{"id":48519,"date":"2022-09-17T06:01:48","date_gmt":"2022-09-17T04:01:48","guid":{"rendered":"https:\/\/pharma-trend.com\/en\/bluebird-bio-receives-fda-accelerated-approval-for-skysona-gene-therapy-for-early-active-cerebral-adrenoleukodystrophy-cald\/"},"modified":"2022-09-17T06:01:48","modified_gmt":"2022-09-17T04:01:48","slug":"bluebird-bio-receives-fda-accelerated-approval-for-skysona-gene-therapy-for-early-active-cerebral-adrenoleukodystrophy-cald","status":"publish","type":"post","link":"https:\/\/pharma-trend.com\/en\/bluebird-bio-receives-fda-accelerated-approval-for-skysona-gene-therapy-for-early-active-cerebral-adrenoleukodystrophy-cald\/","title":{"rendered":"bluebird bio Receives FDA Accelerated Approval for SKYSONA\u00ae Gene Therapy for Early, Active Cerebral Adrenoleukodystrophy (CALD)"},"content":{"rendered":"
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\nSKYSONA is the first FDA approved therapy shown to slow the progression of neurologic dysfunction in boys with this devastating and fatal neurodegenerative disease<\/i>\n<\/p>\n

\nManagement team to host conference call <\/i>Monday, September 19, at 8:00 a.m. ET<\/i>\n<\/p>\n

SOMERVILLE, Mass.–(BUSINESS WIRE)–bluebird bio, Inc. (Nasdaq: BLUE) today announced the U.S. Food and Drug Administration (FDA) has granted Accelerated Approval of SKYSONA\u00ae (elivaldogene autotemcel), also known as eli-cel, to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD). The Company also confirmed that the previous clinical hold on the eli-cel clinical development program has been lifted.\n<\/p>\n

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\nCALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes irreversible, devastating neurologic decline, including major functional disabilities such as loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement. Nearly half of patients who do not receive treatment die within five years of symptom onset. Prior to the approval of SKYSONA treatment, effective options were limited to allogeneic hematopoietic stem cell transplant (allo-HSCT), which is associated with the risk of serious potential complications including death, that can increase dramatically in patients without a human leukocyte antigen (HLA) matched donor.\n<\/p>\n

\n\u201cChildren with CALD and their families have been at the heart of bluebird\u2019s mission since the company was founded more than a decade ago,\u201d said Andrew Obenshain, chief executive officer, bluebird bio. \u201cFor the ALD community, this long-awaited approval represents significant hope and offers families a new option where, for many, there had been none. We are grateful to every individual who was involved in the development of SKYSONA and are committed to working with providers and payers to make this important treatment option available to patients and their families.\u201d\n<\/p>\n

\n\u201cThe agony of watching your child slip away is something no parent should have to bear,\u201d said Elisa Seeger, co-founder, ALD Alliance. \u201cWe have made significant strides in providing children diagnosed with CALD the best chance at life with early identification of ALD through expanded newborn screening. Yet with limited treatment options, early diagnosis is still cause for despair instead of hope for many families. Today, parents whose boys receive a CALD diagnosis can have renewed hope for the future.\u201d\n<\/p>\n

\n\u201cCALD strikes young boys in the prime of their development, robbing them of core neurologic functions necessary for survival. That is an unimaginable reality for any parent, and as a clinician, it is heartbreaking to have limited treatment options for these children and their families,\u201d said David A. Williams, MD, Chief, Division of Hematology\/Oncology, Boston Children\u2019s Hospitali<\/sup>. \u201cAfter supporting the clinical development of SKYSONA for nearly a decade as a study site, Boston Children\u2019s Hospital is extremely pleased that an FDA-approved therapy is now available for children who urgently need new therapies.\u201d\n<\/p>\n

\n\u201cAs one of the largest and most experienced pediatric gene therapy and stem cell transplant programs in the world, the University of Minnesota is committed to expanding access and advancing care and research for patients with rare diseases like ALD,\u201d said Paul Orchard, MD, a pediatric blood and marrow transplant physician at the University of Minnesota Medical School and M Health Fairview Masonic Children\u2019s Hospital. \u201cIt\u2019s crucial for these patients and families to have another therapeutic option for cerebral ALD beyond blood stem cell transplantation utilizing cells from another donor, and we\u2019ve seen firsthand the impact that gene therapy has on our patients. We are encouraged by progress we\u2019re making to treat these rare and devastating diseases.\u201d\n<\/p>\n

\nAs a condition of the SKYSONA Accelerated Approval, bluebird has agreed to provide confirmatory long-term clinical data to the FDA. bluebird anticipates that this will include data from the ongoing long-term follow-up study (LTF-304), which follows patients treated in clinical trials for 15 years, and from commercially treated patients.\n<\/p>\n

\nbluebird anticipates that commercial product will be available by the end of 2022 through a limited number of Qualified Treatment Centers (QTCs) in the United States, including Boston Children\u2019s Hospital and Children\u2019s Hospital of Philadelphia.\n<\/p>\n

\nbluebird has set the wholesale acquisition cost of SKYSONA in the U.S. at $3.0M. Additional information is available through bluebird\u2019s patient support program, my bluebird support<\/i>, which will provide personalized support for patients and their families related to all aspects of the gene therapy journey. Caregivers of patients with CALD can visit mybluebirdsupport.com or call 833-888-NEST (833-888-6378) Monday-Friday between 8 a.m. and 8 p.m. ET to ask questions and enroll.\n<\/p>\n

\nThe SKYSONA Biologics License Application (BLA) was reviewed by the U.S. FDA under Priority Review, and bluebird received a rare pediatric priority review voucher upon approval. SKYSONA was previously granted Orphan Drug designation, Rare Pediatric Disease designation, and Breakthrough Therapy designation.\n<\/p>\n

\nSKYSONA Clinical Data<\/b>\n<\/p>\n

\nThe approval of SKYSONA is based on data from bluebird bio\u2019s Phase 2\/3 study ALD-102 (Starbeam) (N=32) and Phase 3 ALD-104 (N=35) study.\n<\/p>\n

\nBoth open-label, single-arm studies enrolled patients with early, active CALD who had elevated very long chain fatty acid (VLCFA) values, a Loes score between 0.5 and 9 (inclusive), and gadolinium enhancement on magnetic resonance imaging (MRI) of demyelinating lesions. Additionally, patients were required to have a neurologic function score (NFS) of \u2264 1, indicating limited changes in neurologic function. The efficacy of SKYSONA was compared to a natural history population.\n<\/p>\n

\nPer protocol, patients treated with SKYSONA were assessed using the NFS and monitored for the emergence of six Major Functional Disabilities (MFDs) associated with CALD progression including loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.\n<\/p>\n

\nThe Accelerated Approval of SKYSONA is based on 24-month MFD-free survival. A post-hoc enrichment analysis in symptomatic patients assessed MFD-free survival from onset of symptoms (NFS \u2265 1) in SKYSONA treated (N=11) and untreated patients (N=7). SKYSONA treated patients had an estimated 72 percent likelihood of MFD-free survival at 24 months from time of first NFS \u2265 1, compared to untreated patients who had only an estimated 43 percent likelihood of MFD-free survival.\n<\/p>\n

\nThe most common non-laboratory adverse reactions (incidence \u2265 20%) are mucositis, nausea, vomiting, febrile neutropenia, alopecia, decreased appetite, abdominal pain, constipation, pyrexia, diarrhea, headache, and rash. The most common Grade 3 or 4 laboratory abnormalities (\u226540%) include leukopenia, lymphopenia, thrombocytopenia, neutropenia, anemia, and hypokalemia. Please see SKYSONA Important Safety Information below, including a Boxed Warning<\/b> for Hematologic Malignancy.\n<\/p>\n

\nEnrollment is complete and all patients have been treated in both studies; follow-up in ALD-104 is ongoing. All patients who complete 24 months of follow-up in studies ALD-102 or ALD-104 are encouraged to participate in a long-term follow-up study (LTF-304) to continue monitoring safety and efficacy outcomes in boys treated with SKYSONA through 15 years post-treatment. On September 15, 2022, the FDA lifted the clinical hold that was put in place August 2021, prior to the completion of its review of the SKYSONA Biologics License Application.\n<\/p>\n

\nAbout Cerebral Adrenoleukodystrophy (CALD)<\/b>\n<\/p>\n

\nCALD is a progressive and irreversible neurodegenerative disease that primarily affects young boys. The disorder is caused by mutations in the ABCD1<\/i> gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently leads to accumulation of very long-chain fatty acids (VLCFAs), primarily in the white matter of the brain and spinal cord. This accumulation leads to the breakdown of myelin, the protective sheath that nerve cells need to function effectively, especially for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7). Early diagnosis and treatment of CALD is essential, as nearly half of patients who do not receive treatment die within five years of symptom onset.\n<\/p>\n

\nIndication<\/b>\n<\/p>\n

\nSKYSONA is indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD). Early, active cerebral adrenoleukodystrophy refers to asymptomatic or mildly symptomatic (neurologic function score, NFS \u2264 1) boys who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9.\n<\/p>\n

\nThis indication is approved under accelerated approval based on 24-month Major Functional Disability (MFD)- free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).\n<\/p>\n

\nLimitations of Use<\/span>\n<\/p>\n

\nSKYSONA does not prevent the development of or treat adrenal insufficiency due to adrenoleukodystrophy.\n<\/p>\n

\nAn immune response to SKYSONA may limit the persistence of descendent cells of SKYSONA, causing rapid loss of efficacy of SKYSONA in patients with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 (ABCD1) transgene.\n<\/p>\n

\nSKYSONA has not been studied in patients with CALD secondary to head trauma.\n<\/p>\n

\nGiven the risk of hematologic malignancy with SKYSONA, and unclear long-term durability of SKYSONA and human adrenoleukodystrophy protein (ALDP) expression, careful consideration should be given to the appropriateness and timing of treatment for each boy, especially for boys with isolated pyramidal tract disease based on available treatment options since their clinical symptoms do not usually occur until adulthood.\n<\/p>\n

\nImportant Safety Information<\/b>\n<\/p>\n

\nBOXED WARNING: HEMATOLOGIC MALIGNANCY<\/b>\n<\/p>\n

\nHematologic malignancy, including life-threatening cases of myelodysplastic syndrome, has occurred in patients treated with SKYSONA. Patients have been diagnosed between 14 months and 7.5 years after SKYSONA administration, and the cancers appear to be the result of the SKYSONA lentiviral vector, Lenti-D, integration in proto-oncogenes. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through assessments for evidence for clonal expansion or predominance at least twice in the first year and annually thereafter; consider bone marrow evaluations as clinically indicated.<\/b>\n<\/p>\n

\nHematologic Malignancy<\/b>\n<\/p>\n

\nMyelodysplastic syndrome (MDS), a hematologic malignancy, has developed in patients treated with SKYSONA in clinical studies. At the time of initial product approval, MDS had been diagnosed in three patients after administration of SKYSONA. The clinical presentation for the three patients varied. Two patients who were diagnosed at 14 months and 2 years after treatment with SKYSONA had preceding delayed platelet engraftment. The third patient had normal blood counts from 18 months to 5 years following treatment with SKYSONA and presented 7.5 years after SKYSONA administration with symptomatic anemia and thrombocytopenia and was subsequently diagnosed with MDS with increased blasts. All 3 patients underwent allogeneic hematopoietic stem cell transplant; 1 patient required pre-transplant chemotherapy and total body irradiation as treatment for excess blasts prior to transplant and 1 patient underwent total body irradiation as part of his conditioning regimen.\n<\/p>\n

\nSKYSONA Lenti-D lentiviral vector integration into proto-oncogenes appears to have mediated the three cases of hematologic malignancy. The hematologic malignancies diagnosed at 14 months and 2 years involved integration into the MECOM<\/i> proto-oncogene and increased expression of the oncoprotein EVI1. All patients treated with SKYSONA in clinical studies have integrations into MECOM<\/i>; it is unknown which integrations into MECOM<\/i> or other proto-oncogenes are likely to lead to malignancy.\n<\/p>\n

\nBecause of the risk of hematologic malignancy, carefully consider alternative therapies prior to the decision to treat a child with SKYSONA. Consider consultation with hematology experts prior to SKYSONA treatment to inform benefit-risk treatment decision and to ensure adequate monitoring for hematologic malignancy. Consider performing the following baseline hematologic assessments: complete blood count with differential, hematopathology review of peripheral blood smear, and bone marrow biopsy (core and aspirate) with flow cytometry, conventional karyotyping, and next generation sequencing (NGS) with a molecular panel appropriate for age and including coverage for gene mutations expected in myeloid and lymphoid malignancies; and testing for germline mutations that are associated with hematologic malignancy.\n<\/p>\n

\nEarly diagnosis of hematologic malignancy can be critically important, therefore, monitor patients treated with SKYSONA lifelong for hematologic malignancy. For the first fifteen years after treatment with SKYSONA, monitor via complete blood count (with differential) at least twice per year and via integration site analysis or other testing for evidence of clonal expansion and predominance at least twice in the first year and then annually. Consider appropriate expert consultation and additional testing such as more frequent complete blood count (with differential) and integration site analysis, bone marrow studies, and gene expression studies in the following settings after treatment with SKYSONA:\n<\/p>\n