Compositions and methods for treatment of hepatitis D virus infection
Described are RNA interference (RNAi) agents for treating a Hepatitis D Virus (HDV) infection in a subject in need thereof.
1 . 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.
2 . The method of claim 1 , wherein the treatment further comprises administering an effective amount of a nucleoside analog or a nucleotide analog.
3 . The method of claim 1 , wherein the human subject further comprises cirrhosis.
4 . The method of claim 1 , wherein the human subject is a patient without cirrhosis.
5 . The method of claim 2 , wherein the administration of the nucleoside analog or nucleotide analog is continued after stopping the administration of the effective amount of the RNAi component.
6 . The method of claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent, excipient, or a combination of any of the foregoing.
7 . The method of claim 1 , wherein the first and second RNAi agents in the RNAi component are administered in a ratio of about 2:1.
8 . The method of claim 1 , wherein the RNAi component is administered at about 50 mg per dose.
9 . The method of claim 1 , wherein the RNAi component is administered at about 200 mg per dose.
10 . The method of claim 6 , wherein the pharmaceutical composition is a sterile aqueous solution.
11 . The method of claim 6 , wherein the pharmaceutical composition is a sterile powder for the extemporaneous preparation of a sterile injectable solution or dispersion.