Abstract Details

Title A phase I/II open-label gene replacement clinical study for late onset Pompe disease

Topic Child Neurology and Developmental Neurology

Presentation(s) Child Neurology and Developmental Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 044

Objective Pompe disease is an autosomal recessive neuromuscular disease caused by mutations in the GAA gene, which encodes the enzyme acid alpha-glucosidase (GAA). Deficiency in functional GAA leads to accumulation of glycogen within lysosomes resulting in cell and tissue damage, primarily in skeletal and cardiac muscles. Pompe disease spans a continuum of disease severity in which age of disease onset, degree of myopathy and extent of organ involvement correlate with residual enzyme activity. Late-onset Pompe disease (LOPD) is characterized by progressive skeletal myopathy with proximal muscle weakness and respiratory insufficiency. With disease progression LOPD can necessitate a full-time ventilator, and wheelchair use to maintain mobility.

Background AT845, an AAV-based gene therapy for Pompe disease currently under clinical development, is designed to target muscle tissue, the predominantly affected tissue in Pompe disease. Preclinical studies in GAAKO mice infused with AT845 have resulted in GAA activity ranging from 25% to 500% of wild-type levels in muscle at the clinical starting dose of 3x10¹³ vg/kg. Therefore, a one-time infusion of AT845 has the potential for stable, long-term sustained expression of GAA in muscle with therapeutic benefit in motor function.

Design/Methods FORTIS (NCT04174105), an ongoing Phase I/II, multicenter, open-label, ascending-dose clinical study is assessing the safety and preliminary efficacy of AT845 in up to 8 subjects ≥ 18 years of age with LOPD. Study subjects will receive a single intravenous infusion of AT845 and will be followed for one year with frequent monitoring of clinical and biochemical endpoints including GAA activity and protein level in muscle.

Results

Subjects will then be followed for 4 years to determine duration of response and long-term effects.

Conclusions An update will be provided on the design and progress of this clinical study at the 2021 Annual �鶹��ýӳ�� meeting. This abstract is also submitted to be presented at the 2021 WorldSymposium, San Diego.

Authors/Disclosures
Tahseen Mozaffar, MD, F�鶹��ýӳ�� (University of California Irvine) PRESENTER	Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Grifols. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas Gene Therapy. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from Sanofi. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Astellas Gene Therpay. The institution of Dr. Mozaffar has received research support from Cartesian. The institution of Dr. Mozaffar has received research support from Cabaletta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH.
John W. Day, MD, PhD (Stanford University School of Medicine)	Dr. Day 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 Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Cheryl Wong Po Foo (Audentes Therapeutics)	Cheryl Wong Po Foo has nothing to disclose.
Nathan Bachtell, MD (AUDENTES)	Dr. BACHTELL has received personal compensation for serving as an employee of Symic Bio. Dr. BACHTELL has received personal compensation for serving as an employee of Audentes.
	No disclosure on file