Novartis' investigational oral agent alisporivir cured almost 50% more previously untreated patients with the most common form of hepatitis C when added to a standard treatment regimen, according to Phase II data presented at the European Association for the Study of the Liver congress in Berlin.
The data were described as “fantastic” by EASL vice secretary Mark Thursz, professor of hepatology at Imperial College, London, while Robert Flisiak from the Medical University of Bialystok, Poland, told the congress: “This novel agent has the potential to be an important component of future hepatitis C treatment.”
The ESSENTIAL study involved 300 previously untreated patients infected with genotype 1 HCV. Of those treated with alisporivir, plus standard of care (pegylated-interferon alfa 2a/ribavirin), 76% achieved superior viral cure compared to 55% of patients on standard care alone 24 weeks after stopping treatment.
The study’s principal investigator, Stefan Zeuzem from Goethe University Hospital in Frankfurt, said: “Hepatitis C is difficult to treat and current therapies are effective only in about half of patients with the most prevalent genotype. These results are exciting because a large majority of patients achieved sustained viral response with alisporivir.”
Alisporivir is the first in a new class of drugs called cyclophilin inhibitors. Unlike other compounds in development that target the hepatitis C virus directly, alispirovir, targets host proteins that the hepatitis C virus uses for replication.
A Phase IIb trial looking at the potential of the agent in HCV patients with genotypes 2 and 3 is underway. The host proteins are needed for replication in all types of HCV infection so there is potential for the agent to have broad activity; there are six variations of HCV.
Phase III trial underway
An international Phase III study is now underway to evaluate the efficacy and safety of alisporivir combined with standard care in previously untreated HCV G1 patients. The Phase II study showed that serious adverse events occurred in 6.9% of patients treated with alispirovir and standard care compared to 5.5% of patients treated with standard care alone. Prof Flisiak reported a higher rate of bilirubin (32.9% versus 1.4% in the alisporivir-treated group compared to standard care alone) but this was transient and reversible and associated with the initial loading dose. Final data from the Phase III ESSENTIAL-2 is expected in March 2013.
Novartis medical director Nikolai Naoumov told Pharma Times World News: “The data is very encouraging because it has produced a significant response in the most common form of HCV which can be very difficult to treat and with a reasonable safety profile. If the results of Phase III and other studies are also encouraging, this agent could offer a paradigm shift in clinical practice by being able to treat a number of genotypes and patients who have not responded to standard care.”
Novartis in-licensed alisporivir, also known as DEB025, from fellow Swiss firm Debiopharm in February 2009.