- Category: HCV Treatment
- Published on Thursday, 22 December 2016 00:00
- Written by HIVandHepatitis.com
This year saw the approval of new highly effective direct-acting antiviral therapies for hepatitis C, with more in the pipeline and due for approval in 2017.
The advent of direct-acting antivirals (DAAs) used in interferon-free regimens has made hepatitis C treatment shorter, more convenient, and much more effective, but there is still room for better options for difficult-to-treat patients, including people with prior treatment experience, liver cirrhosis, and hepatitis C virus (HCV) genotypes other than 1.
In January the U.S. Food and Drug Administration (FDA) approved Merck's Zepatier, a once-daily coformulation of the HCV protease inhibitor grazoprevir and NS5A inhibitor elbasvir, for genotypes 1 and 4. In June the agency approved Gilead Sciences' Epclusa, a once-daily combination pill containing the nucleotide HCV polymerase inhibitor sofosbuvir and NS5A inhibitor velpatasvir. AbbVie received approval of Viekira XR, a more convenient once-daily coformulation of its paritaprevir/ritonavir/ ombitasvir/dasabuvir "3D" regimen.
The C-EDGE studies showed that grazoprevir/elbasvir produced cure rates of 90% or better for previously untreated people (C-EDGE Treatment-naive), prior non-responders (C-EDGE Treatment-experienced), people with HIV/HCV coinfection (C-EDGE Co-infected), patients with advanced liver disease (C-SALT), and people who inject drugs (C-EDGE CO-STAR).
The ASTRAL trials showed that sofosbuvir/velpatasvir cured almost all patients with HCV genotypes 1, 2, 4, 5, and 6, as well as up to 94% of people with decompensated cirrhosis (with ribavirin), 95% of people with harder-to-treat genotype 3, and 95% of HIV/HCV coinfected patients.
The AASLD/IDSA hepatitis C guidelines and EASL European guidelines were updated this year to reflect the availability of new regimens. The World Health Organization also released updated guidelines emphasizing options that are broadly applicable worldwide. Pangenotypic regimens that work against all HCV genotypes have the potential to be used anywhere in the world without the need for prior genotypic testing.
In December Gilead and AbbVie both announced that they have applied for FDA approval of new ribavirin-free pangenotypic regimens.
Gilead's new once-daily triple coformulation combines sofosbuvir, velpatasvir, and the HCV protease inhibitor voxilaprevir (formerly GS-9857). The Phase 3 POLARIS trials, presented at the AASLD Liver Meeting, showed that sofosbuvir/velpatasvir/voxilaprevir for 8 weeks produced an overall cure rate of 95% for previously untreated people with all HCV genotypes, while a 12-week regimen cured up to 97% of patients previously treated with other DAAs. The 8-week regimen cured almost all of the most difficult-to-treat genotype 3 patients with liver cirrhosis.
AbbVie's once-daily "G/P" coformulation contains the HCV protease inhibitor glecaprevir (formerly ABT-493) and NS5A inhibitor pibrentasvir (formerly ABT-530). In the ENDURANCE trials glecaprevir/pibrentasvir taken for 8 or 12 weeks cured up to 99% of non-cirrhotic people with HCV genotypes 1, 2, 4, 5, and 6. In the SURVEYOR-2 study the combo taken for 12 or 16 weeks cured at least 96% of genotype 3 patients with cirrhosis, and it cured almost all patients with advanced kidney disease in the EXPEDITION-4 trial.
Merck is also testing a pangenotypic triple coformulation containing grazoprevir plus the investigational NS5B polymerase inhibitor MK-3682 and NS5A inhibitor ruzasvir (formerly MK-8408). The C-CREST and C-SURGE studies showed that this combination cured 86% to 100% of patients with HCV genotypes 1, 2, or 3, including those previously treated with other DAAs.
The high price of hepatitis C treatment continues to limit access worldwide, leading some patients to turn to low-cost generic versions of approved DAAs. An Australian study presented at the EASL International Liver Congress and international analyses presented at the International Congress on Drug Therapy in Glasgow found that generic DAAs were as safe and effective as the equivalent branded products.