The FDA has approved ocrelizumab (Ocrevus – Genentech), a humanized anti-CD20 monoclonal antibody, for treatment of adults with primary progressive or relapsing multiple sclerosis (MS). It is the first anti-CD20 monoclonal antibody to be approved for treatment of MS and the first disease-modifying drug to be approved in the US for primary progressive MS.

The FDA has approved daclizumab (Zinbryta – Biogen/Abbvie), an interleukin-2 (IL-2) receptor blocking monoclonal antibody, for treatment of adults with relapsing forms of multiple sclerosis (MS). It is the first subcutaneously injected monoclonal antibody to be approved for treatment of MS.

Most patients with multiple sclerosis (MS) present with the relapsing-remitting form of the disease. Treatment usually includes disease-modifying drugs, various other drugs for managing symptoms such as fatigue, depression, and pain, and corticosteroids for acute exacerbations.

Harvoni, a once-daily fixed-dose combination of the direct-acting antiviral agents ledipasvir and sofosbuvir approved by the FDA in 2014 for treatment of hepatitis C virus (HCV) genotype 1 infection,1 has now been approved for use in patients infected with HCV genotype 4, 5, or 6, and in patients co-infected with HCV and HIV-1. A 12-week course of treatment with Harvoni plus ribavirin has also been approved as an alternative to 24 weeks of Harvoni alone for treatment-experienced, cirrhotic patients with HCV genotype 1 infection.

HCV genotypes 4, 5, and 6 are responsible for <2% of HCV cases in the US and Canada. They are more prevalent in the Middle East, North Africa, and Central sub-Saharan Africa (genotype 4), Southern sub-Saharan Africa (genotype 5), and Southeast Asia (genotype 6).2

In two open-label trials (both summarized in the package insert), 44 patients infected with HCV genotype 4, 41 patients with genotype 5, and 25 patients with genotype 6 received 12 weeks of treatment with ledipasvir/sofosbuvir.3 The rates of sustained virologic response 12 weeks after stopping treatment (SVR12) were 93%, 93%, and 96% in patients infected with HCV genotypes 4, 5, and 6, respectively.

In a single-arm trial (ION-4), 335 patients co-infected with HIV-1 and HCV genotype 1 (98%) or 4 (2%) received 12 weeks of treatment with ledipasvir/sofosbuvir. An SVR12 was achieved in 322 patients (96%), including 94% of 67 cirrhotic patients and 97% of 185 treatment-experienced patients.4

In a randomized, double-blind trial (SIRIUS), 154 treatment-experienced patients with HCV genotype 1 infection and cirrhosis who had not responded to peginterferon plus ribavirin with and without a protease inhibitor received either ledipasvir/sofosbuvir plus ribavirin 1000-1200 mg daily for 12 weeks or ledipasvir/sofosbuvir without ribavirin for 24 weeks. An SVR12 was achieved in 74 of 77 patients (96%) in the 12-week arm and in 75 of 77 patients (97%) in the 24-week arm.5

1. A combination of ledipasvir and sofosbuvir (Harvoni) for hepatitis C. Med Lett Drugs Ther 2014; 56:111.
2. JP Messina et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61:77.
3. EJ Gane et al. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology 2015; 149:1454.
4. S Naggie et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med 2015; 373:705.
5. M Bourlière et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015; 15:397.

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The FDA has approved daclatasvir (Daklinza – BMS), an oral direct-acting antiviral drug, for use with sofosbuvir (Sovaldi) for treatment of chronic hepatitis C virus (HCV) genotype 3 infection. Daclatasvir is the first drug approved for this indication that does not require the addition of interferon or ribavirin. It is approved in Japan and Europe in combination with other drugs for treatment of HCV genotypes 1-4.

The FDA has approved a pegylated form of interferon beta-1a (Plegridy – Biogen) for biweekly treatment of patients with relapsing multiple sclerosis (MS).

The FDA has approved the nucleotide polymerase inhibitor sofosbuvir (Sovaldi – Gilead) for use in combination with other antiviral drugs for treatment of chronic hepatitis C virus (HCV) infection.

The FDA has recently approved 2 new drugs for treatment of chronic hepatitis C virus (HCV) infection. Simeprevir (Olysio – Janssen) is the third oral protease inhibitor to be approved for use in combination with peginterferon and ribavirin for treatment of chronic HCV genotype 1 infection in adults with compensated liver disease. Telaprevir (Incivek) and boceprevir (Victrelis) were approved in 2011 for the same indication. Sofosbuvir (Sovaldi – Gilead), a nucleotide analog polymerase inhibitor that has been approved for use with and without interferon for treatment of multiple HCV genotypes, will be reviewed in the next issue of The Medical Letter.

Telaprevir (Incivek – Vertex) and boceprevir (Victrelis – Merck) have been approved by the FDA for oral use in combination with peginterferon and ribavirin for treatment of chronic hepatitis C virus (HCV) genotype 1 infection in adults with compensated liver disease. Both telaprevir and boceprevir were developed specifically to inhibit the NS3/4A proteases that cleave HCV encoded polyproteins of the genotype 1 virus.