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Abstract Details

Interim Results from the NEXUS Open-Label Registration Study on the Safety and Efficacy of Leriglitazone in the Treatment of Childhood Cerebral Adrenoleukodystrophy
Child Neurology and Developmental Neurology
ES2 - Emerging Science 2 (5:36 PM-5:42 PM)
002

cALD is a rapidly fatal, X-linked neurodegenerative disorder characterized by inflammatory brain demyelination. Allogeneic and autologous hematopoietic stem cell transplantation (HSCT) may halt disease progression, but there is an unmet need for less invasive therapies that can be administered immediately upon lesion identification. Leriglitazone is a peroxisome proliferator-activated receptor γ agonist with potential for treating adrenoleukodystrophy.

To assess 24-week safety, efficacy and study continuation criteria in boys with cerebral adrenoleukodystrophy (cALD) treated with leriglitazone.

This 96-week, open-label, multicenter study for European registration (NEXUS; NCT04528706) of once-daily oral leriglitazone has enrolled 17 boys (target: 13) 2–12 years old with cALD with or without gadolinium-enhancing lesions. The primary endpoint is the proportion of patients with clinically and radiologically arrested disease at week 96 (success criteria: one-sided 95% confidence interval [CI] > 10%). We present a prespecified 24-week interim analysis, including assessment of study continuation criteria (≥ 4/13 patients with arrested disease or lesion growth deceleration without clinical progression). Secondary endpoints include change from baseline in neurological function score (NFS) and Loes score (LS). Change from baseline in plasma biomarker concentrations is an exploratory endpoint.

Eleven patients were evaluable at week 24. Continuation criteria were met: all patients demonstrated lesion growth deceleration. All remained clinically stable (free of major functional disability and stable NFS). Five patients had arrested disease (45.5%, 95% CI: 13.9–68.4%). Median (range) change from baseline was 0.0 (0.0–1.0) for NFS and 0.0 (0.0–3.0) for LS. Neurofilament light chain concentrations stabilized in most patients. Matrix metalloproteinase-9 concentrations decreased in all patients. There were no severe adverse events, treatment-related serious adverse events or deaths.

Leriglitazone was well tolerated, continuation criteria were met, and disease arrest or stabilization was demonstrated radiologically, clinically and via plasma biomarkers. LS changes were similar to those attained with HSCT-based therapies. Enrolment is ongoing. 

Authors/Disclosures
Eric James Mallack, MD (New York Presbyterian Hospital, Cornell, Child Neurology)
PRESENTER
The institution of Dr. Mallack has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Grace Science. The institution of Dr. Mallack has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lysogene. Dr. Mallack has received research support from NINDS.
Angeles Garcia-Cazorla, MD,PhD (Hospital Sant Joan de Déu) Dr. Garcia-Cazorla has nothing to disclose.
Juliana Ribeiro Constante, MD (HSJD) Ms. Constante has nothing to disclose.
Caroline Sevin Caroline Sevin has nothing to disclose.
Elise Yazbeck, MD (ICM (Institut du Cerveau et de la Moelle Epinière)) Dr. Yazbeck has nothing to disclose.
Hendrik Rosewich, MD (University Medicine Göttingen) The institution of Prof. Rosewich has received research support from German Research Council. The institution of Prof. Rosewich has received research support from Eva Luise und Horst Köhler Stiftung.
Sandra Liliana Jimenez, MD (Hasbro Children's Hospital) Dr. Jimenez has nothing to disclose.
Gloria Chiang The institution of Gloria Chiang has received research support from NIH/NIA. Gloria Chiang has received research support from Minoryx. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker for CME with Horizons CME. Gloria Chiang has received personal compensation in the range of $5,000-$9,999 for serving as a Invited Speaker for CME with Efficient CME. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Taiwan Neuroradiological Society. Gloria Chiang has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Chinese Society of Radiology.
Otto Rapalino, MD (Massachusetts General Hospital) Dr. Rapalino has nothing to disclose.
Karl Gerard Helmer, PhD (Massachusetts General Hospital) The institution of Dr. Helmer has received research support from Minoryx Therapeutics. The institution of Dr. Helmer has received research support from National Institute of Health.
Daniel Balentine Mr. Balentine has nothing to disclose.
Marco Emanuele, PhD (Minoryx Therapeutics BE) Dr. Emanuele has nothing to disclose.
Laura Rodriguez-Pascau Laura Rodriguez-Pascau has received personal compensation for serving as an employee of Minoryx Therapeutics. Laura Rodriguez-Pascau has stock in Minoryx Therapeutics.
Pilar Pizcueta Pilar Pizcueta has received personal compensation for serving as an employee of Minoryx Therapeutics SL.
Guillem Pina Guillem Pina has received personal compensation for serving as an employee of Minoryx Therapeutics. Guillem Pina has stock in Minoryx Therapeutics.
Anna Vila Brau, PhD (Minoryx Therapeutics) Ms. Vila Brau has received personal compensation for serving as an employee of Minoryx Therapeutics. Ms. Vila Brau has stock in Minoryx Therapeutics.
Maria Rovira Masramon Ms. Rovira Masramon has nothing to disclose.
Adriana Mantilla, MD,PhD (Minoryx Therapeutics) Mrs. Mantilla has received personal compensation for serving as an employee of Minoryx Therapeutics.
Arun Mistry, MD (Minoryx Therapeutics) Dr. Mistry has received personal compensation for serving as an employee of Minoryx Therapeutics. Dr. Mistry has stock in Minoryx Therapeutics.
Maria Pascual, PhD (Minoryx) Dr. Pascual has received personal compensation for serving as an employee of Minoryx.
Silvia Pascual Silvia Pascual has received personal compensation for serving as an employee of Minoryx Therapeutics. Silvia Pascual has stock in Minoryx Therapeutics.
Marc Martinell Marc Martinell has received personal compensation for serving as an employee of Minoryx Therapeutics. Marc Martinell has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Minoryx Therapeutics. Marc Martinell has stock in Minoryx Therapeutics. Marc Martinell has received intellectual property interests from a discovery or technology relating to health care.
Patricia Musolino, MD, PhD 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 $5,000-$9,999 for serving as a Consultant for IONIS Pharmaceuticals . Dr. Musolino has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Vertex. The institution of Dr. Musolino has received research support from National Institute of Health-NINDS-R01. The institution of Dr. Musolino has received research support from Angea Biotherapeutics. The institution of Dr. Musolino has received research support from Minoryx Pharmaceuticals. Dr. Musolino has received publishing royalties from a publication relating to health care.