Type of information: Granting of a Market Authorisation in Japan
Product name: Sovaldi®
Therapeutic area: Infectious diseases
Action mechanism: nucleotide NS5B polymerase inhibitor. Sofosbuvir is a nucleotide NS5B polymerase inhibitor. NS5B is a specific protein needed by the hepatitis C virus to replicate. This drug is the first representative of this new class of antivirals that act as inhibitors of an essential enzyme of HCV, the NS5B ribonucleic acid polymerase.
Company: Gilead Sciences (USA - CA)
Disease: chronic hepatitis C in adults
- • On March 26, 2015, Gilead Sciences announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Sovaldi® (sofosbuvir) for the suppression of viremia in patients with genotype 2 chronic hepatitis C virus (HCV) infection with or without compensated cirrhosis. Sovaldi® is indicated for use in combination with ribavirin (RBV) for 12 weeks. Sovaldi (in combination with RBV) is the first all-oral, interferon-free treatment regimen for genotype 2 HCV infection. Sovaldi® is also the first product to be marketed by Gilead in Japan .
- Sovaldi®'s approval is supported by data from a Phase 3 clinical trial conducted in Japan (Study GS-US-334-0118) among treatment-naïve and treatment-experienced genotype 2 patients. Approval was based on 96 percent (n=135/140) of genotype 2 HCV-infected patients who received 12 weeks of an all-oral regimen of Sovaldi plus RBV 600-1,000 mg/day achieving a sustained virologic response 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV infection. The approval is also supported by SVR12 results from four international Phase 3 studies (FISSION, FUSION, POSITRON and VALENCE), which included genotype 2 HCV patients.
- • On June 27, 2014, Gilead has submitted an NDA to Japan's PMDA for sofosbuvir as a single agent in combination with ribavirin for the treatment of genotype 2 HCV infection.
- • On January 17, 2014, Gilead Sciences has announced that the European Commission has granted marketing authorization for Sovaldi® (sofosbuvir) 400 mg tablets for the treatment of chronic hepatitis C (CHC) infection in adults, in combination with other antiviral agents (ribavirin (RBV) and pegylated interferon alpha (peg-IFN)). Sovaldi® has been studied in hepatitis C virus (HCV) genotypes 1-6. The efficacy of Sovaldi® has been established in patients with genotypes 1-4, in those awaiting liver transplantation and those with HCV/HIV-1 co-infection. The clinical data supporting the use of Sovaldi in patients with genotypes 5 and 6 is limited.
- • On December 6, 2013, the FDA has approved Sovaldi® (sofosbuvir) to treat chronic hepatitis C virus (HCV) infection. Sovaldi® is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon. Sovaldi® is to be used as a component of a combination antiviral treatment regimen for chronic HCV infection. Depending on the type of HCV infection a patient has, the treatment regimen could include Sovaldi® and ribavirin or Sovaldi®, ribavirin and peginterferon-alfa.
- Sovaldi®’s effectiveness was evaluated in six clinical trials consisting of 1,947 participants who had not previously received treatment for their disease (treatment-naive) or had not responded to previous treatment (treatment-experienced), including participants co-infected with HCV and HIV. The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s HCV infection has been cured. Results from all clinical trials showed a treatment regimen containing Sovaldi was effective in treating multiple types of the hepatitis C virus. Additionally, Sovaldi® demonstrated efficacy in participants who could not tolerate or take an interferon-based treatment regimen and in participants with liver cancer awaiting liver transplantation, addressing unmet medical needs in these populations.
- The most common side effects reported in clinical study participants treated with Sovaldi and ribavirin were fatigue and headache. In participants treated with Sovaldi, ribavirin and peginterferon-alfa, the most common side effects reported were fatigue, headache, nausea, insomnia and anemia. Sovaldi® is the third drug with breakthrough therapy designation to receive FDA approval.
- • On November 22, 2013, the European Medicines Agency's Committee for Medicinal Products for Human use (CHMP) has recommended granting a marketing authorisation for Sovaldi® (sofosbuvir), for use in combination with other medicinal products for the treatment of chronic (long-term) hepatitis C in adults. Sovaldi® provides the first interferon-free treatment option for chronic hepatitis C. In clinical trials where sofosbuvir was used in combination with ribavirin alone, it has convincingly shown efficacy with a good safety profile. A high proportion of patients had no detectable virus in their blood 12 to 24 weeks after the end of the treatment and could therefore be considered to be cured of their hepatitis C virus infection.
- When Sovaldi® is used in combination with pegylated interferon as well as ribavirin, shortened treatment duration down to 12 weeks (compared to 24-48 weeks with the current standard of care) is possible and provides high efficacy. This is of value considering the side-effect profile of interferon. During its October 2013 meeting, the CHMP gave an opinion on the conditions under which early access to sofosbuvir, in combination with other medicines, could be given in compassionate-use programmes, for patients with chronic hepatitis C infection before or after liver transplantation. Such programmes, set up at the national level, are intended to give patients with a life-threatening, long-lasting or seriously disabling disease who have no available treatment options access to treatments that are still under development and that have not yet been authorised. During its November meeting, the CHMP also provided an opinion on the use of a combination of sofosbuvir with the antiviral daclatasvir in certain patients with chronic hepatitis C virus (HCV) infection, in a compassionate-use programme.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2013-12-06
UE authorization: 2014-01-17
Favourable opinion UE: 2013-11-22
Favourable opinion USA: 2013-10-25
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
Other news: • On July 26, 2017, Mylan announced receipt of approval from the World Health Organization Prequalification of Medicines Program (WHO PQ) of its application for sofosbuvir tablets, 400 mg, a generic version of Gilead Sciences' Sovaldi®. Sofosbuvir, a directly acting antiretroviral, will be available in developing countries to treat hepatitis C. Mylan's Sofosbuvir Tablets, 400 mg, which are produced under license from Gilead Sciences, are the first generic version to be approved under the WHO PQ Program. With WHO PQ approval, international donors and purchasers, such as UNITAID and U.N. agencies, will able to fund and procure the product, and other buyers can be assured of the product's quality, safety and efficacy.