Eli-Cel Gene Therapy for CALD Is Granted Priority Review


The program is still on clinical hold following SUSARs of myelodysplastic syndrome in treated participants.

bluebird bio’s biologics license application (BLA) for elivaldogene autotemcel (Skysona; eli-cel, Lenti-D®), a gene therapy for the potential treatment of cerebral adrenoleukodystrophy (CALD) in pediatric patients, has been granted priority review by the FDA. The Prescription Drug User Fee Act (PDUFA) date is set for June 17, 2022.1

“Eli-cel is an important potential therapeutic option for patients with CALD—a devastating neurodegenerative disease—and we are encouraged to be moving forward given the urgent unmet need for these children and their families,” Andrew Obenshain, chief executive officer, bluebird bio, said in a statement.1 

The BLA is based on efficacy and safety data from 32 participants in the completed Phase 2/3 Starbeam study (ALD-102; NCT01896102) and 23 participants in the Phase 3 ALD-104 study (NCT03852498), in which follow-up is ongoing. An additional long-term follow-up study (LTF-304; NCT02698579) is ongoing.

The primary end point of the Starbeam study was Major Functional Disabilities (MFD)-free survival at 24 months, of which 29 patients (90.6%) met. Two participants withdrew at investigator discretion and 1 participant experienced rapid disease progression, MFD, and death. Median follow-up, including in the long-term follow-up study, is 3.5 years (42.3 months; range, 13.4-83.7).

Participants experienced adverse events including myelodysplastic syndrome (MDS), cystitis viral, pancytopenia, and vomiting. No instances of graft-versus-host-disease, graft failure or rejection, transplant-related mortality, or replication competent lentivirus have been reported.

Eli-cel was placed on clinical hold by the FDA in August 2021 following the Suspected Unexpected Serious Adverse Reaction (SUSAR) of MDS in the ALD-104 study thought to be mediated by the use of their lentiviral vector.2 Two other cases of MDS have been reported in participants treated with eli-cel and the clinical hold is ongoing, with treated participants being closely monitored.

bluebird withdrew its EU marketing authorization and UK filing for eli-cel in October 2021 and plans to do the same with betibeglogene autotemcel (beti-cel) by early 2022 following ongoing challenges with regulators over pricing and marketing disputes. The company is restructuring to focus on US markets.3

The FDA previously granted eli-cel orphan drug status, rare pediatric disease designation, and breakthrough therapy designation. 

In September 2021, bluebird submitted a BLA for beti-cel for the potential treatment of patients with β-thalassemia who require regular red blood cell transfusions, based on data from 2 phase 3 studies (NCT03207009 and NCT02906202) evaluating the therapy across all phenotypes as well as a previous phase 1/2 study (NCT01745120).4 The application was accepted, with a PDUFA date of May 20, 2022.

According to long-term data from the LTF-303 trial (NCT02633943) presented at the 2021 ASH Annual Meeting and Exposition, treatment with beti-cel produced normal or near-normal levels of total hemoglobin in 3 transfusion-dependent patients with β-thalassemia, who continue to remain transfusion-free and achieve stable iron markers through up to 7years of follow-up.5

“As the second BLA acceptance for bluebird bio this year, this is a meaningful milestone in our work to deliver one-time treatments for severe genetic diseases,” Obenshain added to the statement.1

1. bluebird bio announces FDA priority review of biologics license application for eli-cel gene therapy for cerebral adrenoleukodystrophy (CALD) in patients without a matched sibling donor. News release. bluebird bio. December 17, 2021. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-fda-priority-review-biologics-license-0
2. bluebird bio reports second quarter financial results and provides operational update. News release. bluebird bio. August 9, 2021. https://www.businesswire.com/news/home/20210809005334/en/bluebird-bio-Reports-Second-Quarter-Financial-Results-and-Provides-Operational-Update
3. Bluebird to withdraw Zynteglo from Germany after price negotiations failed to recognize drug’s value. News release. April 24, 2021. Accessed August 10, 2021. https://www.eversana.com/2021/04/21/bluebird-to-withdraw-zynteglo-from-germany-after-price-negotiations-failed-to-recognize-drugs-value/
4. bluebird bio submits biologics license application (BLA) to FDA for betibeglogene autotemcel (beti-cel) gene therapy for patients with β-thalassemia who require regular red blood cell transfusions. News release. bluebird bio. September 21, 2021. https://www.businesswire.com/news/home/20210921005978/en/bluebird-bio-Submits-Biologics-License-Application-BLA-to-FDA-for-betibeglogene-autotemcel-beti-cel-Gene-Therapy-for-Patients-With-%CE%B2-thalassemia-Who-Require-Regular-Red-Blood-Cell-Transfusions
5. Thompson AA, Locatelli F, Yannaki E, et al. Restoring Iron Homeostasis in Pts Who Achieved Transfusion Independence after Treatment with Betibeglogene Autotemcel Gene Therapy: Results from up to 7 Years of Follow-up. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 573.
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