FDA Fast Tracks Approval of Novel Therapy for Rare Neurologic Disorder

Megan Brooks


September 19, 2022

The US Food and Drug Administration (FDA) has granted accelerated approval to the novel gene therapy elivaldogene autotemcel (Skysona, bluebird bio) for the treatment of cerebral adrenoleukodystrophy (CALD).

The therapy "is indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age" with early, active CALD, the manufacturer noted in a press release.

CALD is a rare, progressive, neurodegenerative disease that mostly affects young boys and causes irreversible neurologic decline, including major functional disabilities such as loss of communication, cortical blindness, need for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.

The approval follows a unanimous thumbs up for the therapy by an FDA advisory committee in June, as reported by Medscape Medical News.

Until now, effective options for CALD were limited to allogeneic hematopoietic stem cell transplant, which carries the risk of serious complications including treatment-related death, graft failure, and graft versus host disease.

"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," Elisa Seeger, co-founder of the ALD Alliance, said in the release.

With this approval, "parents whose boys receive a CALD diagnosis can have renewed hope for the future," Seeger added.

"Urgently Needed"

The neurologic disorder is caused by mutations in the ABCD1 gene. Elivaldogene autotemcel works by leveraging ex vivo transduction with a lentiviral vector to insert functional copies of the ABCD1 gene into a patient's hematopoietic stem cells.

Results from a phase 2/3 study showed 2 years after receiving a single treatment with the gene therapy, there was no deterioration of neurologic function in 27 of 30 boys (90%) with early active CALD, according to data reported last year at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.

The most common nonlaboratory adverse reactions include 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 include leukopenia, lymphopenia, thrombocytopenia, neutropenia, anemia, and hypokalemia.

Elivaldogene autotemcel had breakthrough therapy and orphan drug status and received priority review.

As a condition of accelerated approval, the company will provide confirmatory long-term clinical data to the FDA. 

The company expects elivaldogene autotemcel to be available by the end of this year through a limited number of qualified treatment centers in the United States, including Boston Children's Hospital and Children's Hospital of Philadelphia, which participated in clinical testing.

"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," David A. Williams, MD, chief, division of hematology/oncology, Boston Children's Hospital, said in the release.

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