Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) has decided that Gilead's new hepatitis C treatment Epclusa showed indications of additional benefit in two out of 10 treatment situations that it evaluated.
Implications | IQWiG saw added benefits from Epclusa in patients with genotypes 2 and 3, two of the patient groups that are most likely to benefit from the drug as opposed to existing interferon-free treatments. |
Outlook | The fact that IQWiG found indications for added benefit in patient groups in which Epclusa could be expected to be used more often is positive for Gilead, although the producer would hope that the G-BA would widen the scope of the patient groups for which additional benefits are accorded when it makes its final decision in around three months. |
On 17 October, Germany's Institute for Quality and Efficiency in Healthcare (IQWiG) published its dossier evaluation for the Gilead Sciences (US) drug Epclusa (sofosbuvir + velpatasvir) in the treatment of chronic hepatitis C virus (HCV). The Federal Joint Committee (G-BA) identified 10 different treatment situations (comprising eight patient groups, of which two were subdivided into two) in which the added benefit of the drug could be assessed, depending on the genotype of the virus and whether cirrhosis is present – and if so, if it is compensated or decompensated. In many cases, the appropriate comparator therapy identified was another Gilead drug – either Sovaldi (sofosbuvir) in combination with ribavirin, or Harvoni (sofosbuvir + ledipasvir) with or without ribavirin. The full list of treatment situations and appropriate comparators chosen by the G-BA can be found on the second page of IQWiG's dossier evaluation, which can be accessed here , in German.
Indication of considerable added benefit for genotype 2 (no or compensated cirrhosis)
IQWiG decided that Epclusa showed indications of an added benefit in just two of the treatment situations identified. In patients with genotype 2 HCV, without cirrhosis or with compensated cirrhosis, IQWiG decided that Epclusa showed an indication of a considerable additional benefit over the appropriate comparator – sofosbuvir plus ribavirin. IQWiG decided that the drug demonstrated an indication of an additional benefit for male patients in terms of sustained virologic response (SVR), which was seen as an adequately valid surrogate endpoint of the patient-relevant endpoint of hepatocellular carcinoma (although this was not the case for female patients). There were improvements in the side effects of tiredness and psychiatric disorders for men and women.
Indication of unquantifiable added benefit for genotype 3
IQWiG perceived an indication of an unquantifiable additional benefit in patients with genotype 3 HCV. Again, the appropriate comparator therapy was sofosbuvir plus ribavirin. The significance of the results was compromised, according to IQWiG, by the fact that in the Epclusa arm of the ASTRAL-3 study, which formed the basis of the submitted results, patients received a 12-week treatment course, while the comparator arm received a 24-week treatment course. Nevertheless, IQWiG saw that there was an advantage for Epclusa over the comparator in terms of SVR, and there was an indication that Epclusa also had an advantage for the endpoint of treatment cessation due to unwanted events.
IQWiG finds no added benefit in other groups, owing to lack of appropriate data
In the case of patients with genotype 1 or genotype 4 without cirrhosis, the producer submitted unadjusted historical comparisons, and IQWiG stated that only when the observed results were sufficiently significant could an additional benefit be derived from such studies. However, in this case, the results were not sufficiently significant, IQWiG decided.
In other treatment situations, IQWiG reports that the producer submitted data, but that these were matched with the appropriate comparator, and therefore it was not possible to assess additional benefit.
The summary of IQWiG's dossier evaluation can be accessed here, in German.
Outlook and implications
Epclusa was granted marketing authorisation in the European Union in July, and has been recommended for reimbursement by the United Kingdom's National Institute for Health and Care Excellence, as well as approved for reimbursement in Sweden.
The fact that IQWiG has recognised an additional benefit for patients with genotypes 2 and 3 ties in with the understanding that these are two of the patient populations in which Epclusa will have the greatest impact. The possibility that many patients with these genotypes could take just one pill if treated with Epclusa is a strong point in its favour. However, in Europe, the United States, and Japan, these genotypes are rarer, which could limit the number of patients likely to be prescribed Epclusa instead of existing interferon-free regimens.
The G-BA will make its final decision on the early benefit assessment of the drug in around three months, with the producer now able to submit additional information in support of its application.