Date: 2017-07-18
Type of information: Granting of a Market Authorisation in the EU
Product name: Vosevi®
Compound: sofosbuvir, velpatasvir (GS-5816) and voxilaprevir (GS-9857)
Therapeutic area: Infectious diseases
Action mechanism:
- direct-acting antiviral agent/RNA polymerase (NS5B) inhibitor/ nonstructural protein 5A (NS5A) inhibitor/ NS3/4A protease inhibitor. Vosevi® is a fixed-dose combination of two previous approved direct-acting antivirals - sofosbuvir and velpatasvir - and a new one, voxilaprevir.
- Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication.
- Velpatasvir (GS-5816) is a second-generation investigational NS5A inhibitor.
- Voxilaprevir (GS-9857) is an investigational NS3/4A protease inhibitor.
- The FDA granted this application Priority Review and Breakthrough Therapy designations.
Company: Gilead Sciences (USA - CA)
Disease: chronic hepatitis C
Latest news:
- • On July 18, 2017, the FDA approved Vosevi® to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with mild cirrhosis. Vosevi® is the first treatment approved for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A.
- The safety and efficacy of Vosevi® was evaluated in two Phase 3 clinical trials (POLARIS-1 and POLARIS-4) that enrolled approximately 750 adults without cirrhosis or with mild cirrhosis. The first trial compared 12 weeks of Vosevi® treatment with placebo in adults with genotype 1 who had previously failed treatment with an NS5A inhibitor drug. Patients with genotypes 2, 3, 4, 5 or 6 all received Vosevi®.
- The second trial compared 12 weeks of Vosevi® with the previously approved drugs sofosbuvir and velpatasvir in adults with genotypes 1, 2 or 3 who had previously failed treatment with sofosbuvir but not an NS5A inhibitor drug.
- Results of both trials demonstrated that 96-97 percent of patients who received Vosevi® had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.
- Treatment recommendations for Vosevi® are different depending on viral genotype and prior treatment history. The most common adverse reactions in patients taking Vosevi® were headache, fatigue, diarrhea and nausea.
- Vosevi® is contraindicated in patients taking the drug rifampin.
- Vosevi® has a boxed warning in its product label regarding the risk of hepatitis B virus (HBV) reactivation in HCV/HBV coinfected patients. Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. HBV reactivation in patients treated with direct-acting antiviral medicines can result in serious liver problems or death in some patients. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Vosevi®. See below for important safety information.
- • On June 22, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Vosevi®, for the treatment of chronic hepatitis C. The drug was reviewed under EMA’s accelerated assessment programme. It will be available as film-coated tablets (containing 400 mg sofosbuvir, 100 mg velpatasvir and 100 mg voxilaprevir).
- Vosevi® is highly effective against all genotypes of HCV and can be used in patients in whom prior treatment with other direct-acting antivirals has failed. The most common side
effects are headache, diarrhoea and nausea.
- The MAA for Vosevi® is supported by data from four Phase 3 studies. POLARIS-1 and POLARIS-4 evaluated 12 weeks of the single tablet regimen in patients with genotypes 1-6 HCV infection previously treated unsuccessfully with direct-acting antiviral agent-containing regimens, including NS5A inhibitors. POLARIS-2 and POLARIS-3 evaluated 8 weeks of SOF/VEL/VOX in DAA-naïve patients with genotypes 1-6 HCV infection.
- Across POLARIS-1 and POLARIS-4, 97 percent of patients treated with SOF/VEL/VOX (n=431/445) achieved the primary efficacy endpoint of SVR12. In POLARIS-2, 95 percent of patients with genotypes 1-6 HCV infection with and without cirrhosis treated with SOF/VEL/VOX (n=477/501) achieved the primary efficacy endpoint of SVR12. In POLARIS-3, 96 percent of patients with genotype 3 infection and cirrhosis treated with SOF/VEL/VOX (n=106/110) achieved the primary efficacy endpoint of SVR12. The most common adverse events among patients who received SOF/VEL/VOX in the POLARIS studies were headache, fatigue, diarrhea and nausea.
- Gilead has also submitted a regulatory application for SOF/VEL/VOX in the United States . Gilead filed the New Drug Application for SOF/VEL/VOX on December 8, 2016 , and the FDA has set a target action date under the Prescription Drug User Fee Act of August 8, 2017 .
Patents:
Submission of marketing authorization application USA : 2016-12-08
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-07-18
UE authorization: 2017-07-26
Favourable opinion UE: 2017-06-22
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
