Daclatasvir recommended for European approval

The scientific committee of the European Medicines Agency recommended the approval of daclatasvir a new direct-acting antiviral for treatment of hepatitis C virus (HCV) on 26 June. Daclatasvir is an NS5A inhibitor, which means that it stops HCV replication by blocking the action of the NS5A protein.

It has been recommended for use in the European Union in combination with other direct-acting antivirals. Full details of the licensing indication will be released when daclatasvir receives marketing approval, which is expected by mid-August or early September. Daclatasvir has been developed by Bristol-Myers Squibb and will be marketed under the brand name Daklinza in the European Union.

A two-drug combination of daclatasvir and asunaprevir was approved in July for the treatment of genotype 1 infection in Japan where approximately 70% of people with hepatitis C have genotype 1b infection. This two-drug combination is potent for genotype 1b, but less efficient for the 1a subtype.

Daclatasvir is the first NS5A inhibitor to be approved. Several other pharmaceutical companies are developing NS5A inhibitors as part of combinations of direct-acting antivirals. The European Association for the Study of the Liver (EASL) has recommended that daclatasvir may be used in combination with either sofosbuvir or with pegylated interferon and ribavirin for the treatment of HCV genotypes 1, 3 or 4. Other combination products are likely to receive European marketing approval in 2015.

Hepatitis C treatment during opioid substitution therapy

Daniel Cohen, of AbbVie, presenting at AIDS 2014. Photo by Liz Highleyman, hivandhepatitis.com.

Therapy for hepatitis C using the ‘3D’ interferon-free combination is safe and effective while taking opioid substitution therapy, a clinical trial has shown.

Some physicians take the view that it is preferable to delay hepatitis C treatment for people who inject drugs until they are taking opioid substitution therapy, on the grounds that good adherence may be more likely. Methadone or buprenorphine are prescribed as opioid substitution therapy, supporting people to stop using heroin and to stop injecting.

AbbVie’s 3D combination of direct-acting antivirals has produced very high cure rates in both previously untreated and treatment-experienced patients. AbbVie's 3D regimen consists of the HCV protease inhibitor ABT-450, a 100mg boosting dose of ritonavir and the NS5A inhibitor ombitasvir (formerly ABT-267) in a once-daily fixed-dose coformulation, taken with the twice-daily HCV polymerase inhibitor dasabuvir (ABT-333) and ribavirin. The regimen was taken for 12 weeks.

The study recruited 38 people taking opioid substitution therapy, predominantly with genotype 1a HCV infection. Almost all had mild or moderate liver fibrosis. 97% achieved a cure, defined as a sustained virologic response 24 weeks after completing treatment. The regimen was well tolerated with no evidence of negative drug interactions between hepatitis C drugs and opioid substitution therapy.

Hepatitis C treatment for people with HIV and hepatitis C co-infection

Jean-Michel Molina presents the results of PHOTON-2. Photo by Liz Highleyman, hivandhepatitis.com

The AbbVie regimen described in the previous section also proved highly successful in curing hepatitis C infection in people with HIV and hepatitis C co-infection in the TURQUOISE-1 study, presented this month at the 20th International AIDS Conference (AIDS 2014), in Melbourne.

The study enrolled both previously untreated people (about 67%) and prior relapsers (6%), partial responders (11%) and null responders (16%). About 90% had harder-to-treat HCV subtype 1a.

Participants in this open-label study were randomly assigned to take the 3D regimen plus ribavirin for either 12 or 24 weeks. The SVR12 rate (sustained virological response 12 weeks after completion of treatment) was 94% for participants in the 12-week arm. In the 24-week arm, the SVR4 rate – which is too soon to consider a cure – was 97%. Among the 20 people in this arm who had reached 12 weeks of post-treatment follow-up, the SVR12 rate was 95% and none had relapsed.

A regimen of sofosbuvir and ribavirin cured between 84 and 89% of people with genotype 1, 2, 3 or 4 hepatitis C infection, but performed less well in people with cirrhosis and genotype 1 infection, in the PHOTON-2 study also presented at the conference. A small number of previously untreated participants with HCV genotype 2 (19 people) were treated for 12 weeks, while all treatment-experienced people and everyone with harder-to-treat genotype 1 or 4 were treated for 24 weeks.

The response rates in the PHOTON trials are not particularly impressive compared to the 90 to 100% SVR12 rates seen in several other recent interferon-free studies. Sofosbuvir works better when combined with other direct-acting antivirals such as the NS5A inhibitors ledipasvir or daclatasvir (Daklinza). Presenting the results, Jean-Michel Molina suggested that sofosbuvir plus ribavirin may be a good option for people who have HIV and HCV co-infection, with genotype 2 or 3 HCV, who do not have liver cirrhosis.

Hepatitis C treatment factsheets

At the International Liver Congress, we launched three new hepatitis C treatment factsheets.

Each factsheet focuses on one direct-acting antiviral drug and gives an overview of how it works, who can use it, how it is taken, what trial results tell us about how effective it is, known side-effects and drug interactions.

The factsheets are available to read online, and are also designed to be printed and shared. Find out more in the infohep.org blog.

Customise your hepatitis information

We have also recently developed a simple tool to customise the hepatitis treatment information on infohep.org.

For example, you can choose to search for information according to the genotype it is relevant to, or information relevant for people who have taken treatment before.

Answer a few simple questions, and the information presented will be our news reporting on the studies relevant to your search.

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