T for 8, 12 or 16 weeks. The type and severity of adverse reactions in subjects with compensated cirrhosis (Child-Pugh A) were comparable to those seen in subjects without cirrhosis.
Adverse Reactions in HCV-Infected Adults treated with MAVYRET in Controlled Trials
ENDURANCE-2
Among 302 treatment-naïve or PRS treatment-experienced, HCV genotype 2 infected adults enrolled in ENDURANCE-2, adverse reactions (all intensity) occurring in at least 5% of subjects treated with MAVYRET for 12 weeks are presented in Table 3. In subjects treated with MAVYRET for 12 weeks, 32% reported an adverse reaction, of which 98% had adverse reactions of mild or moderate severity. No subjects treated with MAVYRET or placebo in ENDURANCE-2 permanently discontinued treatment due to an adverse drug reaction.
Table 3. Adverse Reactions Reported in ≥5% of Treatment-Naïve and PRS-Experienced Adults Without Cirrhosis Receiving MAVYRET for 12 Weeks in ENDURANCE-2
Adverse Reaction MAVYRET
12 Weeks
(N = 202)
% Placebo
12 Weeks
(N = 100)
%
Headache 9 6
Nausea 6 2
Diarrhea 5 2
ENDURANCE-3
Among 505 treatment-naïve, HCV genotype 3 infected adults without cirrhosis enrolled in ENDURANCE-3, adverse reactions (all intensity) occurring in at least 5% of subjects treated with MAVYRET for 8 or 12 weeks are presented in TABLE 4. In subjects treated with MAVYRET, 45% reported an adverse reaction, of which 99% had adverse reactions of mild or moderate severity. The proportion of subjects who permanently discontinued treatment due to adverse reactions was 0%, < 1% and 1% for the MAVYRET 8 week arm, MAVYRET 12 week arm and DCV + SOF arm, respectively.
Table 4. Adverse Reactions Reported in ≥5% of Treatment-Naïve Adults Without Cirrhosis Receiving MAVYRET for 8 Weeks or 12 Weeks in ENDURANCE-3
Adverse Reaction MAVYRET*
8 Weeks
(N = 157)
% MAVYRET
12 Weeks
(N = 233)
% DCV1 + SOF2
12 Weeks
(N = 115)
%
Headache 16 17 15
Fatigue 11 14 12
Nausea 9 12 12
Diarrhea 7 3 3
1 DCV=daclatasvir
2 SOF=sofosbuvir
* The 8 week arm was a non-randomized treatment arm.
Adverse Reactions in HCV-Infected Adults with Severe Renal Impairment Including Subjects on Dialysis
The safety of MAVYRET in subjects with chronic kidney disease (Stage 4 or Stage 5 including subjects on dialysis) with genotypes 1, 2, 3, 4, 5 or 6 chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) was assessed in 104 subjects (EXPEDITION-4) who received MAVYRET for 12 weeks. The most common adverse reactions observed in greater than or equal to 5% of subjects receiving 12 weeks of treatment with MAVYRET were pruritus (17%), fatigue (12%), nausea (9%), asthenia (7%), and headache (6%). In subjects treated with MAVYRET who reported an adverse reaction, 90% had adverse reactions of mild or moderate severity (Grade 1 or 2). The proportion of subjects who permanently discontinued treatment due to adverse reactions was 2%.
Laboratory Abnormalities
Serum bilirubin elevations
Elevations of total bilirubin at least 2 times the upper limit of normal occurred in 3.5% of subjects treated with MAVYRET versus 0% in placebo; these elevations were observed in 1.2% of subjects across the Phase 2 and 3 trials. MAVYRET inhibits OATP1B1/3 and is a weak inhibitor of UGT1A1 and may have the potential to impact bilirub |
