BLA submission based on data from the largest and most mature clinical development program for any gene therapy in sickle cell disease

PDUFA date set for December 20, 2023

bluebird bio, Inc. (Nasdaq: BLUE) today announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for lovotibeglogene autotemcel (lovo-cel) for priority review. Lovo-cel is a potentially transformative one-time gene therapy for individuals living with sickle cell disease (SCD) ages 12 and older who have a history of vaso-occlusive events (VOEs). It is specifically designed to treat the underlying cause of SCD through the addition of a functional gene that enables production of anti-sickling adult hemoglobin and is the most deeply studied gene therapy in development for this disease. The agency has set a Prescription Drug User Fee Act (PDUFA) goal date of December 20, 2023.

“The burden that people living with SCD and their families live with today is staggering. Beyond extreme pain crises that send patients to the hospital, SCD progression is associated with grave long-term consequences,” said Andrew Obenshain, chief executive officer, bluebird bio. “The FDA’s acceptance of our BLA for lovo-cel moves us one step closer in bringing a potentially transformative therapy to the sickle cell disease community that is long overdue, and we are grateful to the patients, caregivers, researchers, clinicians, and community leaders who have enabled this exciting milestone. We look forward to working with the agency on its review.”

The BLA for lovo-cel is based on efficacy results from 36 patients in the HGB-206 study Group C cohort with a median 32 months of follow-up and two patients in the HGB-210 study with 18 months of follow-up each. The BLA submission also includes safety data from 50 patients treated across the entire lovo-cel program, including six patients with six or more years of follow-up, which is the longest follow-up of any gene therapy program for SCD.

If approved, lovo-cel will be bluebird bio’s third ex-vivo gene therapy approved by the FDA for a rare genetic disease and its second FDA approval for an inherited hemoglobin disorder, building on more than a decade of leadership in gene therapy.

The FDA’s Priority Review designation is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions, and targets a review timeline of six months from the time of filing, compared to a standard review timeline of 10 months.

The FDA previously granted lovo-cel orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation, and rare pediatric disease designation.

About sickle cell disease (SCD)

Sickle cell disease (SCD) is a complex and progressive genetic disease associated with debilitating and unpredictable pain crises, anemia, irreversible damage to vital organs, and early death. In SCD, high concentrations of sickle hemoglobin (HbS) in red blood cells (RBCs) cause RBCs to become sickled, sticky, and rigid with a shorter life span, which manifests acutely as hemolytic anemia, vasculopathy, and vaso-occlusion. Pain onset can be sudden and unpredictable, often requiring hospitalization. Fifty to sixty percent of adults with sickle cell disease have end organ damage, with 24 percent experiencing damage in multiple organs, and one in four patients have a stroke by the age of 45. The impact of SCD is pervasive and affects every aspect of life for patients and their families and caregivers – from missed work and school, decreased quality of life and mental health, and the ability to complete daily tasks. In the U.S., there are approximately 100,000 people living with SCD, and the median age of death is 45 years of age.

While SCD was the first disease to have a genetic cause identified, treatment advances have lagged – since that discovery in 1949,ⁱ only four therapies have been approved,ⁱⁱ none of which address the underlying genetic cause of disease.

About lovotibeglogene autotemcel (lovo-cel)

lovotibeglogene autotemcel (lovo-cel) gene therapy is an investigational one-time treatment being studied for sickle cell disease (SCD), that is designed to add functional copies of a modified form of the β-globin gene (β^A-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the β^A-T87Q-globin gene, their red blood cells (RBCs) can produce anti-sickling hemoglobin (HbA^T87Q) that decreases the proportion of HbS, with the goal of reducing sickled RBCs, hemolysis, and other complications. bluebird bio’s clinical development program for lovo-cel includes the completed Phase 1/2 HGB-205 and ongoing Phase 1/2 HGB-206 and Phase 3 HGB-210 studies. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have been treated with lovo-cel in bluebird bio-sponsored clinical studies.

In the BLA submission, as of August 2022, the majority of adverse events in treated patients were attributed to underlying sickle cell disease or conditioning with busulfan. Nonserious adverse events related to lovo-cel included infusion reactions (hot flush and decreased blood pressure) in two patients (2% each). Serious adverse events related to lovo-cel included anemia in two patients (4%) with concurrent alpha-thalassemia trait, and leukemia in two patients (4%), not resulting from insertional oncogenesis. Three of 50 patients (6%) died, one due to sudden cardiac death and two due to leukemia.

About bluebird bio, Inc.

bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days.

With a dedicated focus on severe genetic diseases, bluebird has industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy and is advancing research to apply new technologies to these and other diseases. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward.

Founded in 2010, bluebird has the largest and deepest ex-vivo gene therapy data set in the world—setting the standard for the industry. Today, bluebird continues to forge new paths, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds.

For more information, visit bluebirdbio.com or follow us on social media at @bluebirdbio, LinkedIn, Instagram and YouTube.

bluebird bio is a trademark of bluebird bio, Inc.

Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, including, without limitation, our statements regarding: the therapeutic potential of lovo-cel, including its potential as a transformative therapy for the sickle cell disease community; the possible approval of lovo-cel by FDA and the expected timing relating to such regulatory approval, including the shortened FDA review period for therapies designated for Priority Review; and bluebird bio’s ability to pursue creative gene therapies to give patients and their families more bluebird days. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. These risks include, but are not limited to: delays and challenges in obtaining regulatory approval of our product candidates and our commercialization and manufacturing of our products, including risks associated with demonstrating analytical comparability with respect to our lovo-cel program; we may encounter additional delays in the development of our programs, including the imposition of new clinical holds, that may impact our ability to meet our expected timelines and increase our costs; the internal and external costs required for our ongoing and planned activities, and the resulting impact on expense and use of cash, has been, and may in the future be, higher than expected, which has caused us, and may in the future cause us to use cash more quickly than we expect or change or curtail some of our plans or both; our expectations as to expenses, cash usage and cash needs may prove not to be correct for other reasons such as changes in plans or actual events being different from our assumptions; the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be seen in additional patients treated with our product candidates; the risk that additional insertional oncogenic or other reportable events associated with lentiviral vector, drug product, or myeloablation will be discovered or reported over time; the risk that our eli-cel, beti-cel and lovo-cel programs may be subject to further delays in their development, including but not limited to the imposition of new clinical holds; the risk that any one or more of our products or product candidates, including eli-cel and, beti-cel or lovo-cel, will not be successfully developed, approved or commercialized, as applicable. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, bluebird bio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

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ⁱ Pauling L, Itano HA, Singer SJ, Wells IC. Sickle cell anemia, a molecular disease. Science. 1949;110(2865):543-548. doi:10.1126/science.110.2865.543.

ⁱⁱ Rai P, Ataga KI. Drug Therapies for the Management of Sickle Cell Disease. F1000Res. 2020 Jun 11;9:F1000 Faculty Rev-592. doi: 10.12688/f1000research.22433.1. PMID: 32765834; PMCID: PMC7388199.

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