Gene Therapy May Eliminate Life-Long Need for Transfusions in Patients with Incurable Blood Disorder

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Pioneering Gene Therapy by UCSF Benioff Children’s Hospital Oakland Researchers Demonstrates Gene Therapy Can Eliminate Life-Long Need for Transfusions in Patients with Incurable Blood Disorder


Data from Clinical Studies of Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia Show Majority of Patients Are Transfusion-free

Oakland, CA  – Interim results of clinical trials by investigators at UCSF Benioff Children’s Hospital Oakland and Ann and Robert H. Lurie Children’s Hospital of Chicago reveal that a majority of the 22 patients in two Phase 1/2 studies followed for two years or longer remained free from transfusions. The results of the trials “Gene Therapy in Patients with Transfusion-Dependentβ-Thalassemia,” are published today in the New England Journal of Medicine (NEJM).

The results are from two separate, two-year clinical studies using LentiGlobin® gene therapy to stop or reduce chronic blood transfusions in patients with transfusion-dependent β-thalassemia (TDT).
Beta-thalassemia is a blood disorder caused by a mutation in the HBB gene that reduces production of the protein hemoglobin, which affects the blood’s ability to transport oxygen and is associated with life-threatening complications such as severe anemia and organ damage. Patients with more severe forms of beta-thalassemia require frequent blood transfusions to replace their unhealthy blood with healthy blood. However, transfusion-related complications such as iron overload can be deadly.

Both studies, Northstar (HGB-204), which recently was completed, and HGB-205, which is ongoing, are evaluating the safety and efficacy of one-time treatment with LentiGlobin® gene therapy and the interim results showed that 15 of the 22 patients in the two Phase 1/2 studies followed for two years or longer were able to stop blood transfusions.

Interim results also showed that all but one patient with a non-β0/β0 genotype (12 of 13 patients) stopped receiving regular red blood cell (RBC) transfusions, with a median time since last transfusion of 27 months. In the nine patients with a β0/β0 genotype or similar severity, median transfusion volume decreased by 73 percent, and RBC transfusions were stopped in three patients. Treatment with LentiGlobin® is given as an autologous stem cell transplant.

Dr. Mark C. Walters of UCSF Benioff Children’s Hospital Oakland has been the lead researcher for the Northstar Study (HGB-204): A Phase I/II Study of Gene Therapy for Beta-Thalassemia Major via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex-Vivo with a Lentiviral Beta AT87Q-Globin Vector (LentiGlobin BB305 Drug Product).  LentiGlobin BB305, produced by BlueBird Bio, uses a non-communicable virus to deliver a fully functioning HBB gene to a patient’s own blood-producing stem cells.
This Phase I/II study has examined if using LentiGlobin BB305 to introduce a fully functioning hemoglobin gene into a patient’s stem cells was a safe and effective treatment. Dr. Walters collected stem cells from transfusion-dependent beta-thalassemia major patients, inserted the healthy gene, and then infused the cells back into the patient after first giving high-dose chemotherapy to destroy the thalassemia-producing blood cells.

Eighteen transfusion-dependent beta-thalassemia major patients received LentiGlobin BB305 therapy. The modified gene was inserted in all patients and produced the corrected hemoglobin. Of the 18  patients who were treated, after two years, 11 were transfusion-free. Ten of the 18 patients have HBB gene mutations that are associated with reduced, but not totally absent, production of functional hemoglobin.

“These important results show that gene therapy is a promising new option for reducing or eliminating blood transfusions and limiting long-term complications of transfusions in patients with this disease,” says Dr. Mark C. Walters, Director of the Blood & Marrow Transplantation (BMT) program at UCSF Benioff Children’s Hospital Oakland and lead investigator of the Northstar study.
Interim Safety Results of the Northstar and HGB 205-Studies

The safety profile of LentiGlobin in TDT continues to be consistent with myeloablative conditioning with the chemotherapy agent busulfan. In the Northstar study, five mild adverse events (AEs), all Grade 1, were characterized as possibly or probably related to LentiGlobin. Nine serious adverse events (SAEs) were reported, including two episodes of veno-occlusive liver disease; none were considered related to LentiGlobin. In HGB-205, there were three SAEs, all Grade 2 or 3.  For both studies, all adverse events were treated with standard measures. There was no evidence of a single gene clone becoming dominant or of any patient developing a replication-competent strain of the viral vector.  All patients who were engrafted survived.

About UCSF Benioff Children’s Hospitals:
UCSF Benioff Children’s Hospitals are among the nation’s finest pediatric medical centers, according to U.S. News & World Report’s annual rankings. Their expertise covers virtually all pediatric conditions, including cancer, heart disease, neurological disorders, pulmonology, diabetes and endocrinology, as well as the care of critically ill newborns. The nonprofit UCSF Benioff Children’s Hospitals are committed to providing outstanding care to children in the Bay Area, California and beyond. They are known nationally and internationally for basic and clinical research, and are at the forefront of translating research into interventions for treating and preventing diseases. The Oakland campus has a highly regarded pediatric residency program and is one of only five ACS Pediatric level I trauma centers in California. The San Francisco campus is part of UC San Francisco, whose schools of Medicine, Pharmacy, Dentistry and Nursing lead the nation in research grants from the National Institutes of Health.



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