bluebird bio Announces Publication Of Case Study On First Patient With Severe Sickle Cell Disease Treated With Gene Therapy In The New England Journal of Medicine

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, today announced the publication in the New England Journal of Medicine of a case study on Patient 1204, the first patient with severe sickle cell disease (SCD) to be treated with gene therapy. This patient, who was 13 years old at the time of treatment, was treated with LentiGlobin drug product in the HGB-205 clinical study conducted in Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. The data in the publication reflect 15 months of follow-up, and a brief summary of this patient’s outcomes with 21 months of follow-up was presented at the 58th American Society of Hematology Annual Meeting in December 2016.

“We have managed this patient at Necker for more than 10 years, and standard treatments were not able to control his SCD symptoms. He had to receive blood transfusions every month to prevent severe pain crises”

“We have managed this patient at Necker for more than 10 years, and standard treatments were not able to control his SCD symptoms. He had to receive blood transfusions every month to prevent severe pain crises,” said Professor Marina Cavazzana, M.D., Ph.D., principal investigator of this study and professor of hematology at Paris Descartes University, head of the department of Biotherapy Hospital, the clinical research center of Biotherapy at Necker Enfants Malades - Greater Paris University Hospital, AP-HP and INSERM, and of the Lymphohematopoiesis Laboratory, Imagine Institute of Genetic Diseases, Paris, France. “Since receiving the autologous stem cell transplant with LentiGlobin, he has been free from severe symptoms and has resumed normal activities, without the need for further transfusions.”

“Since our initial publication of this therapeutic approach in mouse models in 2001, we are delighted to obtain such a clear proof-of-principle of its efficacy in a patient,” said Philippe Leboulch, M.D. Dr. Leboulch is professor of medicine at the University Paris-Sud and High Counselor and International Scientific Director at France’s CEA. He was a scientific founder of bluebird bio and serves as the co-chairman of its Scientific Advisory Board. Dr. Leboulch led the development of the anti-sickling T87Q globin vector used in LentiGlobin.

“We are pleased to see this case study published in NEJM and shared with the broader research community. The successful outcome in Patient 1204 demonstrates the promise of treatment with LentiGlobin gene therapy in patients with severe SCD and serves as a guide for our efforts to optimize outcomes in future patients,” said David Davidson, M.D., chief medical officer, bluebird bio. “By analyzing this patient’s experience, we have identified key variables to optimize in our ongoing HGB-206 study of LentiGlobin gene therapy in severe SCD, and we are hopeful that these protocol changes will enable subsequent patients to achieve the transformative benefit seen in Patient 1204.”

Clinical and Biological Outcomes for the First Patient with Sickle Cell Disease Treated with Gene Therapy
Patient 1204, a male patient with ß^S/ß^S genotype, was enrolled in May 2014 at 13 years of age into the HGB-205 clinical study. The patient underwent a regular transfusion regimen for 4 years prior to this study. He had an average of 1.6 SCD-related events annually in the 9 years prior to initiating transfusions, and his complications from SCD included vaso-occlusive crises, acute-chest syndrome, bilateral hip osteonecrosis, and cerebral vasculopathy. The patient underwent two bone marrow harvests to collect hematopoietic stem cells (HSCs) for gene transfer and back-up (6.2×10⁸ and 5.4×10⁸ total nucleated cells/kg harvested). CD34+ cells were enriched from the harvested marrow and then transduced with LentiGlobin BB305 lentiviral vector. The vector copy numbers (VCN; vector copies per diploid genome) for the drug product lots manufactured were 1.0 and 1.2. The patient underwent myeloablation with intravenous busulfan (2.3 to 4.8 mg/kg per day for 4 days) with daily pharmacokinetic studies and dose adjustment. Total busulfan area under the curve (AUC) was 19,363 µmol*min. After a 2-day washout, Patient 1204 was infused with LentiGlobin drug product in October 2014 at a post-thaw total dose of 5.6×10⁶ CD34+ cells/kg. RBC transfusions were to be continued after transplantation until a sufficient proportion of HbA^T87Q (25-30% of total Hb) was detected.

Neutrophil and platelet engraftment were achieved on Day +38 and Day +91 post-transplantation, respectively. HbA^T87Q levels increased steadily and RBC transfusions were discontinued after the last transfusion on Day +88. HbA^T87Q reached 5.5 g/dL (46% of total Hb) at Month 9 and continued to increase to 5.7 g/dL at Month 15 (48%), with a reciprocal decrease in HbS levels to 5.5 g/dL (46%) at Month 9, and 5.8 g/dL (49%) at Month 15. Total Hb levels have been stable between 10.6 and 12.0 g/dL since Month 6 post-transplant. HbF levels have remained below 1.0 g/dL.

Adverse events (AEs) were consistent with busulfan conditioning, and no AEs related to LentiGlobin drug product have been observed to date.

Over the 15 months since transplantation, no SCD-related clinical events or hospitalizations have occurred, contrasting favorably with the period before the patient began regular transfusions. All medications have been discontinued, including pain medication. The patient has resumed regular school attendance and reports full participation in normal physical activities.

About SCD
Sickle cell disease (SCD) is an inherited disease caused by a mutation in the ß-globin gene that results in sickle-shaped red blood cells. The disease is characterized by anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life and, sometimes, early death.

Where adequate medical care is available, common treatments for patients with SCD largely revolve around management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced therapy for SCD is allogeneic hematopoietic stem cell transplantation (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft-versus-host disease, and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.

About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ BB305 product candidate, currently in four clinical studies for the treatment of transfusion-dependent ß-thalassemia and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in lentiviral gene delivery and T cell engineering, with a focus on developing novel T cell-based immunotherapies, including chimeric antigen receptor (CAR) and T cell receptor (TCR) therapies. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline.

bluebird bio has operations in Cambridge, Massachusetts and Seattle, Washington.

About AP-HP
AP-HP - Greater Paris University hospitals - is a European world-renowned university hospital. Its 39 hospitals treat 8 million people every year: in consultation, emergency, during scheduled or home hospitalizations. The AP-HP provides a public health service for everyone, 24 hours a day. This mission is a duty as well as a great source of pride. The AP-HP is the leading employer in the Greater Paris area: 100,000 staff members – doctors, researchers, paramedical staff, administrative personnel and workers – work there. http://www.aphp.fr

About the Imagine Institute
As the leading European center for research, care and teaching in genetic diseases, the Imagine Institute's primary aim is to understand and cure. The Institute's staff includes 850 of the best physicians, scientists and healthcare professionals housed in an innovative new building designed to realize synergies. This unprecedented continuum of expertise available in close proximity to patients allows Imagine to accelerate discoveries and their application at the bedside. www.institutimagine.org

Forward-Looking Statements
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s research and development plans for its LentiGlobin product candidate to treat severe sickle cell disease, including statements whether the manufacturing process changes for LentiGlobin will improve outcomes of patients with severe sickle cell disease and whether the planned changes to the HGB-206 clinical trial protocol will improve outcomes in patients with severe sickle cell disease. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin will not continue or be repeated in our ongoing, planned or expanded clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing process or the HGB-206 clinical trial protocol will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, and the risk that any one or more of our product candidates will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent quarterly report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.