This study assessed the bioequivalence of a generic glecaprevir/pibrentasvir (G/P) formulation compared to the brand name version under fed conditions using a randomized, single-dose, crossover design. Results showed that the generic formulation is bioequivalent to the brand, with similar pharmacokinetic profiles and no adverse events reported. Additionally, recent research on a 4-week G/P regimen demonstrated high efficacy and good tolerability, further supporting the effectiveness of both the generic formulation and the shorter treatment duration for HCV.
This open-label, randomized, single-dose, 2-period, crossover clinical trial was conducted to assess the bioequivalence and pharmacokinetics of a generic G/P formulation compared to the brand name version for treatment of HCV infection under fed conditions. The results demonstrated that the generic and brand name formulations are bioequivalent, as reflected by their similar pharmacokinetic profiles. Additionally, both formulations were well tolerated, with no adverse events reported among participants.1
3 Main Takeaways
- The generic G/P formulation has been shown to be bioequivalent to the brand name version, demonstrating similar pharmacokinetic profiles and safety under fed conditions.
- A recent study highlights that a 4-week G/P regimen is effective for HCV treatment, achieving high rates of Sustained Virologic Response (SVR12) and showing good tolerability.
- The generic and brand formulations of G/P, as well as the 4-week regimen, have been well-tolerated with no serious adverse events reported.
The geometric mean ratios for maximum plasma concentration (Cmax) and the area under the concentration-time curve from drug administration to the last measurable concentration (AUC0-t) of the generic formulation relative to the brand name product fell within the bioequivalence range of 80%-125%. Both formulations exhibited similar pharmacokinetic profiles for both drugs.1
The trial included 56 healthy adult volunteers who were randomly assigned in a 1:1 ratio to receive a single dose of either the generic or brand formulation. Following a 7-day washout period, participants were given the alternate product. Blood samples were collected at specified intervals up to 48 hours after dosing. Plasma levels of G/P were measured using a validated high-performance liquid chromatography-tandem mass spectrometry method.1
A recent study has shown more positive results, with shortened treatments demonstrating promise in the early stages of HCV. The study on the 4-week G/P regimen highlights its potential as a strategy for HCV elimination, particularly among populations co-infected with HIV.2
The results showed that the 4-week G/P regimen achieved a Sustained Virologic Response at 12 weeks (SVR12) in 84% of participants, with the rate increasing to 86% when excluding one participant lost to follow-up. The SVR12 rates were 83% among those with HIV and 86% among those without HIV. No serious adverse events were associated with the treatment, indicating that the participants well tolerated it. Although, six participants experienced a recurrence of viremia by the 12-week mark, yet all four who received alternative treatments subsequently achieved SVR12.2
In 2017, the FDA approved G/P, also known as Mavyret, for the treatment of adults with chronic HCV genotypes 1-6, including those with mild cirrhosis or moderate to severe kidney disease, as well as for previously treated HCV genotype 1 patients. The approval included an 8-week treatment option, the shortest approved duration for all HCV genotypes, demonstrated high cure rates in clinical trials, although common adverse reactions included headache, fatigue, and nausea.3 These recent clinical trials of 4-week regimens represent a significant advancement in HCV treatment, showing promising progress in curing the virus.
Together, these studies confirm the therapeutic equivalence of the generic G/P formulation and support the efficacy of the 4-week regimen, emphasizing both the safety profile and effectiveness of G/P in HCV treatment.
References
Noskov S, Parulya O, Lutskova L, et al. Bioequivalence and Safety of Generic Glecaprevir/Pibrentasvir Compared to a Branded Product: A Randomized, Crossover Study in Healthy Volunteers. Clin Pharmacol Drug Dev. Published August 14, 2024. Accessed August 19, 2024. doi:10.1002/cpdd.1463
Kim A, Kang M, Umbleja T, et. al. A Phase II Trial of 4 Weeks of Glecaprevir/Pibrentasvir for Early Hepatitis C Virus: ACTG A5380. Poster #969 presented at CROI 2024. March 3-6, 2023. Denver, CO.
