M-07: Impact of Sofosbuvir/Velpatasvir/Voxilaprevir Intervention on Recent Remission Rates of Direct Acting Antivirals.
Touro College of Pharmacy United States
To evaluate the efficacy of sofosbuvir/velpatasvir/voxilaprevir, the only drug approved for retreatment of chronic hepatitis C infection, providing an alternative pangenotypic 8-week lower cost of therapy, and addressing the 10-15% incidence rates of genotype 1 resistance associated substitutions.
A literature search was conducted on PubMed for articles pertaining to SOF/VEL/VOX that included the terms “sofosbuvir”, “velpatasvir”, “voxilaprevir” and “Hepatitis C”. Articles were limited to a time frame of 2017-2018. After applying the inclusion criteria eight of the articles were included.
The literature search revealed 268 articles in total. However, eight met the inclusion criteria and were utilized in this analysis. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) was studied in hepatitis C (HCV) patients in a series of multicentral phase III clinical trials known as POLARIS. In POLARIS-1, patients who previously received an NS5A inhibitor such as ledipasvir or daclatasvir were treated with either (SOF/VEL/VOX) or placebo for 12 weeks. None of the patients receiving placebo achieved a sustained virologic response (SVR) while 96% of patients on SOF/VEL/VOX achieved SVR. POLARIS-2 studied the effectiveness of a SOF/VEL/VOX 8-week regimen versus a sofosbuvir/velpatasvir (SOF/VEL) 12-week regimen in patients with or without compensated cirrhosis except for those with genotype 3 without cirrhosis. Although the study did not show that SOF/VEL/VOX was non-inferior to SOF/VEL, 95% of patients receiving SOF/VEL/VOX achieved SVR and 98% of patients receiving SOF/VEL achieved SVR. POLARIS-3 also studied the effectiveness of SOF/VEL/VOX 8-week regimen vs SOF/VEL 12-week regimen but in the patients that were excluded in POLARIS-3 (genotype 3 without cirrhosis). Both treatment arms achieved 96% SVR. Finally, POLARIS-4 consisted of patients who have previously failed an HCV direct-acting antiviral (DAA) containing regimen without a NS5A inhibitor. These patients were randomized to either SOF/VEL/VOX or SOF/VEL for 12 weeks. For the patients receiving SOF/VEL/VOX 97% achieved SVR and only 90% of patients taking the dual therapy achieved SVR. Furthermore, with a cost of $74,760 for 12 weeks, and $49,840 for 8 weeks, SOF/VEL/VOX carries a higher economical advantage over first line treatment. There was no serious drug related adverse events in the POLARIS studies. However, common side effects included headache, fatigue, diarrhea and nausea.
With the global prominence of HCV genotypes not treated by the popularized drug sofosbuvir/ledipasvir, as well as the emergence of resistance-associated substitutions (RASs) across all genotypes that lower NS5A inhibitor treatment success, alternative therapy is vital to the treatment of HCV. Although non-inferiority wasn’t established by POLARIS-2 for SOF/VEL/VOX 8-week therapy over SOF/VEL for 12 weeks in genotype 1 patients not previously treated, the other phase III clinical studies in the series demonstrated its importance in the future treatment of HCV. POLARIS-1 determined an SVR of 96% in all HCV patients previously exposed to NS5A inhibitors, indicating its use in retreatment for patients who failed on prior therapy with or without compensated cirrhosis. It was further shown that SOF/VEL/VOX 8-week therapy and SOF/VEL 12-week therapy were comparable in patients infected with genotype 3 with compensated cirrhosis who had not been treated with DAAs in the past. These two trials alone demonstrated the success of this drug combination, however, POLARIS-4 additionally established 96-100% SVR in treatment of patients with genotypes 1-4 who had previously been treated with DAAs without a NS5A inhibitor. Collectively these trials have demonstrated SOF/VEL/VOX to be an effective alternative treatment in chronic HCV genotypes 1-6, especially in the case of development of RASs either associated with prior DAA exposure or not. Treatment comes at the cost of slightly higher rates of adverse effects such as fatigue, diarrhea, and nausea, but with the benefit of the possibility of shorter treatment durations at a lower cost. The addition of the NS3/4A inhibitor voxilaprevir has proven to be a beneficial strategy in the cure of DAA resistant HCV strains, and paves the way for future drug development to answer the threat of growing resistance.