FDA Hepatitis Update- MAVYRET pediatric label updates

May 2, 2019

The Food and Drug Administration recently approved changes to the MAVYRET (glecaprevir and pibrentasvir) label to expand the following indications to pediatric patients 12 years and older or weighing at least 45 kg.

• HCV genotype 1, 2, 3, 4, 5, or 6 without cirrhosis or with compensated cirrhosis
• Genotype 1 population who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4 A protease inhibitor (but not both)

A summary of the major revisions are as follows:

• Section 2: DOSAGE and ADMINISTRATION

Pediatric Patients 12 years and older or weighing at least 45 kg receive the same dose as adults and is specified in subsection 2.2

Subsection 2.3 Liver or Kidney Transplant Recipients was revised to include pediatric patients 12 years and older or weighing at least 45 kg who are liver or kidney transplant recipients supported by extrapolation of efficacy in the post-transplant adult population on the basis of PK matching to pediatric transplant recipients

• Section 6 ADVERSE REACTIONS, subsection 6.1, Clinical Trials Experience was revised to include the safety data in adolescent patients based on results from the DORA-Part 1 trial as follows:

The safety of MAVYRET in HCV GT1, 2, 3, or 4 infected adolescents is based on data from a Phase 2/3 open-label trial in 47 subjects aged 12 years to less than 18 years without cirrhosis treated with MAVYRET for 8 or 16 weeks (DORA-Part 1). The adverse reactions observed were consistent with those observed in clinical studies of MAVYRET in adults. The only adverse drug reaction observed in greater than or equal to 5% of subjects receiving MAVYRET was fatigue (6%). No subjects discontinued or interrupted treatment with MAVYRET due to an adverse reaction.

• Section 8.4 Pediatric Use was revised as follows:

No dosage adjustment of MAVYRET is required in pediatric patients 12 years and older or weighing at least 45 kg.

The safety, efficacy, and pharmacokinetics of MAVYRET in HCV GT1, 2, 3, or 4 infected pediatric patients 12 years and older or weighing at least 45 kg is based on data from an open-label trial in 47 subjects without cirrhosis aged 12-18 years who were either treatment naïve (n=36) or treatment experienced (n=11) and received MAVYRET for 8 or 16 weeks (DORA-Part 1). The safety and efficacy results observed in this trial were consistent with those observed in clinical studies of MAVYRET in adults.

In pediatric patients with cirrhosis, history of a kidney and/or liver transplant, or HCV GT5 or 6 infection, the safety and efficacy of MAVYRET are supported by the comparable glecaprevir and pibrentasvir exposures observed between adolescents and adults.

The safety and effectiveness of MAVYRET in children less than 12 years of age have not been studied.

• Section 12.3 Pharmacokinetics was updated with MAVYRET drug exposure information/PK parameters in pediatric patients 12 years and older based on data from part 1 of DORA trial. In addition, revisions under the subheading Age/Gender/Race/Body Weight to include the age range of 12-88 years of age to align with the use of MAVYRET in the pediatric population

• Section 14 CLINICAL STUDIES was revised to include subsection 14.9, Clinical Trial in Pediatric Subjects (12 years to less than 18 years) and describe the clinical trial results from Part 1 of the DORA trial as follows:

The efficacy of MAVYRET was evaluated in an open-label study (DORA [Part 1]) (NCT03067129) that evaluated adolescent subjects 12 years to less than 18 years without cirrhosis who received MAVYRET for 8 or 16 weeks. Treatment duration was chosen to match approved adult durations based on HCV genotype and prior treatment experience.

47 subjects were enrolled in DORA (Part 1). The median age was 14 years (range: 12 to 17); 79% had HCV genotype 1, 6% had HCV genotype 2, 9% had HCV genotype 3, 6% had HCV genotype 4; 55% were female; 9% were Black; 77% were HCV treatment-naïve; 23% were treatment-experienced to interferon; 4% had HIV-coinfection; none had cirrhosis; the mean weight was 59 kg (range: 32 kg to 109 kg).

The overall SVR12 rate was 100% (47/47).
 

The updated label will soon be available at drugs@fda or DailyMed

 

Kimberly Struble

Division of Antiviral Products

Food and Drug Administration

 

Elizabeth Thompson

Division of Antiviral Products

Food and Drug Administration
 

Michael Stanfield Jr.

Division of Antiviral Products

Food and Drug Administration