Long-term Follow-up Data From bluebird’s Gene Therapy Program in Sickle Cell Disease Support Durable, Potentially Curative Benefits Through Stable Production of Anti-Sickling Adult Hemoglobin and Resolution of Vaso-Occlusive Events
Oral presentation to include data on 47 patients through five years of follow-up (median 35.5 months, range 0.3-61 months)
Endpoints of sVOE-CR and VOE-CR achieved in 94% (32/34) and 88% (30/34) of evaluable patients respectively
100% of adolescents (10/10) experienced complete resolution of VOEs and sVOEs, providing evidence of potential benefit for this population
Impact on hemolysis markers and health-related quality of life measures further support potential therapeutic benefits
SOMERVILLE, Mass.--(BUSINESS WIRE)--Dec. 9, 2023-- bluebird bio, Inc. (NASDAQ: BLUE) (“bluebird bio” or “bluebird”) today announced new and updated efficacy, safety and health-related quality of life (HRQoL) data from the Phase 1/2 HGB-206 Group C and Phase 3 HGB-210 studies of lovotibeglogene autotemcel (lovo-cel) gene therapy for sickle cell disease through five years of follow-up (median 35.5 months, range 0.3-61 months). Data were highlighted in a press briefing at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition and will be presented in an oral presentation on Monday, December 11, 2023 at 4:30 p.m. Pacific Time.
“Years of long-term follow-up continue to suggest that lovo-cel has the potential to address the underlying cause of sickle cell disease and provide robust clinical benefits for patients,” said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “The data presented at ASH give us confidence that these results can be sustained over time and may translate to meaningful and lasting impact on quality of life for people living with sickle cell disease who need and deserve new treatment options.”
The analysis presented at ASH focused on 47 people living with sickle cell disease who received lovo-cel in the HGB-206 Group C and HGB-210 studies following enhancements to the treatment process and manufacturing protocols. Over 85% of patients required ≤2 mobilization cycles prior to infusion. As of the February 13, 2023 cutoff date, all patients had stable production of anti-sickling adult hemoglobin after infusion through last follow-up (median >40% HbAT87Q), and vaso-occlusive events (VOEs) and severe vaso-occlusive events (sVOEs) were eliminated or significantly reduced in all patients, further suggesting that lovo-cel has shown a durable impact on the underlying cause of sickle cell disease. The majority of adverse events in treated patients were attributed to underlying sickle cell disease or conditioning with busulfan.
Lovo-cel is the most deeply studied gene therapy in development for sickle cell disease, with the most patients treated and longest follow-up in the field. As of February 13, 2023, 59 patients were treated across the entire clinical development program with follow-up beyond 8 years in the earliest treated patients.
The therapy was approved on December 8, 2023 by the U.S. Food and Drug Administration and is currently marketed as LYFGENIA in the U.S.
Updated efficacy data continue to support transformational impact on VOE burden
In the studies, 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 chest syndrome requiring oxygen treatment and/or blood transfusion, acute hepatic sequestration, acute priapism lasting 2 hours and requiring care at a medical facility and acute splenic sequestration. sVOEs require 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; all VOEs of priapism are also considered sVOEs.
As of February 13, 2023, 34 of the 47 patients treated in HGB-206 Group C and HGB-210 were evaluable for the primary and secondary endpoints of complete resolution of VOEs and sVOEs with a median follow-up 36.3 months (12.1, 61).
32/34 patients (94%) experienced complete resolution of sVOEs, maintained for a median (min, max) of 35.8 months (20.2, 61).
30/34 patients (88.2%) experienced complete resolution of all VOEs, maintained for a median (min, max) of 35.8 months (20.2, 61).
Patients who experienced VOEs at any time post-treatment through long-term follow-up (n=8) experienced significant reduction in VOE frequency and severity compared to before treatment.
All 8 patients experienced a reduction in VOEs of at least 50%.
Hospital days and admissions were reduced by as much as 100% (annualized median hospital days reduced from 15.75 (3.5, 136) pre-treatment to 2.20 (0.0, 25.4); (annualized median reduction in hospital days was 85.5% (31.7%, 100%).
Results of a sub-analysis of data from adolescent patients, presented for the first time, showed complete resolution of VOEs and sVOEs in 10/10 (100%) of patients during the 6-18 month enrollment period.
“These new data provide further evidence that lovo-cel can provide significant improvements in quality of life for people living with sickle cell disease and that the effects are durable for at least five years,” said Julie Kanter, M.D., a lovo-cel investigator and director of the University of Alabama Birmingham Adult Sickle Cell Clinic and associate professor in the Division of Hematology and Oncology. “We see meaningful changes in hemoglobin, excellent production of anti-sickling hemoglobin, and improvement in all markers of hemolysis which further reinforces the clinical effects of lovo-cel. This one-time, transformative therapy has the potential to target the underlying cause of the disease and reduce both pain and fatigue—outcomes that matter to people living with sickle cell disease and their families. These findings support the positive impact of lovo-cel on the biology of sickle cell disease and on patients’ clinical outcomes and quality of life.”
Clinical outcomes were further supported by improvements in total hemoglobin and markers of hemolysis
Red blood cells normally break down in the body through a naturally occurring process called hemolysis. In sickle cell disease, hemolysis happens too quickly due to the fragility of sickled red blood cells, resulting in hemolytic anemia. With the exception of patients with alpha-thalassemia trait, all patients had improvement in total hemoglobin and markers of hemolysis; improvements were sustained through last follow-up. As of the February 13, 2023 cut-off date:
Following engraftment, non-transfused total Hb and %Hb fractions stabilized by approximately 6 months after lovo-cel infusion.
Median percent of gene-therapy derived anti-sickling adult hemoglobin (HbAT87Q) was maintained generally at >40% of non-transfused total Hb throughout follow-up.
From six months post-infusion through the last visit, several indicators of the health of red blood cells suggest that treatment with lovo-cel improved biological markers for sickle cell disease to normal or near-normal levels. Lactate dehydrogenase and indirect bilirubin levels normalized and reticulocyte counts approached normal levels.
The majority of patients experienced sustained improvements in key domains of health-related quality of life measures
The burden of sickle cell disease impacts every aspect of patients' lives. Health-related quality of life (HRQoL) findings in patients treated in HGB-206 Group C were generated using the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), a validated instrument in sickle cell disease.
Improvements in key domains including pain interference, pain intensity, and fatigue were demonstrated, showing statistically significant improvements as early as month six which were sustained up to 36 months for pain intensity and 48 months for pain interference and fatigue. These findings provide a broader understanding of the potential impact to daily life over time following treatment with lovo-cel.
