FDA Panel Votes in Favor of Gene Therapy for Cerebral Adrenoleukodystrophy

The Food and Drug Administration (FDA)’s Cellular, Tissue, and Gene Therapies Advisory Committee voted in favor of the approval of elivaldogene autotemcel (eli-cel) for the treatment of early active cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age who do not have an available and willing human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell (HSC) donor.

Cerebral adrenoleukodystrophy (CALD) is a rare, X-linked metabolic disorder caused by mutations in the ABCD1 gene, which affects the production of adrenoleukodystrophy protein (ALDP). Eli-cel is an investigational one-time gene therapy designed to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells, resulting in the production of ALDP.

The FDA panel’s recommendation is based on data from the phase 2/3 Starbeam study (ClinicalTrials.gov Identifier: NCT01896102), which evaluated the efficacy and safety of eli-cel in 32 patients with active CALD. The application also included data for 35 patients being evaluated in the phase 3 ALD-104 study (ClinicalTrials.gov Identifier: NCT03852498).

In clinical studies, there was a greater likelihood of both overall and event-free survival in patients treated with eli-cel compared with allo-HSCT patients without a matched sibling donor; the clearest benefit was observed for patients without a matched donor of any type. 

As for safety, the eli-cel clinical program was placed on a clinical hold in August 2021 due to a suspected unexpected serious adverse reaction of myelodysplastic syndrome (MDS). There were 2 subsequent cases of MDS reported. When asked if the benefits of eli-cel outweigh the risks, for the treatment of any subpopulation of children with early active CALD, the panel voted 15 yes, 0 no.

Although not bound by the panel’s recommendations, the FDA does take them into consideration when making decisions on approval. A Prescription Drug User Fee Act (PDUFA) target date of September 16, 2022 has been set for the application. The FDA previously granted Priority Review, Orphan Drug, Rare Pediatric Disease, and Breakthrough Therapy designations to eli-cel for this indication.

Reference

FDA advisory committee unanimously endorses eli-cel gene therapy for cerebral adrenoleukodystrophy. News release. bluebird bio, Inc. June 9, 2022. Accessed June 10, 2022. https://www.businesswire.com/news/home/20220609006060/en/FDA-Advisory-Committee-Unanimously-Endorses-eli-cel-Gene-Therapy-for-Cerebral-Adrenoleukodystrophy