Having had no new drugs for hepatitis C since ribavirin’s approval more than a decade ago, doctors will shortly be spoilt for choice.
A wave of new products are emerging from R&D pipelines, with more than 30 companies developing scores of novel antivirals. At the European Association for the Study of the Liver (EASL) annual congress in Berlin, which ended yesterday (April 3), Mark Thursz of Imperial College, London and vice-secretary of EASL reviewed what to look out for.
The two front runners are both protease inhibitors (PIs) - Victrelis (boceprevir) from Merck & Co and telaprevir from Vertex, Tibotec and Mitsubishi Tanabe Pharma. Launches of both drugs are expected this year and snapping at their heels are second generation PIs such as Boehringer Ingelheim’s BI 201335 – an oral once-daily offering which has just moved into Phase III and been fast-tracked by the US Food and Drug Administration.
Boceprevir is given three times a day; telaprevir every eight hours. Asked how clinicians would choose between the two PIs, Prof Thursz said that although there was no head-to-head data, the products differed in their side effect profiles: “With boceprevir there is more anaemia and dysgeusia (foul taste in the mouth) and with telaprevir, the main side effect is a rash which some patients may not be able to tolerate.”
Overall, he said that results with the new PIs were “remarkable”, offering unprecedented levels of sustained virological response, however the drugs still need to be given against a relatively toxic ‘back-bone’ of pegylated interferon-alfa plus ribavirin. For him, the "light at the end of the tunnel" would be an interferon-free regimen, such as combination therapy with a PI plus an NS5b-polymerase or NS5a inhibitor.
Boehringer’s HCV polymerase inhibitor BI 207127 has been FDA- fast-tracked in combination with the German firm’s aforementioned BI 201335. Bristol-Myers Squibb is trialling its PI, BMS 650032, in combination with the NS5A inhibitor BMS 790052 – albeit in a quadruple regimen with PEG-IFN/ribavirin.
Prof Thursz sounded a note of caution about potential resistance to PIs. “We are going to face a problem with resistant variants,” he said. “These new drugs will need to be handled by specialists who have some understanding of these patterns of resistance and their future implications.”
Patients not getting proper treatment
He concluded that despite ‘fantastic’ new drugs upcoming for hepatitis C, they would have little impact on the global burden of this potentially eradicable disease unless health policies change (up to 170 million people are estimated to be infected with the virus). France has the highest rates of treatment in the European Union, but even there only 16% of hepatitis C patients currently receive treatment. “In the UK, I am embarrassed to say, only 3% of our hepatitis C patients receive treatment. We cannot expect to have much of an impact if we do not screen and treat patients and get rid of the virus,” he said.
In other presentations, early data from Phase I trials of an HCV vaccine were unveiled. Two studies flagged by EASL reported high immunogenicity and good safety profile for a novel T-cell vaccine based on adenovirus vectors (abstracts 750 and 2104). The therapeutic vaccine is being developed by a team at the University of Oxford, UK.