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HCV & HCV/HIV Coinfection Micro-Elimination Grants: funding for 30+ projects -
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New label attached
The Food and Drug Administration (FDA) has approved updates to the Mavyret (glecaprevir, pibrentasvir; AbbVie) labeling to include new data from the M14-730 HCV/HIV-1 co-infection study, and from the M13-596 liver and renal transplant study.
Mavyret consists of glecaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor. It is currently indicated to treat adults with chronic HCV genotype 1, 2, 3, 4, 5, or 6 without cirrhosis or with compensated cirrhosis (Child-Pugh A). It is also indicated to treat adults with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.
The Dosage and Administration section has been revised to state that Mavyret is recommended for 12 weeks in liver or kidney transplant recipients. A 16-week treatment duration is recommended for genotype 1-infected patients who are NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor (PI) or in genotype 3-infected patients who are PRS treatment-experienced; PRS is defined as prior treatment experience with regimens containing peginterferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor.
The Adverse Reactions section was updated to include safety data for HCV/HIV-1 co-infected patients and those with liver or kidney transplant. Findings from the open-label EXPEDITION-2 (N=153) study and ENDURANCE-1 (N=33) study of HCV/HIV-1 co-infected patients showed similar safety profiles to that observed in HCV mono-infected patients. Fatigue, nausea, and headache were the most common adverse reactions seen among the Mavyret arm in EXPEDITION-2.
Safety data from the MAGELLAN-2 (N=100) study among post-liver or -kidney transplant patients with genotypes 1, 2, 3, 4, or 6 chronic HCV infection without cirrhosis showed a similar safety profile to Phase 2/3 studies of patients without a history of transplantation. Headache, fatigue, nausea, and pruritus were the most common adverse reactions seen in the Mavyret arm.
Similarly, the Clinical Studies sections were updated to include findings from the EXPEDITION-2 and MAGELLAN-2 studies. In the EXPEDITION-2 study, HCV/HIV-1 co-infected patients who were HCV treatment-naive or treatment-experienced to combinations of peginterferon, ribavirin, and/or sofosbuvir received Mavyret for 8 weeks (if no cirrhosis) or 12 weeks (if compensated cirrhosis). The SVR12 rate in the co-infected patients was 98% (N=150).
In the single-arm, open-label MAGELLAN-2 study, post-transplant patients who were HCV treatment-naive or treatment-experienced to combinations of peginterferon, ribavirin, and/or sofosbuvir received Mavyret for 12 weeks. The overall SVR12 rate in post-transplant patients was 98% (N=98).
Mavyret is available as 100mg/40mg strength tablets.
For more information call (800) 633-9110 or visit Mavyret.com.
14.7 Treatment-Naïve or PRS Treatment-Experienced Adults with HCV/HIV-1 Coinfection without Cirrhosis or with Compensated Cirrhosis
EXPEDITION-2 was an open-label study in 153 HCV/HIV-1-coinfected subjects. Subjects without cirrhosis received MAVYRET for 8 weeks and subjects with compensated cirrhosis received MAVYRET for 12 weeks. The study included subjects who were HCV treatment-naïve or treatment-experienced to combinations of (peg)interferon, ribavirin, and/or sofosbuvir, with the exception of GT3-infected subjects who were all treatment naïve.
Of the 153 subjects treated, the median age was 45 years (range: 23 to 74); 63% had HCV genotype 1, 7% had HCV genotype 2, 17% had HCV genotype 3, 11% had HCV genotype 4, 2% had HCV genotype 6; 11% had cirrhosis; 84% were male; and 16% were Black. In EXPEDITION-2, the SVR12 rate in HCV/HIV-1 co-infected subjects was 98% (150/153). One subject experienced on-treatment virologic failure and no subjects relapsed.
14.5 Treatment-Naïve and PRS Treatment-Experienced Adults with CKD Stage 4 and 5 and Chronic HCV Infection without Cirrhosis or with Compensated Cirrhosis
EXPEDITION-4 was an open-label, single-arm, multicenter trial to evaluate safety and efficacy in subjects with severe renal impairment (CKD Stages 4 and 5) with compensated liver disease (with and without Child-Pugh A cirrhosis). There were 104 subjects enrolled, 82% were on hemodialysis, and 53%, 15%, 11%, 19%, 1% and 1% were infected with HCV genotypes 1, 2, 3, 4, 5 and 6; respectively. Overall, 19% of subjects had compensated cirrhosis and 81% of subjects were non-cirrhotic; 58% and 42% of subjects were treatment-naïve and PRS treatment-experienced, respectively. The overall SVR12 rate was 98% and no subjects experienced virologic failure. The presence of renal impairment did not affect efficacy; no dose-adjustments were required during the trial.
14.8 Treatment-Naïve or PRS Treatment-Experienced Adults with Liver or Kidney Transplant without Cirrhosis
MAGELLAN-2 was a single-arm, open-label study in 100 post-liver or -kidney transplant HCV GT 1, 2, 3, 4, or 6 infected subjects without cirrhosis who received MAVYRET for 12 weeks. The study included subjects who were HCV treatment-naïve or treatment-experienced to combinations of (peg)interferon, ribavirin, and/or sofosbuvir, with the exception of GT3-infected subjects who were all treatment-naïve.
Of the 100 subjects treated, the median age was 60 years (range: 39 to 78); 57% had HCV genotype 1, 13% had HCV genotype 2, 24% had HCV genotype 3, 4% had HCV genotype 4, 2% had HCV genotype 6; 75% were male; 8% were Black; 80% of subjects were post-liver transplant and 20% were post-kidney transplant. Immunosuppressants allowed for co-administration were cyclosporine ≤100 mg, tacrolimus, sirolimus, everolimus, azathioprine, mycophenolic acid, prednisone, and prednisolone.
The overall SVR12 rate in post-transplant subjects was 98% (98/100). There was one relapse and no on-treatment virologic failures.
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