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Abstract Details

Intrathecal Drug Delivery of Antisense Oligonucleotides in Huntington’s Disease: Experience of Ionis/Roche RG6042 Development Programme and Best Practice Considerations for Real-World Use
Movement Disorders
P5 - Poster Session 5 (8:00 AM-9:00 AM)
3-013
To describe the experience with intrathecal drug delivery across two clinical studies and suggest best practice for intrathecal drug administration in Huntington’s disease (HD).
Intrathecal administration involves the introduction of a drug substance into the intrathecal (subarachnoid) space of the spinal column through a spinal needle inserted typically into the lower back via lumbar puncture (LP) or via a special device (e.g. a surgically implanted catheter connected to a drug reservoir). This procedure is used when drugs cannot cross the blood–brain barrier. Once injected, drugs administered via the intrathecal route are distributed within the cerebrospinal fluid from which they can access target tissues in spinal cord and brain. The method is commonly used in spinal anaesthesia, pain management and chemotherapy; but with the advent of antisense oligonucleotides (ASOs) for treatment of neurological conditions, the indications have expanded to include spinal muscular atrophy, and, as potential new indications, amyotrophic lateral sclerosis, Alzheimer’s disease and HD.
We use the intrathecal route to deliver RG6042 (previously HTTRx), an investigational, huntingtin mRNA-targeting ASO to patients with HD. The RG6042 clinical development programme includes the double-blind, placebo-controlled, multiple ascending dose, Phase I/IIa study (NCT02519036) in 46 patients with early manifest HD and an ongoing Phase II open-label extension (NCT03342053) where patients receive 120 mg RG6042 monthly or every other month in a 62-week treatment period (total procedures ≥400 in the programme to date).
We will report on the experience with intrathecal drug delivery across these two studies and present information on suggested best practices in HD. 
Considerable experience on intrathecal administration via LP has been gained in the RG6042 clinical development programme. This experience allows us to provide a forward-looking outlook on real-world considerations of implementing intrathecally delivered therapies in the clinical interface.
Authors/Disclosures
Blair Leavitt, MD (University of British Columbia)
PRESENTER 		Dr. Leavitt has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Incisive Genetics. Dr. Leavitt has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Leavitt has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Design TX. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReMix Tx. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sintetica. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Triplet Tx. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Leavitt has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Incisive Genetics. Dr. Leavitt has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Huntington's Disease. Dr. Leavitt has stock in Incisive Genetics. Dr. Leavitt has stock in SRNAlytics. The institution of Dr. Leavitt has received research support from CIHR. The institution of Dr. Leavitt has received research support from HSC. The institution of Dr. Leavitt has received research support from Brain Canada. The institution of Dr. Leavitt has received research support from NMIN. Dr. Leavitt has received intellectual property interests from a discovery or technology relating to health care.
Edward J. Wild, MBBS, PhD, MRCP (UCL Institute of Neurology) Dr. Wild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Wild has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Skyhawk Therapeutics. Dr. Wild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ionis Pharmacauticals. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Life Sciences. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman La Roche. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vico Therapeutics. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. The institution of Dr. Wild has received research support from CHDI Foundation (non-profit).
Jee Bang, MD (Johns Hopkins University) Dr. Bang has received personal compensation in the range of $0-$499 for serving as a Consultant for GLG. Dr. Bang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Adept Field Solutions.
Anne Smith Anne Smith has received personal compensation for serving as an employee of Ionis Pharmaceuticals. Anne Smith has stock in Ionis Pharmaceuticals.
No disclosure on file
Scott Schobel Scott Schobel has received personal compensation for serving as an employee of F. Hoffman-La Roche Ltd.
Alessia Nicotra, MD, PhD, FRCP Dr. Nicotra has nothing to disclose.
Bernhard G. Landwehrmeyer, MD (Ulm University Hospital) Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ACADIA PHARMACEUTICALS INC, San Diego, CA. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck Valby, Denmark. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AOP Orphan Pharmaceuticals AG, Vienna, Austria. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Remix Therapeutics, Inc., Cambridge, MA. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for HSG Clinical Research, Inc. Dr. Landwehrmeyer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffmann-La Roche Ltd, Basel, Switzerland. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharma AG, Grenzach/Whylen, Germany. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Pharma AG, Basel, Switzerland. The institution of Dr. Landwehrmeyer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Pharma AG, Basel, Switzerland. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics, Inc., South Plainfield, NJ . Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Triplet Therapeutics, Inc. Cambridge, MA. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharma. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Pharma AG, Grenzach/Whylen, Germany. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for F. Hoffmann-La Roche Ltd, Basel, Switzerland. Dr. Landwehrmeyer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis Pharma AG, Basel, Switzerland. The institution of Dr. Landwehrmeyer has received research support from CHDI Foundation. The institution of Dr. Landwehrmeyer has received research support from European Commission. The institution of Dr. Landwehrmeyer has received research support from German Federal Government BMBF. The institution of Dr. Landwehrmeyer has received research support from German Research Council DFG. Dr. Landwehrmeyer has received publishing royalties from a publication relating to health care. Dr. Landwehrmeyer has received publishing royalties from a publication relating to health care.
Sarah J. Tabrizi, MD, PhD Sarah J. Tabrizi, MD, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for F. Hoffmann-La Roche Ltd. Sarah J. Tabrizi, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech.
Mark Guttman, MD No disclosure on file