Back HIV Treatment Experimental HIV Drugs Dolutegravir for HIV and Sofosbuvir for Hepatitis C Approved in Europe

Dolutegravir for HIV and Sofosbuvir for Hepatitis C Approved in Europe

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The European Commission this week approved 2 important new drugs, ViiV Healthcare's HIV integrase inhibitor dolutegravir (brand name Tivicay) and Gilead Science's nucleotide hepatitis C virus polymerase inhibitor sofosbuvir (Sovaldi).

Dolutegravir

Dolutegravir (formerly S/GSK1349572), which received U.S. Food and Drug administration (FDA) approval this past August, works by preventing HIV from inserting its genetic material into host cell chromosomes.

The Commission's approval on January 21 allows dolutegravir to be sold in each member state of the European Union. It will come on the market in each country as pricing and reimbursement processes are completed, with availability in some of the first countries "anticipated in the immediate future," according to ViiV.

Dolutegravir is indicated for use as part of combination antiretroviral therapy for adults and adolescents age 12 and older. The recommended dose for most patients is a single 50 mg tablet once daily. For people with documented or suspected integrase inhibitors resistance, or when co-administered with certain medicines, the recommended dose is 50 mg twice-daily.

Approval of dolutegravir was based on good safety and efficacy in a series of Phase 3 trials of treatment-naive and treatment-experienced patients. In the SPRING-2 trial, dolutegravir worked as well as raltegravir (Isentress) for previously untreated people with HIV. The SINGLE study showed that dolutegravir plus abacavir/lamivudine had superior antiviral efficacy compared with the Atripla single-tablet regimen (efavirenz/tenofovir/emtricitabine) for first-line HIV treatment, with fewer discontinuations due to side effects. In the SAILING trial, dolutegravir demonstrated better efficacy than raltegravir for treatment-experienced patients, with fewer discontinuations due to virological failure and less emergent drug resistance. The VIKING trials showed that dolutegravir is effective against HIV that has developed resistance to multiple classes of other antiretrovirals.

"HIV treatment is not a question of 'one-size fits all' -- especially now that treatment is something that patients will live with for many years," said ViiV Chief Medical Officer John Pottage in a company press release. "We continue to find measurable clinical differences among the treatments now available for use in combination therapy to combat HIV. Using the clinical data for Tivicay, doctors and people living with HIV can fully consider the effectiveness against the virus and the side effect profile that Tivicay may bring."

ViiV's press release, which includes Important Safety Information for Tivicay, is available online.

Sofosbuvir

Sofosbuvir (formerly known as GS-7977 and PSI-7977), approved by the FDA in early December, is the first approved HCV polymerase inhibitor and a component of the first all-oral regimen: sofosbuvir plus ribavirin for treatment of chronic hepatitis C patients with HCV genotype 2 or 3, or people with genotype 1 who cannot tolerate interferon.

The European Commission approved sofosbuvir for treatment of HCV genotypes 1-6, though there is little data on 5 or 6. It was approved for use with pegylated interferon and ribavirin for 12 weeks for adults with genotypes 1, 4, 5, or 6. Those who cannot tolerate interferon may use sofosbuvir and ribavirin alone for 24 weeks.

The indication for HCV genotype 2 is sofosbuvir plus ribavirin for 12 weeks, while people with harder-to-treat genotype 3 should receive the 2-drug regimen for 24 weeks. The dual oral regimen was also approved for patients awaiting liver transplantation. These indications are the same for people with HIV/HCV coinfection.

Sofosbuvir demonstrated high rates of sustained virological response at 12 or more weeks post-treatment -- considered a cure -- in the Phase 3 NEUTRINO, FISSION, POSITRON, FUSION, VALENCE, and PHOTON-1trials. It has demonstrated good efficacy both in combination with pegylated interferon/ribavirin and in all-oral regimens with ribavirin alone. It has also demonstrated promising results with other direct-acting antivirals including daclatasvirledipasvir, and simeprevir. Gilead is now developing a coformulation of sofosbuvir and ledipasvir.

"Unlike many chronic diseases, hepatitis C can be cured. However, for a number of reasons, many HCV patients have not currently achieved a cure and often progress to end-stage liver disease or liver cancer," said Graham Foster, Professor of Hepatology at Queen Mary University of London, in a Gilead press release. "With high cure rates across a broad range of patients and a short duration of therapy, Sovaldi is a very welcome therapeutic advance that will increase the number of patients who can be treated and ultimately cured."

Gilead's press release announcing the approval is also available online.

1/23/14

Sources

ViiV Healthcare. ViiV Healthcare’s new HIV medicine Tivicay (Dolutegravir) is Approved in Europe. Press release. January 21, 2014.

Gilead Sciences. European Commission Grants Marketing Authorization for Gilead’s Sovaldi (Sofosbuvir) for the Treatment of Chronic Hepatitis C Infection. Press release. January 17, 2014.