New Gene Therapy Beneficial for Adolescent Patients with Cerebral Adrenoleukodystrophy


The investigators found the primary efficacy endpoints occurred in 20 evaluable patients (87%).

Paul Orchard, MD

Paul Orchard, MD

A gene therapy dubbed eli-cel is showing a favorable safety and efficacy profile in initial trials for adolescents with cerebral adrenoleukodystrophy (CALD).

A team, led by Paul J. Orchard, MD, University of Minnesota Children’s Hospital, updated the results from the initial ALD-102 study data with fully enrolled patient data investigating the alternative myeloablative protocol utilizing busulfan/fludarabine in lieu of busulfan/cyclophosphamide.

In the ALD-102 study, researchers previously found elivaldogene autotemcel gene therapy resulted in 88% of patients with cerebral adrenoleukodystrophy met the primary endpoint of survival free of major functional disabilities at 24 months.

In the study, male adolescents with cerebral adrenoleukodystrophy underwent hematopoietic stem cells mobilization with granulocyte colony-stimulating factor +/- plerixafor, followed by apheresis collection.

Following conditioning, the patients received eli-cel (autologous CD34+ HSCs transduced with Lenti-D lentiviral vector encoding ABCD1 cDNA) and after ALD-102/ALD-104 (2 years), monitoring continues for an additional 13 years in LTF-304.

There was follow-up data for 32 patients treated in the study as of January 2020, totaling 30.0 months.

Promising Results

The investigators found the primary efficacy endpoints occurred in 20 evaluable patients (87%). For the remaining 3 patients, 2 withdrew from the study and 1 died after rapid disease progression and multiple major functional disabilities.

In addition, 20 patients completed ALD-102 and were enrolled in LTF-304, while 9 additional patients—with a max follow-up of 22.1 months—were still in ALD-102. There were no major functional disabilities in this entire subgroup of patients.

As of February 2020, 13 patients received eli-cel in ALD-104. This group had a median of 6.1 months of follow-up. A total of 32 ALD-102 patients achieved neutrophil engraftment in 13 days (11-41), while 13 ALD-104 patients achieved neutrophil engraftment in 13 days (12-31).

Adverse Events

Platelet engraftment (PE) occurred in 32 days (16-60) in ALD-102 (n = 32) and 27 days (18-108) in ALD-104 (n = 12).

However, 2 patients in ALD-104 had ongoing severe adverse events of pancytopenia—considered possibly eli-cel-related. In this group, 1 patients with PE on day 107 and the other pending an additional platelet value to confirm PE on day 104.

However, these severe adverse events did not meet the criteria for failed engraftment and were considered clinically stable.

The researchers also observed an additional ongoing severe adverse event of transverse myelitis, which was unrelated to eli-cel and partially responsive to steroids or plasmapheresis.

For ALD-102, there were 3 adverse events potentially related to eli-cell—1 BK viral cystitis and 2 cases of vomiting.

The treatment regimen in the eli-cel studies had a safety and tolerability profile generally reflective of the known effects of mobilization and apheresis and conditioning with no graft failure, graft-versus-host disease, replication competent lentivirus or insertional oncogenesis.

The researchers observed benign clonal expansion in 1 ALD-102 patient who was clinically well as of last March.

“As of February 2020, 45 boys with CALD received eli-cel,” the authors wrote. “The treatment showed a favorable benefit/risk profile with up to 71 months follow-up in ALD-102/LTF-304. Additional data from ALD-102/LTF-304 and ALD-104 will allow further insights into the clinical impact of eli-cel in CALD.”

The study, “Elivaldogene Autotemcel (eli-cel, Lenti-D) Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy: Updated Results from the Phase 2/3 ALD-102 Study and First Report on Safety Outcomes from the Phase 3 ALD-104 Study,” was published online by TCT.

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