Compositions and methods for treatment of hepatitis D virus infection

A method of treating a Hepatitis D Virus infection in a human subject in need thereof, comprising administering a pharmaceutical composition comprising an RNAi component, wherein the RNAi component comprises:

• (i) a first RNAi agent comprising:
• an antisense strand comprising a modified nucleotide sequence of asGfsasAfaAfuUfgAfgAfgAfaGfuCfcasc (SEQ ID NO:2) and a sense strand comprising a modified nucleotide sequence of (NAG37)s-(invAb)sguggacuuCfUfCfucaauuuucus(invAb) (SEQ ID NO:11);
• and
• (ii) a second RNAi agent comprising:
• an antisense strand comprising a modified nucleotide sequence of usAfscsCfaAfuUfuAfuGfcCfuAfcAfgcsg (SEQ ID NO:8) and a sense strand comprising a modified nucleotide sequence of (NAG37)s-(invAb)scgcuguagGfCfAfuaaauugguas(invAb) (SEQ ID NO:16),
• wherein (NAG37) s has the structure:
• wherein (invAb) is an inverted (3′-3′ linked) abasic deoxyribonucleotide;
• wherein (invAb) s is an inverted abasic deoxyribonucleotide-5′-phosphorothioate;
• wherein a, g, c and u are 2′-O-methyl modified nucleotides;
• wherein Af, Cf, Gf, and Uf are 2′-fluoro modified nucleotides;
• wherein s is a phosphorothioate linkage;
• and
• wherein the RNAi component is administered to the human subject via intravenous or subcutaneous injection and in a dose of 40-200 mg once monthly or once every four weeks.