A combination of Bristol-Myers Squibb’s daclatasvir and Gilead Sciences’ sofosbuvir has cured 97% of hepatitis C virus (HCV) infections in patients co-infected with HIV in a phase III trial.
The once-daily regimen is big news for the sizeable community of HIV/HCV – estimated at around 7 million people worldwide – who often cannot tolerate or take standard treatments for hep C because of adverse events, including drug interactions with antiretroviral therapies used to treat HIV.
The phase III trial – called ALLY-2 – showed that the dual regimen of BMS’ NS5A inhibitor Daklinza (daclatasvir) and Gilead’s NS5B polymerase inhibitor Sovaldi (sofosbuvir) could cure almost all co-infected patients of HCV within 12 weeks.
Critically, the regimen “did not require alteration of HIV medications because of potential drug-drug interactions,” according to lead investigator David Wyles of the University of California San Diego. “This is a paramount consideration for clinicians treating this patient population,” he added.
The trial involved both treatment-naïve and treatment-experienced co-infected patients, and there were no discontinuations due to adverse events.
“In many settings, hepatitis C is now a leading cause of death among HIV co-infected patients,” according to Mark Sulkowski, of Johns Hopkins University School of Medicine.
The data could provide an important boost for BMS, whose Daklinza product has been held back by an FDA decision to deny approval because the drug it was developed alongside – NS3/4A protease inhibitor asunepravir – had been dropped from development. The ALLY-2 data could help satisfy an FDA request for more data on daclatasvir’s use in combination with other HCV therapies.
Nevertheless, combination regimens coming out of other companies’ pipelines have made significant progress in the market leaving other directly acting antivirals (DAAs) such as Daklinza at risk of being side lined. These include Gilead’s Harvoni – which adds NS5A ledipasvir to sofosbuvir in a fixed-dose combination – and AbbVie’s recently approved four drug regimen Viekirax (ombitasvir, paritaprevir and ritonavir) and Exviera (dasabuvir).
“While substantial strides have been made in the battle against hepatitis C, a significant number of patients with complicated disease and treatment histories need additional treatment options,” said Douglas Manion, head of specialty development at BMS.
The daclatasvir/sofosbuvir data is not the first to show high cure rates in HCV/HIV co-infection. Last year, a study reported in the Journal of the American Medical Association (JAMA) last year showed that the combination of sofosbuvir with generic ribavirin was also effective in curing HCV in co-infected patients, although less so than daclatasvir/sofosbuvir, with cure rates of 67% to 76%.
Meanwhile, Gilead is also making headway in the co-infected population, reporting this week at the annual Conference on Retroviruses and Antiretroviral Infections (CROI 2015) in Seattle that Harvoni achieved a 96% cure rate at 12 weeks in the phase III ION-4 trial.
Gilead said it plans to file for approval of Harvoni in co-infected patients in the US later this year, but already has a green light for this indication in Europe. The sofosbuvir/ribavirin combination is already considered on-label in the US within Sovaldi’s registration.