The German Institute for Quality and Efficiency in Health Care (IQWiG) is an independent scientific institute that analyzes the benefits and dangers of medical interventions for patients. Recently they examined the dossier assessment of the drug combination of ledipasvir and sofosbuvir, commercialized as Harvoni, and available since November 2014 as therapy for chronic hepatitis C infection. This assessment is part of the early benefit assessment of the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA).

The IQWiG examined the dossier to assess if the drug combination of ledipasvir and sofosbuvir offered an added benefit over the appropriate comparator therapy. IQWiG examined the added benefit of this drug combination in 7 different patient groups divided based on the genotype of the hepatitis C virus (1, 3, or 4), stage of the disease and previous treatment. They report that the drug manufacturer did not show direct comparative studies, but only historical comparisons, i.e. data from different studies, where at least one of the treatments to be compared was tested are compared.

IQWiG found a non-quantifiable added benefit for 2 out of 7 patient groups. In an infection with genotype 1 hepatitis C virus (HCV) when prior treatments had no success and previous untreated patients still did not develop cirrhosis of the liver, the data showed an advantage in sustained virology response (SVR). After the therapy, the majority of the patients were free of the virus, while in the comparator therapies the success rate was only between almost 35% and 75%. The difference between the therapies used in the historical comparisons seemed so big that the clinical benefit observed for the new drug combination could be just due to this difference.

IQWiG found an indication of an added benefit only in 2 of the 3 genotype 1 groups, particularly in patients under treatment with and without infection and without cirrhosis of the liver. Still, the level of this added benefit is not quantified. It remained unclear how many patients without detectable virus will not develop liver cancer.

For the other 4 patient groups, HCV genotype 4 and 3 and decompensated cirrhosis of the liver, IQWiG did not find any added benefit of the combination drug. For patients with genotype 1 HCV also infected with HIV, the manufacturer presented comparative data but it was incomplete.

IQWiG concluded that because of reduced certainty of the dossier conclusions, no more than a “hint” can be drawn from these type of data.

The Federal Joint Committee (G-BA) will perform a commenting procedure after the publication of the dossier assessment and gives a final decision on the extension of the added benefit for the drug combination of ledipasvir and sofosbuvir.