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Maviret 100mg/40mg film-coated tablets(七)
s at the time of failure.
Effect of baseline HCV amino acid polymorphisms on treatment response
A pooled analysis of treatment-naïve and pegylated interferon, ribavirin and/or sofosbuvir treatment-experienced subjects receiving Maviret in the Phase 2 and Phase 3 clinical studies was conducted to explore the association between baseline polymorphisms and treatment outcome and to describe substitutions seen upon virologic failure. Baseline polymorphisms relative to a subtype-specific reference sequence at amino acid positions 155, 156, and 168 in NS3, and 24, 28, 30, 31, 58, 92, and 93 in NS5A were eva luated at a 15% detection threshold by next-generation sequencing. Baseline polymorphisms in NS3 were detected in 1.1% (9/845), 0.8% (3/398), 1.6% (10/613), 1.2% (2/164), 41.9% (13/31), and 2.9% (1/34) of subjects with HCV genotype 1, 2, 3, 4, 5, and 6 infection, respectively. Baseline polymorphisms in NS5A were detected in 26.8% (225/841), 79.8% (331/415), 22.1% (136/615), 49.7% (80/161), 12.9% (4/31), and 54.1% (20/37) of subjects with HCV genotype 1, 2, 3, 4, 5, and 6 infection, respectively.
Genotype 1, 2, 4, 5, and 6: Baseline polymorphisms in genotypes 1, 2, 4, 5 and 6 had no impact on treatment outcome.
Genotype 3: For subjects who received the recommended regimen (n=309), baseline polymorphisms in NS5A (Y93H included) or NS3 did not have a relevant impact on treatment outcomes. All subjects (15/15) with Y93H and 75% (15/20) with A30K in NS5A at baseline achieved SVR12. The overall preva lence of A30K and Y93H at baseline was 6.5% and 4.9%, respectively. The ability to assess the impact of baseline polymorphisms in NS5A was limited among treatment-naïve subjects with cirrhosis and treatment-experienced subjects due to low preva lence of A30K (1.6%, 2/128) or Y93H (3.9%, 5/128).
Cross-resistance
In vitro data indicate that the majority of the resistance-associated substitutions in NS5A at amino acid positions 24, 28, 30, 31, 58, 92, or 93 that confer resistance to ombitasvir, daclatasvir, ledipasvir, elbasvir, or velpatasvir remained susceptible to pibrentasvir. Some combinations of NS5A substitutions at these positions showed reductions in susceptibility to pibrentasvir. Glecaprevir was fully active against resistance-associated substitutions in NS5A, while pibrentasvir was fully active against resistance-associated substitutions in NS3. Both glecaprevir and pibrentasvir were fully active against substitutions associated with resistance to NS5B nucleotide and non-nucleotide inhibitors.
Clinical efficacy and safety
Table 7 summarizes clinical studies conducted with Maviret in subjects with HCV genotype 1, 2, 3, 4, 5 or 6 infection.
Table 7: Clinical studies conducted with Maviret in subjects with HCV genotype 1, 2, 3, 4, 5 or 6 Infection
TN=treatment naïve, TE=treatment experienced (includes previous treatment that included pegIFN (or IFN), and/or RBV and/or sofosbuvir), PI=Protease Inhibitor, CKD=chronic kidney disease
a. Included 33 subjects co-infected with HIV-1.
b. GT2 from SURVEYOR-2 Parts 1 and 2 - Maviret for 8 weeks (n=54) or 12 weeks (n=25); GT2 from SURVEYOR-2 Part 4 - Maviret for 8 weeks (n=145).
c. GT3 without cirrhosis from SURVEYOR-2 Parts 1 and 2 - Maviret for 8 (n=29) or 12 weeks (n=54); GT3 without cirrhosis from SURVEYOR-2 Part 3 - Maviret for 12 weeks (n=22) or 16 weeks (n=22).
d. GT3 with cirrhosis from SURVEYOR-2 Part 2 - Maviret for 12 weeks (n=24) or 16 weeks (n=4); GT3 with cirrhosis from SURVEYOR-2 Pa |
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