From bluebird bio: FDA Accelerated Approval for SKYSONA® Gene Therapy for Early, Active Cerebral Adrenoleukodystrophy

FDA Approves bluebird bio Product Skysona for Early, Active CALD

SKYSONA is the first FDA approved therapy shown to slow the progression of neurologic dysfunction in boys with this devastating and fatal neurodegenerative disease.

The U.S. FDA has granted Accelerated Approval of bluebird bio’s (BLUE) SKYSONA® (elivaldogene autotemcel), also known as eli-cel.

SKYSONA® is indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD). It slowed the progression of neurologic dysfunction in boys 4 to 17 years old with early active CALD. 

The Product

SKYSONA® (elivaldogene autotemcel), also known as eli-cel is a one-time gene therapy custom-designed to treat the underlying cause of  CALD. SKYSONA uses ex-vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which can then participate in the local degradation of very long-chain fatty acids (VLCFAs).

This degradation of VLCFAs is believed to slow or possibly prevent further inflammation and demyelination.

From the Experts

Elisa Seeger, co-founder, ALD Alliance said that, “…the agony of watching your child slip away is something no parent should have to bear. We 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.”

David A. Williams, MD, Chief, Division of Hematology/Oncology, Boston Children’s Hospital, said, “CALD 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. After supporting the clinical development of SKYSONA for nearly a decade as a study site, Boston Children’s Hospital is extremely pleased that an FDA-approved therapy is now available for children who urgently need new therapies.”

Paul Orchard, MD, a pediatric blood and marrow transplant physician at the University of Minnesota Medical Schooland M Health Fairview Masonic Children’s Hospital, said, “As 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, It’s 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’ve seen firsthand the impact that gene therapy has on our patients.”

The Disease

CALD is a progressive and irreversible neurodegenerative disease that primarily affects young boys. The disorder is caused by mutations in the ABCD1 gene that affect the production of 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

CALD causes irreversible, devastating neurologic decline, including major functional disabilities, which include loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.  

Around half of patients who do not receive treatment die within five years of symptom onset. The good news about CALD is that it is a rare disease. 

Before the approval of SKYSONA, effective options were limited to allogeneic hematopoietic stem cell transplant (allo-HSCT). This treatment, though. has serious potential complications including death, which can dramatically increase in patients without a human leukocyte antigen (HLA) matched donor.

As 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.

bluebird 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’s Hospital and Children’s Hospital of Philadelphia

bluebird has set the wholesale acquisition cost of SKYSONA in the U.S. at $3.0 M.

Additional information is available through bluebird’s patient support program. My bluebird support provides personalized support for patients and their families related to all aspects of the gene therapy journey.

Caregivers of patients with CALD can call (833-888-6378) Monday-Friday between 8 a.m. and 8 p.m. ETto ask questions and enroll.

The 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.

The approval of bluebird bio Product, SKYSONA

The FDA approval is based on data from bluebird bio’s Phase 2/3 study ALD-102 (Starbeam) and Phase 3 ALD-104 study. Both 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.

Per 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 the loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.

The Accelerated Approval of SKYSONA

The accelerated approval is based on 24-month MFD-free survival. A post-hoc enrichment analysis in symptomatic patients assessed MFD-free survival from onset of symptoms in SKYSONA treated and untreated patients.

SKYSONA treated patients had an estimated 72 percent likelihood of MFD-free survival at 24 months from time of first NFS ≥ 1, compared to untreated patients who had only an estimated 43 percent likelihood of MFD-free survival.

The most common non-laboratory adverse reactions (incidence ≥ 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 (≥40%) include leukopenia, lymphopenia, thrombocytopenia, neutropenia, anemia, and hypokalemia. Please see SKYSONA Important Safety Information below, including a Boxed Warning for Hematologic Malignancy.

Enrollment 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.

Important to Know  

Important to learn safety Information and boxed warning about hematology malignancy. Also, important to learn about Serious Infections; Prolonged Cytopenias; serious adverse reactions of pancytopenia; Delayed Platelet Engraftment; Risk of Neutrophil Engraftment Failure; Hypersensitivity Reactions; Anti-retroviral Use; and other adverse reactions 

Bluebird bio

Founded in 2010, bluebird has the largest and deepest ex-vivo gene therapy data set in the world—setting the standard for 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. ​

SKYSONA and bluebird bio are trademarks of bluebird bio, Inc.

Prohost Observations

The approval of SKYSONA® is good news, not bad news.

In early morning today, following the approval news, BLUE soared. When the investors heard about the boxed warning, they caused a selloff, as if the approval of the drug was bad news for the firm and for its shareholders, which is completely irrelevant. CALD is an irreversible neurodegenerative disease that affects young boys; it tortures them and causes their deaths if they are not treated. Also, the physicians who treat them are trained to do the right thing when it comes to avoiding the adverse effects of the drug. Andrew Obenshain, Chief Executive Officer, bluebird bio, said, “…that for the ALD community, this long-awaited approval represents significant hope and offers families a new option.”

We are encouraged by the progress we’re making to treat these rare and devastating diseases.

Again, we state, that the approval of SKYSONA® is great news, not bad news.

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