (VOEs) reported through 24 months of follow-up in Group C patients who had a history of at least four severe VOEs and at least six months of follow-up (n=19)

At up to 30 months follow-up and 32 patients treated, Group C patients continue to produce consistent levels of gene therapy-derived anti-sickling hemoglobin (HbAT87Q), reducing levels of abnormal sickle hemoglobin (HbS) that cause symptoms of SCD

Positive patient-reported quality of life outcomes assessed with validated PROMIS-57 demonstrate clinically meaningful reductions in pain intensity at Month 12 post-LentiGlobin for SCD treatment

bluebird bio, Inc. (NASDAQ:BLUE) announced that new data from Group C of its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin(tm) gene therapy (bb1111) for adult and adolescent patients with sickle cell disease (SCD) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up. These data are being presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020.

"Now with more than two years of data, we continue to observe promising results in our studies of LentiGlobin for SCD that further illustrate its potential to eliminate the symptoms and devastating complications of sickle cell disease. Consistently achieving the complete resolution of severe vaso-occlusive events (VOEs) and VOEs between Month 6 and Month 24 follow-up is unprecedented other than with allogeneic stem cell transplantation. Importantly, our data show the potential for LentiGlobin for SCD to produce fundamentally disease-modifying effects with sustained pancellular distribution of gene therapy-derived anti-sickling HbAT87Q and improvement of key markers of hemolysis that approach normal levels," said David Davidson, M.D., chief medical officer, bluebird bio. "In addition to these clinical outcomes, for the first time with a gene therapy we now have patient-reported outcomes through the validated PROMIS-57 tool, showing reduction in pain intensity at 12 months after treatment with LentiGlobin for SCD. These results provide insight into the potential real-life impact LentiGlobin for SCD may offer patients."

SCD is a serious, progressive and debilitating genetic disease. In the U.S., the median age of death for someone with sickle cell disease is 43 -- 46 years. SCD is caused by a mutation in the ?-globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs.

In the HGB-206 study of LentiGlobin for SCD, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.

LentiGlobin for SCD was designed to add functional copies of a modified form of the ?-globin gene (?A-T87Q-globin gene) into a patient's own hematopoietic (blood) stem cells (HSCs). Once patients have the ?A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

"As a hematologist, I regularly see the debilitating effects of pain events caused by sickle cell disease. Pain has an overwhelmingly negative impact on many facets of my patients' lives and can lead to prolonged hospitalizations," said presenting study author Alexis A. Thompson, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine and head of hematology at Ann and Robert H. Lurie Children's Hospital of Chicago. "The results observed with LentiGlobin gene therapy for SCD include the complete elimination of severe vaso-occlusive pain episodes, which is certainly clinically meaningful, but also for the first time, we have documented patients reporting that they are experiencing improved quality of life. This degree of early clinical benefit is extraordinarily rewarding to observe as a provider."

As of the data cut-off date of August 20, 2020, a total of 44 patients have been treated with LentiGlobin for SCD in the HGB-205 (n=3) and HGB-206 (n=41) clinical studies. The HGB-206 total includes: Groups A (n=7), B (n=2) and C (n=32).

HGB-206: Group C Updated Efficacy Results

The 32 patients treated with LentiGlobin for SCD gene therapy in Group C of HGB-206 had up to 30.9 months of follow-up (median of 13.0; min-max: 1.1 -- 30.9 months).

In patients with six or more months of follow-up whose hemoglobin fractions were available (n=22), median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Q contributing at least 40% of total hemoglobin at Month 6. At last visit reported, total hemoglobin ranged from 9.6 -- 15.1 g/dL and HbAT87Q levels ranged from 2.7 -- 8.9 g/dL. At Month 6, the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin; median HbS was 50% and remained less than 60% at all follow-up timepoints. All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.

Nineteen patients treated in Group C had a history of severe VOEs, defined as at least four severe VOEs in the 24 months prior to informed consent (annualized rate of severe VOE min-max: 2.0 -- 10.5 events) and at least six months follow-up after treatment with LentiGlobin for SCD. There have been no reports of severe VOEs in these Group C patients following treatment with LentiGlobin for SCD. In addition, all 19 patients had a complete resolution of VOEs after Month 6.