Disease Stabilization Following Treatment with elivaldogene autotemcel (eli-cel, Lenti-D) Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy: Interim Results from Phase 2/3 (ALD-102) and Phase 3 (ALD-104) Studies (2064)

Objective: 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). Background: 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. Design/Methods: 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). Results: 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 The primary efficacy endpoint was met in 20/23 (87%) evaluable patients; 2 were withdrawn and 1 died after rapid disease progression and multiple MFDs.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). Conclusions: As of February 2020, 45 patients with CALD received eli-cel. The treatment showed a favorable benefit/risk profile with up to 71 months follow-up in ALD-102/LTF-304. Additional data will allow further insights into the clinical impact of eli-cel in CALD. Disclosure: An immediate family member of Dr. Eichler has received personal compensation for serving as an employee of UpToDate. Dr. Eichler has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for SwanBio Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Eichler has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Origin Biosciences. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Orchard Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Autobahn Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bluebird Bio. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. Dr. Eichler has received stock or an ownership interest from SwanBio Therapeutics. The institution of Dr. Eichler has received research support from Bluebird Bio. The institution of Dr. Eichler has received research support from Minoryx Therpeutics. Dr. Eichler has received intellectual property interests from a discovery or technology relating to health care. Christine Duncan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Advanced Clinical. Christine Duncan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Christine Duncan has received publishing royalties from a publication relating to health care. Paul Orchard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orchard Therapeutics. Paul Orchard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene. Paul Orchard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avrobio. Paul Orchard has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Satiro De Oliveira has received research support from Bluebird bio, inc. The institution of Satiro De Oliveira has received research support from Orchard Therapeutics. Caroline SEVIN has nothing to disclose. Harnan Amartino has nothing to disclose. Nicholas JC Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Nicholas JC Smith has received research support from Medical Research Futures Fund - Australia. Jorn-Sven Kuhl has nothing to disclose. Dr. Musolino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Minoryx Pharmaceuticals. Dr. Musolino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Altas Venture Capital. Dr. Musolino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Musolino has received research support from Minoryx Pharmaceuticals. Dr. Musolino has received research support from National Institute of Health-NINDS-R01. Dr. Musolino has received research support from Massachusetts General Hospital-ECOR. Dr. Musolino has received research support from Massachusetts General Hospital-Innovations Office. Dr. Musolino has received research support from National Institute of Health-NINDS-Admin Supp. K08. Dr. Musolino has received research support from Massachusetts General Hospital-Department of Neurology. Dr. Musolino has received research support from Dooley’s Family Fund. Dr. Musolino has received publishing royalties from a publication relating to health care. The institution of Dr. Kenney-Jung has received research support from CFC Foundation. The institution of Dr. Kenney-Jung has received research support from Advanced Medical Electronics/NIH. The institution of Dr. Kenney-Jung has received research support from Bluebird Bio. The institution of Dr. Kenney-Jung has received research support from Rare Disease Foundation. ROBERT CHIESA has nothing to disclose. Jean-Hugues Dalle has nothing to disclose. Andrew Dietz has received personal compensation for serving as an employee of bluebird bio, Inc.. Andrew Dietz has received stock or an ownership interest from bluebird bio, Inc. . Elizabeth D. McNeil has nothing to disclose. David Williams has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Emerging Therapy Solutions. David Williams has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Orchard Therapeutics. David Williams has received stock or an ownership interest from Orchard Therapeutics. David Williams has received research support from bluebird bio. David Williams has received publishing royalties from a publication relating to health care.