REAL-WORLD EFFECTIVENESS IN THE LARGEST MAVYRET META-ANALYSIS2
Of 12,531 patients treated with MAVYRET (18 studies), 3657 were clearly characterized as TN, NC and treated for 8 weeks according to label (9 studies)2
99%
CURE
RATE
(n=3657, mITT SVR12)
In GT 1-4, TN, NC patients
Cure = sustained virologic response (SVR12); HCV RNA <LLOQ at 12 weeks after the end of treatment.1
METHODOLOGY2
Real-world studies reporting SVR12 in adults with HCV infection (n ≥20) treated with MAVYRET were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. The 18 identified cohorts included 7 studies from Europe (Spanish HepaC Cohort, German Hepatitis-C Registry, Italian MISTRAL, England NHS Registry, Italian NAVIGATORE-Lombardia, Scottish HCV Registry, Austrian Real-life Cohort), 6 in Japan (Japan Registry, Japan Tamori, Japan Uemura, 2 Japan DAA-experienced, Japanese GT2 retreatment), 3 in the United States (VA Registry, TRIO, Kaiser Permanente), and 2 multicountry studies (Global G/P PMOS, TARGET HCV). Of the 12,531 adults with chronic HCV infection included in the 18 studies, patients who were TN, NC, and who received on-label treatment with MAVYRET for 8 weeks (n=3657), mITT; reported in 9 of the 18 studies were included meta-analysis. Random-effects meta-analysis was used to determine SVR12 rates. The mITT population included ITT population (ie, patients treated with MAVYRET who had SVR12 data available, discontinued early, or were lost to follow-up) and excluded those with nonvirologic failure.
LIMITATIONS2
These real-world studies are retrospective, are observational in nature, and are not in the MAVYRET Prescribing Information. Results of these cohorts may differ from those observed in clinical practice, and the included studies may have differed in regard to their study design and patient characteristics. The level of detail reported across the individual studies was inconsistent, particularly with mITT reporting of SVR12 rates. There were insufficient data available to analyze SVR12 rates in patients with HCV GT 5 or GT 6 infection. The reporting of safety information in this analysis varied widely by study design and data availability. Please refer to MAVYRET’s full Prescribing Information for clinical study safety.
HIGH CURE RATES ACROSS A WIDE RANGE OF PATIENTS1,3
PPI Use Post Hoc Analysis of Clinical Trials
HIGH CURE RATES IN PATIENTS TAKING PPIs3
In Patients Taking Proton Pump Inhibitors (PPIs)
100%
CURE RATE (n=136/136 mITT SVR12)
Based on an integrated pooled analysis of GT 1-6, TN NC and CC adult patients treated for 8 weeks across 8 clinical trials.3
When coadministered with omeprazole1:
No clinically significant interactions observed
No dose adjustments required
No restrictions on timing of administration in label
The MAVYRET Prescribing Information does not include data on drug interactions or dose adjustments for PPIs other than omeprazole.1*
*MAVYRET pharmacokinetic studies were performed with 20 mg and 40 mg omeprazole once daily.
See clinical trial study designs below.
Nearly 1/3 of diagnosed HCV patients aged ≥12 years have been prescribed a PPI.4Some may also be using OTC formulations.
METHODOLOGY4
Data from TriNetX Dataworks—a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information)—including approximately 57.7 million de-identified patients in 45 large US healthcare organizations, were queried. The estimated number of individuals age 12 years or older with chronic HCV diagnosis (B18.2; n=118,949) with a prescription for omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, or rabeprazole occurring during or after HCV diagnosis in the 3 years prior to 12/17/2020 were counted (n=34,989) and the rate was calculated.
CLINICAL TRIAL STUDY DESIGNS
Integrated, pooled analysis of GT 1-6, TN adult subjects from 8 phase 2/3, open-label clinical trials. The primary endpoint of each study was SVR12.3
ENDURANCE-11,5
GT 1, TN or PRS-TE, NC subjects (± HIV-1 coinfection) were randomized to receive MAVYRET for 8 (n=351) or 12 (n=352) weeks.
ENDURANCE-31,5
GT 3, TN, NC subjects were randomized (2:1) to receive MAVYRET (n=233) or SOF + DCV (n=115) for 12 weeks; additional subjects (n=157) were subsequently enrolled and nonrandomly assigned to receive MAVYRET for 8 weeks.
ENDURANCE-5,61,6
GT 5-6, TN or PRS-TE, NC or CC subjects (n=84) received MAVYRET for 8 (n=75) or 12 (n=9) weeks.
EXPEDITION-21,7
GT 1-6, TN or PRS-TE, NC or CC subjects with HIV-1 and ART naïve or on a stable ART regimen received MAVYRET for 8 (n=137) or 12 (n=16) weeks. Treatment-experienced GT 3–infected subjects were excluded.
EXPEDITION-58
GT 1-6, TN or PRS-TE, NC or CC subjects with CKD stage 3b, 4, or 5 received MAVYRET for 8 (n=84), 12 (n=13), or 16 (n=4) weeks.
EXPEDITION-81,9
GT 1-6, TN, CC subjects (n=343) received MAVYRET for 8 weeks.
SURVEYOR-1, PART 2 (PHASE 2)10,11
GT 1, 4-6, TN or PRS-TE, NC or CC subjects received MAVYRET for 8 (n=117) or 12 (n=332) weeks.
SURVEYOR-2, PARTS 2 AND 4 (PHASE 2)1,12-14
GT 2-6, TN or PRS-TE, NC or CC subjects were randomized to receive MAVYRET for 8 (n=286), 12 (n=48), or 16 (n=4) weeks.
Compensated Cirrhotics Clinical Trial
HIGH CURE RATES IN COMPENSATED CIRRHOTICS1,9
98%
CURE RATE (n=335/343, ITT SVR12)
In GT 1-6 TN CC adult patients treated for 8 weeks in the EXPEDITION-8 clinical trial.
0% on-treatment virologic failure(n=0/343)
0.3% relapse(n=1/336)
The adverse reactions observed in CC patients were generally consistent with those observed in NC patients
The adverse reactions reported in ≥5% of CC subjects (n=343) were fatigue (8%), pruritus (7%), and headache (6%)
Most adverse events were mild in severity
No subjects discontinued due to an adverse reaction
Baseline characteristics (n=343)
27.2 median body mass index (kg/m2)
20.2 median FibroScan® score (kPa) (n=295)
18% platelets <100x109 cells/L
27% injection drug use
67% GT 1
83% white
Treatment-Naïve, Compensated Cirrhotic 8-Week Efficacy Per Protocol Results1,7
MAVYRET for 8 weeks in GT 1-6 in treatment-naïve patients with compensated cirrhosis.
PP: Per protocol excludes subjects from the ITT population with virologic breakthrough or discontinuation prior to week 8, and those missing data in the SVR12 window.
The efficacy of MAVYRET in subjects with GT 3b infection was evaluated in 2 trials conducted in China, Singapore, and South Korea. Across both trials. Subjects with GT 3b infection has a numerically lower SVR12 rate. GT 3b is uncommon in the US (<1% of HCV GT 3 infections).
Compensated cirrhosis was defined by one of the following methods:
Liver biopsy with METAVIR fibrosis score of 4 (or equivalent), FibroScan® ≥ 14.6 kPa, or FibroTest™ ≥ 0.75 and APRI > 2 at screening.
FibroScan® is a registered trademark of Echosens™ North America.
FibroTest™ is a trademark of BioPredictive S.A.S.
EXPEDITION-8 STUDY DESIGN
Single-arm, open-label, phase 3b study in GT 1-6 TN adult subjects (n=343) with compensated cirrhosis (Child-Pugh A) who received MAVYRET for 8 weeks.
Substance Use Post Hoc Analyses of Clinical Trials and Real-World Data
HIGH CURE RATES IN PATIENTS WITH SUBSTANCE USE1,15
PEOPLE WHO INJECT DRUGS (PWID)
98%
CURE RATE (n=55/56, mITT SVR12)
89%
CURE RATE (n=55/62, ITT SVR12)
2% virologic failure rate (n=1/62)1,15
62 subjects identified as current/recent PWID among 4655 chronic HCV GT 1-6 adolescents and adults who received MAVYRET for 8, 12, or 16 weeks in phase 2 and phase 3 trials1,15†
Most common adverse reactions ≥5% were fatigue (16%), headache (13%), diarrhea (6%), and nausea (6%)1
2% (n=1/62) treatment discontinuation rate due to serious adverse reactions and/or adverse reactions1
†Current/recent PWID defined as self-reported injection drug use within the last 12 months prior to starting MAVYRET.
~70% of new HCV cases occurred in people who inject drugs16
STUDY DESIGNS1
Among 4655 chronic HCV GT 1-6–infected adolescents and adults in phase 2 and 3 trials who received MAVYRET 8, 12, or 16 weeks and specified whether or not they had a history of injection-drug use, 1373 subjects were identified as PWID based on self-reported history of injection-drug use at trial enrollment. Of the PWID population, 62 subjects were considered current/recent PWID (defined as self-reported injection-drug use within the last 12 months prior to starting MAVYRET), 959 subjects were considered former PWID (defined as self-reported injection-drug use more than 12 months prior to starting MAVYRET), and 352 subjects did not specify current/recent PWID versus former PWID and were not included in the analysis.
HIGH CURE RATES IN PATIENTS WITH SUBSTANCE USE1,15
MEDICATION-ASSISTED TREATMENT (MAT)
99%
CURE RATE (n=215/216, mITT SVR12)
96%
CURE RATE (n=215/225, ITT SVR12)
0.4% virologic failure rate (n=1/225)1,15
225 subjects reported concomitant use of MAT for opioid use disorder among 4655 chronic HCV GT 1-6 adolescents and adults in subjects who received MAVYRET for 8, 12, or 16 weeks in phase 2 and 3 trials1,15
No buprenorphine/naloxone or methadone dosage adjustment is required when used concomitantly with MAVYRET. There is insufficient information to make a recommendation regarding concomitant use with naltrexone1
Most common adverse reactions ≥5% were headache (15%), fatigue (12%), nausea (11%), and diarrhea (6%)1
No treatment discontinuations due to adverse reactions were observed1
~70% of new HCV cases occurred in people who inject drugs16
STUDY DESIGNS1
Among 4655 chronic HCV GT 1-6–infected adolescents and adults in phase 2 and 3 trials who received MAVYRET and specified whether or not they had a history of injection-drug use, 225 subjects reported concomitant use of MAT for opioid use disorder and 4098 subjects reported no use of MAT (332 subjects were not included in the analysis due to missing assessment of MAT).
HIGH CURE RATES IN PATIENTS WITH SUBSTANCE USE3
ALCOHOL USE
99%
CURE RATE (n=409/412, mITT SVR12)‡
Based on an integrated pooled analysis of GT 1-6, TN NC and CC adult patients treated for 8 weeks across 8 clinical trials3
AASLD/IDSA guidelines recommend abstinence from alcohol and, when appropriate, interventions to facilitate cessation of alcohol consumption should be advised for all persons with HCV infection.17
‡Alcohol use was self-reported at the time of screening. Patients were categorized as drinker, ex-drinker, or nondrinker. Recent (within 6 months prior to study drug administration) history of alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator was excluded.3
CLINICAL TRIAL STUDY DESIGNS
Integrated, pooled analysis of GT 1-6, TN adult subjects from 8 phase 2/3, open-label clinical trials. The primary endpoint of each study was SVR12.3
ENDURANCE-11,5
GT 1, TN or PRS-TE, NC subjects (± HIV-1 coinfection) were randomized to receive MAVYRET for 8 (n=351) or 12 (n=352) weeks.
ENDURANCE-31,5
GT 3, TN, NC subjects were randomized (2:1) to receive MAVYRET (n=233) or SOF + DCV (n=115) for 12 weeks; additional subjects (n=157) were subsequently enrolled and nonrandomly assigned to receive MAVYRET for 8 weeks.
ENDURANCE-5,61,6
GT 5-6, TN or PRS-TE, NC or CC subjects (n=84) received MAVYRET for 8 (n=75) or 12 (n=9) weeks.
EXPEDITION-21,7
GT 1-6, TN or PRS-TE, NC or CC subjects with HIV-1 and ART naïve or on a stable ART regimen received MAVYRET for 8 (n=137) or 12 (n=16) weeks. Treatment-experienced GT 3–infected subjects were excluded.
EXPEDITION-58
GT 1-6, TN or PRS-TE, NC or CC subjects with CKD stage 3b, 4, or 5 received MAVYRET for 8 (n=84), 12 (n=13), or 16 (n=4) weeks.
EXPEDITION-81,9
GT 1-6, TN, CC subjects (n=343) received MAVYRET for 8 weeks.
SURVEYOR-1, PART 2 (PHASE 2)10,11
GT 1, 4-6, TN or PRS-TE, NC or CC subjects received MAVYRET for 8 (n=117) or 12 (n=332) weeks.
SURVEYOR-2, PARTS 2 AND 4 (PHASE 2)1,12-14
GT 2-6, TN or PRS-TE, NC or CC subjects were randomized to receive MAVYRET for 8 (n=286), 12 (n=48), or 16 (n=4) weeks.
REAL-WORLD EFFECTIVENESS IN PATIENTS WITH
SUBSTANCE USE OR PSYCHIATRIC DISORDERS18
Real-world data pooled from 9 studies with adult patients taking 8, 12, or 16 weeks of MAVYRET
The MAVYRET Prescribing Information does not contain efficacy, safety, or drug interaction information when MAVYRET is coadministered with specific illicit drugs. Potential drug-drug interactions with these illicit drugs have not been studied.
People who use drugs (PWUD) were defined as any patient who self-reported illicit drug use, including heroin, cocaine, marijuana, hashish, or opioids. Alcohol users were defined as those who consumed more than 2 alcoholic drinks/day. Patients with psychiatric disorders were defined as those with a history of depression or bipolar disease, depression and suicide/self-injury, and anxiety.18
METHODOLOGY18
Interim analysis of data pooled from AbbVie-sponsored postmarketing observational studies across 9 countries from November 13, 2017, to January 31, 2020. Patients were ≥18 years old with HCV GT 1-6 infection and received MAVYRET at the treating physician’s discretion according to local label, national or international recommendations, and/or local clinical practice. Patients were treatment-naïve or had been previously treated with interferon, ribavirin, sofosbuvir, or DAA; the patient population included those without cirrhosis or with compensated cirrhosis. Effectiveness was assessed through the percentage of patients who achieved SVR12 in the core population with sufficient follow-up (CPSFU). The CPSFU (n=1684) was defined as the total population (n=2036) excluding DAA-experienced patients, and those lost to follow-up, with the premature discontinuation or missing SVR12 data due to ongoing data collection.
LIMITATIONS18
These real-world studies are retrospective, are observational in nature, and may differ from Prescribing Information. Results of these cohorts may differ from those observed in clinical practice and may have differed from MAVYRET clinical trials in regard to their study design, patient characteristics, and definitions of PWUD, alcohol use, or psychiatric disorders. The reporting of safety information in this analysis varied widely by study design and data availability. Please refer to MAVYRET’s full Prescribing Information for clinical study safety.
SELECT PATIENT CHARACTERISTICS AT BASELINE18
83.5% (1701/2036) received MAVYRET for 8 weeks
9.8% (200/2036) had psychiatric disorders
22.5% (451/2036) had a history of heroin use
18.5% (322/2036) had a history of alcohol use
7.9% (158/2036) had a history of cocaine use
3.8% (77/2036) had a history of marijuana use
2.9% (58/2036) had a history of hashish use
1.3% (27/2036) had a history of opioid use
35% of patients (697/2008) reported recreational drug use§
11% (219/1990) were on stable opioid substitution therapy§
§Percentages calculated from non-missing values.
History of Depression/Bipolar Disorder Post Hoc Analysis of Clinical Trials
HIGH CURE RATES IN PATIENTS WITH A HISTORY OF DEPRESSION OR BIPOLAR DISORDER3
100%
CURE RATE (n=212/212, mITT SVR12)
Based on an integrated pooled analysis of GT 1-6, TN NC and CC adult patients treated for 8 weeks across 8 clinical trials.
CLINICAL TRIAL STUDY DESIGNS
Integrated, pooled analysis of GT 1-6, TN adult subjects from 8 phase 2/3, open-label clinical trials. The primary endpoint of each study was SVR12.3
ENDURANCE-11,5
GT 1, TN or PRS-TE, NC subjects (± HIV-1 coinfection) were randomized to receive MAVYRET for 8 (n=351) or 12 (n=352) weeks.
ENDURANCE-31,5
GT 3, TN, NC subjects were randomized (2:1) to receive MAVYRET (n=233) or SOF + DCV (n=115) for 12 weeks; additional subjects (n=157) were subsequently enrolled and nonrandomly assigned to receive MAVYRET for 8 weeks.
ENDURANCE-5,61,6
GT 5-6, TN or PRS-TE, NC or CC subjects (n=84) received MAVYRET for 8 (n=75) or 12 (n=9) weeks.
EXPEDITION-21,7
GT 1-6, TN or PRS-TE, NC or CC subjects with HIV-1 and ART naïve or on a stable ART regimen received MAVYRET for 8 (n=137) or 12 (n=16) weeks. Treatment-experienced GT 3–infected subjects were excluded.
EXPEDITION-58
GT 1-6, TN or PRS-TE, NC or CC subjects with CKD stage 3b, 4, or 5 received MAVYRET for 8 (n=84), 12 (n=13), or 16 (n=4) weeks.
EXPEDITION-81,9
GT 1-6, TN, CC subjects (n=343) received MAVYRET for 8 weeks.
SURVEYOR-1, PART 2 (PHASE 2)10,11
GT 1, 4-6, TN or PRS-TE, NC or CC subjects received MAVYRET for 8 (n=117) or 12 (n=332) weeks.
SURVEYOR-2, PARTS 2 AND 4 (PHASE 2)1,12-14
GT 2-6, TN or PRS-TE, NC or CC subjects were randomized to receive MAVYRET for 8 (n=286), 12 (n=48), or 16 (n=4) weeks.
HIV Coinfected Post Hoc Analysis of Clinical Trials
HIGH CURE RATES IN HIV-COINFECTED PATIENTS3
100%
CURE RATE (n=120/120, mITT SVR12)
Based on an integrated pooled analysis of GT 1-6, TN NC and CC adult patients treated for 8 weeks across 8 clinical trials. MAVYRET for 8 weeks was not studied in HIV-coinfected TN patients with compensated cirrhosis.1,3
MAVYRET is contraindicated with atazanavir and not recommended with darunavir, lopinavir, ritonavir, or efavirenz1
No clinically significant interactions observed with abacavir, dolutegravir, elvitegravir/cobicistat, emtricitabine, lamivudine, raltegravir, rilpivirine, tenofovir alafenamide, and tenofovir disoproxil fumarate1
The overall safety profile in HCV/HIV-1–coinfected subjects (ENDURANCE-1 and EXPEDITION-2) was similar to that observed in HCV-monoinfected subjects1
CLINICAL TRIAL STUDY DESIGNS
Integrated, pooled analysis of GT 1-6, TN adult subjects from 8 phase 2/3, open-label clinical trials. The primary endpoint of each study was SVR12.3
ENDURANCE-11,5
GT 1, TN or PRS-TE, NC subjects (± HIV-1 coinfection) were randomized to receive MAVYRET for 8 (n=351) or 12 (n=352) weeks.
ENDURANCE-31,5
GT 3, TN, NC subjects were randomized (2:1) to receive MAVYRET (n=233) or SOF + DCV (n=115) for 12 weeks; additional subjects (n=157) were subsequently enrolled and nonrandomly assigned to receive MAVYRET for 8 weeks.
ENDURANCE-5,61,6
GT 5-6, TN or PRS-TE, NC or CC subjects (n=84) received MAVYRET for 8 (n=75) or 12 (n=9) weeks.
EXPEDITION-21,7
GT 1-6, TN or PRS-TE, NC or CC subjects with HIV-1 and ART naïve or on a stable ART regimen received MAVYRET for 8 (n=137) or 12 (n=16) weeks. Treatment-experienced GT 3–infected subjects were excluded.
EXPEDITION-58
GT 1-6, TN or PRS-TE, NC or CC subjects with CKD stage 3b, 4, or 5 received MAVYRET for 8 (n=84), 12 (n=13), or 16 (n=4) weeks.
EXPEDITION-81,9
GT 1-6, TN, CC subjects (n=343) received MAVYRET for 8 weeks.
SURVEYOR-1, PART 2 (PHASE 2)10,11
GT 1, 4-6, TN or PRS-TE, NC or CC subjects received MAVYRET for 8 (n=117) or 12 (n=332) weeks.
SURVEYOR-2, PARTS 2 AND 4 (PHASE 2)1,12-14
GT 2-6, TN or PRS-TE, NC or CC subjects were randomized to receive MAVYRET for 8 (n=286), 12 (n=48), or 16 (n=4) weeks.
Severe Renal Impairment Clinical Trial
HIGH CURE RATES IN PATIENTS WITH SEVERE RENAL IMPAIRMENT1,3
100%
CURE RATE (n=65/65, mITT SVR12)3
Based on an integrated pooled analysis of GT 1-6, TN NC and CC adult patients treated for 8 weeks across 8 clinical trials. MAVYRET for 8 weeks was not studied in patients with severe renal impairment with CC.1,3
Per Prescribing Information1:
No dose adjustment is required in patients with mild, moderate, or severe renal impairment, including those on dialysis
Most common adverse reactions ≥5% in HCV-infected adults with severe renal impairment receiving 12 weeks of MAVYRET were pruritus (17%), fatigue (12%), nausea (9%), asthenia (7%), and headache (6%)
2% discontinuation rate due to adverse reactions
CLINICAL TRIAL STUDY DESIGNS
Integrated, pooled analysis of GT 1-6, TN adult subjects from 8 phase 2/3, open-label clinical trials. The primary endpoint of each study was SVR12.3
ENDURANCE-11,5
GT 1, TN or PRS-TE, NC subjects (± HIV-1 coinfection) were randomized to receive MAVYRET for 8 (n=351) or 12 (n=352) weeks.
ENDURANCE-31,5 GT 3, TN, NC subjects were randomized (2:1) to receive MAVYRET (n=233) or SOF + DCV (n=115) for 12 weeks; additional subjects (n=157) were subsequently enrolled and nonrandomly assigned to receive MAVYRET for 8 weeks.
ENDURANCE-5,61,6 GT 5-6, TN or PRS-TE, NC or CC subjects (n=84) received MAVYRET for 8 (n=75) or 12 (n=9) weeks.
EXPEDITION-21,7
GT 1-6, TN or PRS-TE, NC or CC subjects with HIV-1 and ART naïve or on a stable ART regimen received MAVYRET for 8 (n=137) or 12 (n=16) weeks. Treatment-experienced GT 3–infected subjects were excluded.
EXPEDITION-58
GT 1-6, TN or PRS-TE, NC or CC subjects with CKD stage 3b, 4, or 5 received MAVYRET for 8 (n=84), 12 (n=13), or 16 (n=4) weeks.
EXPEDITION-81,9
GT 1-6, TN, CC subjects (n=343) received MAVYRET for 8 weeks.
SURVEYOR-1, PART 2 (PHASE 2)10,11
GT 1, 4-6, TN or PRS-TE, NC or CC subjects received MAVYRET for 8 (n=117) or 12 (n=332) weeks.
SURVEYOR-2, PARTS 2 AND 4 (PHASE 2)1,12-14
GT 2-6, TN or PRS-TE, NC or CC subjects were randomized to receive MAVYRET for 8 (n=286), 12 (n=48), or 16 (n=4) weeks.
Kidney/Liver Transplant Clinical Trial
HIGH CURE RATES IN KIDNEY OR LIVER TRANSPLANT PATIENTS WITHOUT CIRRHOSIS1,19
98%
12-WEEK
CURE RATE1,19 (n=98/100, ITT SVR12)
In GT 1-4, 6 TN and GT 1, 2, 4, 6 PRS-TE, NC adult liver (n=80) or kidney (n=20) transplant recipients treated for 12 weeks in the MAGELLAN-2 clinical trial.1,19
0 on-treatment virologic failures (n=0/100)19
1 relapse (n=1/100)19
The overall safety profile in transplant recipients was similar to that observed in subjects in phase 2 and 3 studies, without a history of transplantation1
Most common adverse reactions ≥5% were headache (17%), fatigue (16%), nausea (8%), and pruritus (7%)1
No observed clinically significant interaction with tacrolimus1
MAVYRET is not recommended for use in patients requiring stable cyclosporine doses >100 mg per day1
2% of subjects experienced a serious adverse reaction, and no subjects permanently discontinued treatment due to adverse reactions1
CLINICAL TRIAL STUDY DESIGN1,19
A phase 3, single-arm, open-label study: in adult patients (n=100) with liver or kidney transplant who were TN (HCV GT 1-6) or PRS-TE (HCV GT 1, 2, 4, 6) without cirrhosis were eligible to enroll. PRS-TE, GT 3–infected patients were excluded. Patients received MAVYRET for 12 weeks. Patients had to have received a deceased or living donor liver or kidney transplant ≥3 months prior to screening and been maintained on a stable immunosuppression regimen and/or low-dose steroids.
Immunosuppressants allowed for coadministration were cyclosporine ≤100 mg, tacrolimus, sirolimus, everolimus, azathioprine, mycophenolic acid, prednisone, and prednisolone.
In GT 1-4, TN/TE||, NC patients treated with MAVYRET tablets for 8 or 16 weeks (n=47, ITT); 79% had GT 1, and 77% were HCV TN.
0% virologic failures (n=0/47)1,20
0
PATIENTS DISCONTINUED DUE TO AN ADVERSE REACTION
The only adverse reaction observed in ≥5% of subjects was fatigue (6%)
No subjects discontinued or interrupted treatment with MAVYRET due to an adverse reaction
||Treatment experienced to interferon and ribavirin.
CLINICAL TRIAL STUDY DESIGNS1,20,21
Nonrandomized, open-label phase 2/3 study (DORA) in subjects with chronic HCV aged 3 to <12 years (Part 2) and 12 to <18 years (Part 1); those with GT 1-6 (TN or PRS-TE, NC or CC, ± HIV-1) were eligible to enroll. Subjects in Part 1 (n=47) received the adult dose (300 mg glecaprevir/120 mg pibrentasvir) of MAVYRET tablets and in Part 2 (n=80) received weight-based dosing of MAVYRET oral pellets taken once daily with food for 8, 12, or 16 weeks. Treatment duration was chosen to match approved adult durations based on HCV GT and prior treatment experience. The primary efficacy endpoint was SVR12.
EFFICACY AND SAFETY IN CHILDREN ≥3 YEARS1,20,21
In children aged 3 to <12 years1,21
98%
CURE RATE (n=61/62, ITT SVR12)¶
In GT 1-4, TN/TE#, NC patients treated with MAVYRET weight-based oral pellets in packets for 8 or 16 weeks (n=80, ITT); 73% had GT 1, and 97.5% were HCV TN.
0% virologic failures (n=0/62)
1
PATIENT DISCONTINUED DUE TO AN ADVERSE REACTION
1 subject discontinued due to an adverse reaction of erythematous rash (Grade 3)
The most common adverse reactions ≥5% were vomiting, fatigue, and headache (8% each)
¶18 patients received doses lower than the recommended weight-based dosage and were not included in the efficacy analysis. Please see Full Instructions for Use for oral pellet administration information.
#Treatment experienced to interferon ribavirin.
CLINICAL TRIAL STUDY DESIGNS1,20,21
Nonrandomized, open-label phase 2/3 study (DORA) in subjects with chronic HCV aged 3 to <12 years (Part 2) and 12 to <18 years (Part 1); those with GT 1-6 (TN or PRS-TE, NC or CC, ± HIV-1) were eligible to enroll. Subjects in Part 1 (n=47) received the adult dose (300 mg glecaprevir/120 mg pibrentasvir) of MAVYRET tablets and in Part 2 (n=80) received weight-based dosing of MAVYRET oral pellets taken once daily with food for 8, 12, or 16 weeks. Treatment duration was chosen to match approved adult durations based on HCV GT and prior treatment experience. The primary efficacy endpoint was SVR12.
HIGH CURE RATES IN 8 WEEKS FOR ALL
GENOTYPES1,3
The efficacy of MAVYRET in adult subjects with GT 3b infection was evaluated in 2 trials conducted in China, Singapore, and South Korea. Across both trials, subjects with GT 3b infection had a numerically lower SVR12 rate. GT 3b is uncommon in the US (<1% of HCV GT 3 infections).1
CLINICAL TRIAL STUDY DESIGNS
Integrated, pooled analysis of GT 1-6, TN adult subjects from 8 phase 2/3, open-label clinical trials. The primary endpoint of each study was SVR12.3
ENDURANCE-11,5
GT 1, TN or PRS-TE, NC subjects (± HIV-1 coinfection) were randomized to receive MAVYRET for 8 (n=351) or 12 (n=352) weeks.
ENDURANCE-31,5
GT 3, TN, NC subjects were randomized (2:1) to receive MAVYRET (n=233) or SOF + DCV (n=115) for 12 weeks; additional subjects (n=157) were subsequently enrolled and nonrandomly assigned to receive MAVYRET for 8 weeks.
ENDURANCE-5,61,6
GT 5-6, TN or PRS-TE, NC or CC subjects (n=84) received MAVYRET for 8 (n=75) or 12 (n=9) weeks.
EXPEDITION-21,7
GT 1-6, TN or PRS-TE, NC or CC subjects with HIV-1 and ART naïve or on a stable ART regimen received MAVYRET for 8 (n=137) or 12 (n=16) weeks. Treatment-experienced GT 3–infected subjects were excluded.
EXPEDITION-58
GT 1-6, TN or PRS-TE, NC or CC subjects with CKD stage 3b, 4, or 5 received MAVYRET for 8 (n=84), 12 (n=13), or 16 (n=4) weeks.
EXPEDITION-81,9
GT 1-6, TN, CC subjects (n=343) received MAVYRET for 8 weeks.
SURVEYOR-1, PART 2 (PHASE 2)10,11
GT 1, 4-6, TN or PRS-TE, NC or CC subjects received MAVYRET for 8 (n=117) or 12 (n=332) weeks.
SURVEYOR-2, PARTS 2 AND 4 (PHASE 2)1, 12-14
GT 2-6, TN or PRS-TE, NC or CC subjects were randomized to receive MAVYRET for 8 (n=286), 12 (n=48), or 16 (n=4) weeks.
MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
CONTRAINDICATIONS
MAVYRET is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation.
MAVYRET is contraindicated with atazanavir or rifampin.
WARNINGS AND PRECAUTIONS
Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease
Postmarketing cases of hepatic decompensation/failure, some fatal, have been reported in patients treated with HCV NS3/4A protease inhibitor–containing regimens, including MAVYRET. The median time to onset for MAVYRET was 27 days. The majority had moderate or severe hepatic impairment prior to initiating therapy, including some with compensated cirrhosis at baseline but with a prior decompensation event. Rare cases were reported in patients without cirrhosis or with compensated cirrhosis; many of these patients had evidence of portal hypertension. In patients with compensated cirrhosis or evidence of advanced liver disease, perform hepatic laboratory testing as clinically indicated; and monitor for signs and symptoms of hepatic decompensation, such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage. Discontinue MAVYRET in patients who develop evidence of hepatic decompensation/failure.
Risk of Reduced Therapeutic Effect Due to Concomitant Use of MAVYRET with Certain Drugs
Carbamazepine, efavirenz, and St. John’s Wort may significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect of MAVYRET. The use of these agents with MAVYRET is not recommended.
ADVERSE REACTIONS
Most common adverse reactions observed with MAVYRET:
>10% of subjects: headache and fatigue
MAVYRET oral pellets are dispensed in unit-dose packets. Each packet contains 50 mg glecaprevir/20 mg pibrentasvir.
AASLD = American Association for the Study of Liver Diseases ALT = alanine aminotransferase APRI = aspartate aminotransferase (AST) to platelet ratio index ART = antiretroviral therapy CC = compensated cirrhotic CDC = Centers for Disease Control and Prevention CKD = chronic kidney disease CPSFU = core population with sufficient follow-up Cure = sustained virologic response (SVR12); HCV RNA <LLOQ at 12 weeks after the end of treatment DAA = direct-acting antiviral DCV = daclatasvir EC50 = 50% effective concentration GT = genotype HBV = hepatitis B virus HCV = hepatitis C virus HMG-CoA = hydroxymethylglutaryl coenzyme A IDSA = Infectious Diseases Society of America ITT = intent to treat LLOQ = lower limit of quantification MAT = medication-assisted treatment mITT = modified intent to treat NC = non-cirrhotic NS = nonstructural protein OTC = over the counter PI = protease inhibitor PPI = proton pump inhibitor PrEP = pre-exposure prophylaxis PRS-TE = prior treatment experience with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an NS5A inhibitor or HCV NS3/4A protease inhibitor PWID = people who inject drugs RBV = ribavirin Relapse = HCV RNA ≥LLOQ after end-of-treatment response among subjects who completed treatment RT-PCR = reverse transcription polymerase chain reaction SOF = sofosbuvir SVR = sustained virologic response SVR12 = sustained virologic response 12 weeks after the end of treatment TE = treatment experienced TN = treatment naïve TW4 = treatment week 4
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Conversely, the presence of this link does not imply the linked site's endorsement of MAVYRET.com/hcp or AbbVie.
You are leaving the AbbVie website and connecting to a site that is not under the control of AbbVie. AbbVie is not responsible for the contents of any such site or any further links from such site. AbbVie is providing these links to you only as a convenience, and the inclusion of any link does not imply the endorsement of the linked site by AbbVie. You should also be aware that the linked site may be governed by its own set of terms and conditions and privacy policy for which AbbVie has no responsibility.
Conversely, the presence of this link does not imply the linked site's endorsement of MAVYRET.com/hcp or AbbVie.
You are leaving the AbbVie website and connecting to a site that is not under the control of AbbVie. AbbVie is not responsible for the contents of any such site or any further links from such site. AbbVie is providing these links to you only as a convenience, and the inclusion of any link does not imply the endorsement of the linked site by AbbVie. You should also be aware that the linked site may be governed by its own set of terms and conditions and privacy policy for which AbbVie has no responsibility.
Conversely, the presence of this link does not imply the linked site's endorsement of MAVYRET.com/hcp or AbbVie.
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/
INDICATION1
MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric
IMPORTANT SAFETY INFORMATION1
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/
INDICATION1
MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric
IMPORTANT SAFETY INFORMATION1
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/
INDICATION1
MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric
IMPORTANT SAFETY INFORMATION1
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/
INDICATION1
MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric
INDICATION1
MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
CONTRAINDICATIONS
MAVYRET is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation.
MAVYRET is contraindicated with atazanavir or rifampin.
WARNINGS AND PRECAUTIONS
Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease
Postmarketing cases of hepatic decompensation/failure, some fatal, have been reported in patients treated with HCV NS3/4A protease inhibitor–containing regimens, including MAVYRET. The median time to onset for MAVYRET was 27 days. The majority had moderate or severe hepatic impairment prior to initiating therapy, including some with compensated cirrhosis at baseline but with a prior decompensation event. Rare cases were reported in patients without cirrhosis or with compensated cirrhosis; many of these patients had evidence of portal hypertension. In patients with compensated cirrhosis or evidence of advanced liver disease, perform hepatic laboratory testing as clinically indicated; and monitor for signs and symptoms of hepatic decompensation, such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage. Discontinue MAVYRET in patients who develop evidence of hepatic decompensation/failure.
Risk of Reduced Therapeutic Effect Due to Concomitant Use of MAVYRET with Certain Drugs
Carbamazepine, efavirenz, and St. John’s Wort may significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect of MAVYRET. The use of these agents with MAVYRET is not recommended.
ADVERSE REACTIONS
Most common adverse reactions observed with MAVYRET:
>10% of subjects: headache and fatigue
MAVYRET oral pellets are dispensed in unit-dose packets. Each packet contains 50 mg glecaprevir/20 mg pibrentasvir.
