Ledipasvir

Ledipasvir
Clinical data
Trade names	Harvoni (combination with sofosbuvir)
Other names	GS-5885
License data	EU EMA: by INN;
Routes of; administration	By mouth
ATC code	J05AP51 (WHO) (combination with sofosbuvir);
Legal status
Legal status	US: ℞-only;
Pharmacokinetic data
Bioavailability	76%
Protein binding	>99%
Metabolism	No cytochrome metabolism
Elimination half-life	47 hrs
Identifiers
	IUPAC name Methyl N-[(2S)-1-[(6S)-6-[5-[9,9-Difluoro-7-[2-[(1S,2S,4R)-3-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-3-azabicyclo[2.2.1]heptan-2-yl]-3H-benzimidazol-5-yl]fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]heptan-5-yl]-3-methyl-1-oxobutan-2-yl]carbamate;
CAS Number	1256388-51-8;
PubChem CID	67505836;
DrugBank	DB09027;
ChemSpider	29271894;
UNII	013TE6E4WV;
KEGG	D10442 ;
ChEBI	CHEBI:85089 ;
CompTox Dashboard (EPA)	DTXSID90154829 ;
Chemical and physical data
Formula	C49H54F2N8O6
Molar mass	889.018 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC(=O)N[C@H](C(=O)N1CC2(CC2)C[C@H]1c1ncc(-c2ccc3c(c2)C(F)(F)c2cc(-c4ccc5nc([C@@H]6[C@H]7CC[C@H](C7)N6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c5c4)ccc2-3)[nH]1)C(C)C;
	InChI InChI=1S/C49H54F2N8O6/c1-24(2)39(56-46(62)64-5)44(60)58-23-48(15-16-48)21-38(58)42-52-22-37(55-42)28-9-13-32-31-12-8-26(18-33(31)49(50,51)34(32)19-28)27-10-14-35-36(20-27)54-43(53-35)41-29-7-11-30(17-29)59(41)45(61)40(25(3)4)57-47(63)65-6/h8-10,12-14,18-20,22,24-25,29-30,38-41H,7,11,15-17,21,23H2,1-6H3,(H,52,55)(H,53,54)(H,56,62)(H,57,63)/t29-,30+,38-,39-,40-,41-/m0/s1; Key:VRTWBAAJJOHBQU-KMWAZVGDSA-N;

Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences.^[1] After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C.^[2]^[3] The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.

Ledipasvir is an inhibitor of NS5A, a hepatitis C virus protein.

Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of the nucleotide analog inhibitor sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.^[4]^[5] The sofosbuvir/ledipasvir coformulation is being tested with and without ribavirin. In February 2014 Gilead filed for United States Food and Drug Administration (FDA) approval of ledipasvir/sofosbuvir oral treatment, without interferon and ribavirin.^[6]

On 10 October 2014 the FDA approved the combination product ledipasvir/sofosbuvir called Harvoni.^[7]

^ "Ledipasvir" (PDF). United States Adopted Name. Archived from the original (PDF) on 2016-01-31. Retrieved 2013-05-14.
^ "Ledipasvir-submitted-to-FDA". Archived from the original on 2014-03-02. Retrieved 2014-04-03.
^ "GS-5885". Gilead Sciences. Archived from the original on 2013-04-10. Retrieved 2013-03-08.
^ ELECTRON: 100% Suppression of Viral Load through 4 Weeks’ Post-treatment for Sofosbuvir + Ledipasvir (GS-5885) + Ribavirin for 12 Weeks in Treatment-naïve and -experienced Hepatitis C Virus GT 1 Patients Archived 2013-03-23 at the Wayback Machine. Gane, Edward et al. 20th Conference on Retroviruses and Opportunistic Infections. March 3–6, 2013. Abstract 41LB.
^ CROI 2013: Sofosbuvir + Ledipasvir + Ribavirin Combo for HCV Produces 100% Sustained Response Archived 2015-09-24 at the Wayback Machine. Highleyman, Liz. HIVandHepatitis.com. 4 March 2013.
^ "Gilead Files for U.S. Approval of Ledipasvir/Sofosbuvir Fixed-Dose Combination Tablet for Genotype 1 Hepatitis C". Gilead Sciences. 10 February 2014. Archived from the original on 2 March 2014. Retrieved 14 March 2014.
^ "U.S. Food and Drug Administration Approves Gilead's Harvoni (Ledipasvir/Sofosbuvir), the First Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C". 10 October 2014. Archived from the original on 12 October 2018. Retrieved 10 October 2014.

[1] "Ledipasvir" (PDF). United States Adopted Name. Archived from the original (PDF) on 2016-01-31. Retrieved 2013-05-14.

[2] "Ledipasvir-submitted-to-FDA". Archived from the original on 2014-03-02. Retrieved 2014-04-03.

[3] "GS-5885". Gilead Sciences. Archived from the original on 2013-04-10. Retrieved 2013-03-08.

[4] ELECTRON: 100% Suppression of Viral Load through 4 Weeks’ Post-treatment for Sofosbuvir + Ledipasvir (GS-5885) + Ribavirin for 12 Weeks in Treatment-naïve and -experienced Hepatitis C Virus GT 1 Patients Archived 2013-03-23 at the Wayback Machine. Gane, Edward et al. 20th Conference on Retroviruses and Opportunistic Infections. March 3–6, 2013. Abstract 41LB.

[5] CROI 2013: Sofosbuvir + Ledipasvir + Ribavirin Combo for HCV Produces 100% Sustained Response Archived 2015-09-24 at the Wayback Machine. Highleyman, Liz. HIVandHepatitis.com. 4 March 2013.

[6] "Gilead Files for U.S. Approval of Ledipasvir/Sofosbuvir Fixed-Dose Combination Tablet for Genotype 1 Hepatitis C". Gilead Sciences. 10 February 2014. Archived from the original on 2 March 2014. Retrieved 14 March 2014.

[7] "U.S. Food and Drug Administration Approves Gilead's Harvoni (Ledipasvir/Sofosbuvir), the First Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C". 10 October 2014. Archived from the original on 12 October 2018. Retrieved 10 October 2014.

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