To provide updates on the fully enrolled ALD-102 study of elivaldogene autotemcel (eli-cel; Lenti-D) gene therapy and preliminary data from the ALD-104 study investigating an alternative myeloablative protocol (busulfan/fludarabine instead of busulfan/cyclophosphamide).

Earlier ALD-102 results showed 88% of patients with cerebral adrenoleukodystrophy (CALD) met the primary endpoint of survival free of major functional disabilities (MFD) at 24 months.

Post-conditioning, boys with CALD (≤17 years) received eli-cel (autologous CD34+ cells transduced with Lenti-D lentiviral vector encoding ABCD1 cDNA). After ALD-102/ALD-104 (2 years), monitoring continues in LTF-304 (13 years). Data are median (min?max).

As of January 2020, 32 ALD-102/LTF-304 patients had 30.0 (9.1–70.7) months follow-up. The primary efficacy endpoint was met in 20/23 (87%) evaluable patients; 2 were withdrawn and 1 died after rapid disease progression and multiple MFDs. Twenty patients transitioned to LTF-304 and 9 were still in ALD-102 (maximum follow-up 22.1 months); all without MFDs. At last visit, 31/32 patients had stable neurologic function scores; gadolinium enhancement resolved in 28/32 patients.

As of February 2020, 13 ALD-104 patients had reached 6.1 (2.2–10.3) months follow-up. All 13 patients achieved neutrophil and 12/13 platelet engraftment (one was pending engraftment on d104).

In eli-cel studies, the safety/tolerability profile has been primarily reflective of the known effects of mobilization/apheresis and conditioning. In ALD-104, 3 SAEs were ongoing: pancytopenia (n=2; possibly eli-cel-related; both patients clinically stable) and transverse myelitis (n=1; unknown etiology; partially responsive to steroids/plasmapheresis). There was no graft failure, graft-versus-host disease, replication competent lentivirus, or insertional oncogenesis. One ALD-102 patient with benign clonal expansion was clinically well at last visit (Month 62, March 2020).