Abstract Details

Title RVT-1401, A Novel Anti-FcRn Monoclonal Antibody, Is Well Tolerated in Healthy Subjects and Reduces Plasma IgG Following Subcutaneous or Intravenous Administration

Topic Autoimmune Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-079

Objective

To characterize safety, pharmacokinetics, and pharmacodynamics of single and repeat doses of RVT-1401 administered via subcutaneous (SC) injection and intravenous (IV) infusion to healthy subjects.

Background

Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular disease thought to be directly caused by pathogenic IgG. RVT-1401 is a fully human monoclonal antibody being developed for the treatment of MG and other autoimmune disorders. RVT-1401 inhibits the binding of IgG to FcRn, resulting in rapid catabolism of IgG via lysosomal degradation.

Design/Methods Healthy subjects were enrolled in randomized single and multiple ascending dose (SAD/MAD, respectively) cohorts. Initial cohorts received open-label single 0.1 mg/kg IV (n=4) or 0.5 mg/kg SC (n=3) doses. Subsequent cohorts were randomized to receive single SC or IV doses of RVT-1401 or placebo (6:2) ranging from 100 to 765 mg. Subjects in MAD cohorts received four weekly SC doses of RVT-1401 (340 mg or 680 mg) or placebo (8:2).

Results Total IgG reduction increased with increasing doses, with a nadir at approximately 8-10 days after a single dose. An average reduction in total IgG of 47% was observed following single SC dose of 765 mg. Weekly SC injections of RVT-1401 further reduced total IgG over single dose administration, resulting in maximum reduction >75%. RVT-1401 exhibited non-linear pharmacokinetics across the dose range studied. Following SC administration of doses more than 200 mg, maximum serum concentrations were achieved within 1.5 to 4 days of administration. All adverse events (AEs) were mild to moderate in severity, with no subjects requiring premature discontinuation due to AEs.

Conclusions RVT-1401 was well tolerated following both single and multiple doses in healthy subjects. RVT-1401 rapidly reduced total IgG and is the first anti-FcRn to demonstrate a sustained IgG reduction using only SC injection. These data demonstrate the potential of RVT-1401 to treat MG and other autoimmune diseases.

Authors/Disclosures
Jon W. Collins, PharmD PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Regan Fong, PhD	No disclosure on file
Christine M. Coquery, PhD (Ionis Pharmaceuticals)	No disclosure on file
	No disclosure on file

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