AMSTERDAM – Despite the transformative impact of direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV), reimbursement for the drugs still faces "considerable restrictions" in Europe, according to research presented Thursday at the International Liver Congress, suggesting that an early challenge for key drugmakers in the space, such as Gilead Sciences Inc. and Abbvie Inc., still endures.

"The availability of simple, tolerable DAA-based therapies for HCV with high cure rates is one of the greatest clinical advances in recent decades," said Alison Marshall, a doctoral candidate at Kirby Institute in Australia's University of New South Wales. Marshall and her colleagues found that most European countries reimbursed some form of DAA treatment, but that restrictions based on fibrosis stage, drug or alcohol use, and especially the necessity of a specialist prescriber (vs. a general practitioner, or GP), still persist.

Marshall told BioWorld Today that she anticipates her group's review will help facilitate dialogue between health care practitioners and policymakers. That could potentially facilitate a movement to open up prescribing authorization to GPs in rural areas already serving populations at high risk for HCV, such as injectable drug users, potentially improving access, something that could be good for both patients and drugmakers.

The restrictions are "widespread and conflicting" with treatment guidelines issued by the European Association for the Study of the Liver (EASL), preventing many patients from being treated, said EASL governing board member Francesco Negro, who is also professor at the University Hospital of Geneva.

The high cost of DAAs has meant restrictions on access from day one worldwide. That has made it a big topic for Gilead, which has had success in opening up access for patients with lower liver fibrosis scores, but still faces payer resistance in the form of requirements for prior authorizations. As a result, doctors can sometimes shy away from prescribing DAAs.

During the February's RBC Capital Markets Healthcare Conference, Gilead CEO John Milligan underscored the issue. "Each country in Europe has a slightly different dynamic. Some are more cost-conscious and some are more scientifically driven," he said. In areas that are less scientifically driven, Milligan estimated that "we're a little bit more vulnerable to a competitor like Merck [& Co. Inc.], and sometimes we'll lose some market share. Our market share in the United States, which is more scientifically driven, still remains very high, north of 85 percent." In Europe, he estimated, the company's share is closer to 70 percent.

The review examined online reimbursement data covering November 2016 to March 2017. It found that the most common DAAs reimbursed in Europe were Abbvie Inc.'s Viekirax (ombitasvir/paritaprevir/ritonavir), followed by Gilead's Harvoni (ledipasvir/sofosbuvir). For treatment-naïve patients, 38 percent of European countries with complete data required evidence of at least moderate fibrosis (greater than or equal to F2) before DAAs were prescribed. Nearly a quarter of countries required at least severe fibrosis (greater than or equal to F3). Almost a fifth of European countries had a drug or alcohol use limitation requirement. Further, 94 percent of countries required specialists to prescribe DAA therapy.

The picture was not all bad. Marshall's group found that more than a quarter of the 34 countries with complete data put no fibrosis stage requirements on treatment, and said that fibrosis stage requirements are rapidly changing across Europe. Also, more than three-quarters of the countries had no substance use restrictions and almost all the countries had no additional restrictions related to HIV-HCV co-infections.

Despite the disparities in reimbursement requirements across the continent, Marshall also suggested that reviews such as her group's might inform discussions about the development of national strategies to combat HCV. That's a conversation that drugmakers will no doubt be eager to advise upon.