The European Commission has granted marketing authorization for Epclusa ( Sofosbuvir 400 mg / Velpatasvir 100 mg ), the first pan-genotypic, single tablet regimen for the treatment of adults with genotype 1-6 chronic hepatitis C virus ( HCV ) infection.
The combination of Sofosbuvir and Velpatasvir ( SOF/VEL ) for 12 weeks was authorized for use in patients without cirrhosis or with compensated cirrhosis ( Child-Pugh A ), and in combination with Ribavirin ( RBV ) for patients with decompensated cirrhosis ( Child-Pugh B or C ).
SOF/VEL is also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for Ribavirin.
Physicians also have the flexibility to consider the addition of Ribavirin for genotype 3 infected patients with compensated cirrhosis.
Sofosbuvir and Velpatasvir is third Sofosbuvir-based treatment to be granted Marketing Authorization by the European Commission for the treatment of chronic HCV infection.
Sofosbuvir-based regimens are recommended by global guidelines across all HCV genotypes and disease severities. Today, nearly one million patients worldwide have been prescribed a Sofosbuvir-based regimen.
The authorization of Sofosbuvir and Velpatasvir is supported by data from four phase 3 studies, ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4.
In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,035 patients with genotypes 1-6 HCV infection, without cirrhosis or with compensated cirrhosis ( Child-Pugh A ) received 12 weeks of SOF/VEL.
The ASTRAL-4 study randomized 267 patients with genotypes 1-6 HCV infection, with decompensated cirrhosis ( Child-Pugh B ) to receive 12 weeks of SOF/VEL with or without Ribavirin or 24 weeks of SOF/VEL alone.
The primary endpoint for all studies was the sustained viral response rate 12 weeks after treatment ( SVR12 ).
Of the 1,035 patients treated with Sofosbuvir and Velpatasvir for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 ( 98% ) achieved SVR12.
In ASTRAL-4, patients with decompensated cirrhosis receiving SOF/VEL with Ribavirin for 12 weeks achieved a higher SVR12 rate ( 94% ) compared to those who received SOF/VEL for 12 weeks or 24 weeks without Ribavirin ( 83% and 86%, respectively ).
The most common adverse events in the four ASTRAL studies were headache, fatigue and nausea, and were comparable in incidence to the placebo group included in ASTRAL-1.
Sofosbuvir as a single agent was granted marketing authorization in the European Union on January 16, 2014 under the trade name Sovaldi.
The fixed-dose combination of Sofosbuvir ( 400 mg ) and Ledipasvir ( 90 mg ) received marketing authorization in the European Union on November 18, 2014 under the trade name Harvoni.
Contraindications include hypersensitivity to the active substances or to any of the excipients. Co-administration with potent P-glycoprotein ( P-gp ) or potent cytochrome P450 ( CYP ) inducers ( e.g. Rifampicin, Rifabutin, St. John’s wort [ Hypericum perforatum ], Carbamazepine, Phenobarbital and Phenytoin ) is contraindicated.
Caution and frequent renal monitoring is recommended for co-administration with certain HIV antiretroviral treatments ( e.g. Tenofovir disoproxil fumarate- and Efavirenz-containing regimens ).
Safety has not been established in patients with severe renal impairment ( glomerular filtration rate less than 30ml/min ).
Monitoring of Digoxin, Dabigatran and Amiodarone is recommended when used with Sofosbuvir / Velpatasvir. For patients on statins dose reduction should be considered and careful monitoring for statin adverse events ( myopathy and rhabdomyolysis ) should be undertaken.
In clinical studies, adverse events were comparable to placebo, with fatigue, headache and nausea the most commonly reported side effects. ( Xagena )
Source: Gilead, 2016