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New HCV Oral Interferon-Free Regimens
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On Oct 10 the FDA Approved Gilead's Harvoni, a fixed dose single tablet combination pill regimen that contains sofosbuvir & ledipasvir.
Sometime soon, expected by December 2014 it's expected the FDA will also approve Abbvie's 3D oral interferon-free pill regimen which contains 3 drugs - The 3D regimen includes Ombitasvir (ABT-267) an NS5A inhibitor, ABT450, a NS3/4A protease inhibitor coadministered with low dose ritonavir which as in HIV with Kaletra significantly increases drug levels of ABT450 - increases peak, trough & over all drug exposures of ABT450/r, and Dasabuvir (ABT-333), a nonnucleoside NS5B RNA polymerase inhibitor. Ombitasvir & ABT-450/r are coformulated as a single tablet.
As well it's expected the FDA will approve around this time Janssen's Supplemental New Drug Application for Simeprevir+Sofosbuvir. BMS issued a statement on Oct 8 about the New Drug Application announcing they withdrew their application (see statement below) which they had previously submitted to the FDA for daclatasvir+asunaprevir. Still the BMS three phase 3 studies of daclatasvir+sofosbuvir are ongoing, they started early in 2014 & are expected to have FDA review for approval in 2015 (see below links to the phase 3 studies: in HIV/HCV coinfected, in cirrhotic patients and patients with post-liver transplant, and patients with genotype 3).
These drugs will be approved for genotype 1. Sofosbuvir+Ribavirin and Sofosbuvir+Peg/Rbv are approved for genotypes 2/3 - Dec 6, 2013 - U.S. Food and Drug Administration Approves Gilead's Sovaldi(TM) (Sofosbuvir) for the Treatment of Chronic Hepatitis C....http://www.natap.org/2013/HCV/120613_02.htm
IDSA: ABT-450/R/OMBITASVIR AND DASABUVIR WITH RIBAVIRIN ACHIEVES HIGH SUSTAINED VIROLOGIC RESPONSE RATES REGARDLESS OF BASELINE CHARACTERISTICS: POOLED ANALYSES OF THE SAPPHIRE-I AND SAPPHIRE-II STUDIES - (10/15/14)
IDSA: Safety of ABT-450/r/Ombitasvir + Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Patients, by Baseline Demographics - (10/15/14)
IDSA: Ledipasvir/Sofosbuvir is Safe and Effective as a Single-Tablet-Regimen for Treatment of Patients with Genotype 1 Chronic Hepatitis C Virus, Including those with Compensated Cirrhosis - (10/15/14)
FDA Sofosbuvir/ledipasvir Label/Package Insert & Patient Information HARVONI¨ Two PDFs - (10/11/14)
"-----------------------------INDICATIONS AND USAGE----------------------
HARVONI is a fixed-dose combination of ledipasvir, a hepatitis C virus (HCV) NS5A inhibitor, and sofosbuvir, an HCV nucleotide analog NS5B polymerase inhibitor, and is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection in adults (1)"
------------------------DOSAGE AND ADMINISTRATION----------------------
· Recommended dosage: One tablet (90 mg of ledipasvir and 400 mg of sofosbuvir) taken orally once daily with or without food (2.1)
· Recommended treatment duration (2.1):
· Treatment-naïve with or without cirrhosis: 12 weeks
· Treatment-experienced without cirrhosis: 12 weeks
· Treatment-experienced with cirrhosis: 24 weeks
· A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease (2.2)
Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection 12, 24 weeks GT1/2/3, FDA Approvals Oct 10 thru Dec This Fall - (10/02/14)
Janssen Submits Supplemental New Drug Application to U.S. FDA for OLYSIOª (Simeprevir) for Once-Daily Use in Combination with Sofosbuvir for 12 Weeks for the Treatment of Adult Patients with Genotype 1 Chronic Hepatitis C - (05/08/14)
EASL: Once-daily simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype-1 prior null responders with METAVIR F0-2: COSMOS study subgroup analysis - (04/14/14)
EASL: Simeprevir plus sofosbuvir with/without ribavirin in HCV genotype-1 prior null-responder / treatment-naïve patients (COSMOS study): primary endpoint (SVR12) results in patients with METAVIR F3-4 (Cohort 2) - (04/14/14)
Janssen Initiates Phase 3 OPTIMIST Trials of Once-Daily Simeprevir in Combination with Once-Daily Sofosbuvir for the Treatment of Genotype 1 Chronic Hepatitis C - (04/03/14)
Virology analyses of simeprevir in Phase 2b and 3 studies - (04/17/14)
Deep sequencing analyses of minority baseline polymorphisms and persistence of emerging mutations in HCV genotype 1-infected patients treated with simeprevir - (04/17/14)
Bristol-Myers Squibb Statement about Asunaprevir in the U.S. - (10/08/14)
Bristol-Myers Squibb Statement about Asunaprevir in the U.S.
Tuesday, October 7, 2014 8:30 am EDT
PRINCETON, N.J.--(BUSINESS WIRE)--Given the rapidly evolving hepatitis C (HCV) treatment landscape in the U.S., Bristol-Myers Squibb (NYSE:BMY) has decided that it will not pursue U.S. Food and Drug Administration (FDA) approval of the dual regimen of daclatasvir and asunaprevir for the treatment of HCV genotype 1b patients in the United States and has therefore withdrawn its new drug application (NDA) for asunaprevir, an NS3/4A protease inhibitor. The company will continue to pursue FDA approval of daclatasvir, a potent, pan-genotypic NS5A complex inhibitor (in vitro), which is currently being investigated globally in multiple treatment regimens for HCV patients with high unmet need.
Bristol-Myers Squibb's HCV strategy has always been to focus on the unique unmet medical need of each local market. For example, in Japan we were pleased to receive regulatory approval for the dual regimen of daclatasvir and asunaprevir in July, bringing Japanese patients with HCV the first all-oral, interferon- and ribavirin-free treatment regimen.
The dual regimen was developed to meet the distinct need of the Japanese patient population, and we believe this treatment has the potential to play a major role in curing HCV patients in Japan, as well as in other markets where the HCV patient population is similar to Japan. In the EU, daclatasvir was recently approved for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of HCV infection in adults. Similarly, we believe that daclatasvir-based regimens have the potential to fill continued unmet medical need in the U.S. and elsewhere in the world.
We plan to submit additional data for daclatasvir to the FDA from our ongoing clinical trial program focused on difficult-to-treat patients, including patients with HCV genotype 3, patients who are pre- and post-liver transplant, and patients co-infected with HIV. Next month at the annual meeting of The American Association for the Study of Liver Diseases (AASLD), we will present new data from several daclatasvir-based regimens. We look forward to bringing daclatasvir to patients in the U.S. and will continue to work closely with the FDA to advance our regulatory application, with the aim of bringing the investigational product to market as quickly as possible.
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