By Todd Neale, Senior Staff Writer, MedPage Today
Published: April 19, 2012
The investigational drug GS-7977 performed well against hepatitis C virus (HCV) in treatment-naive patients, with or without contributions from pegylated interferon and ribavirin, several studies showed.
In a phase II study, GS-7977 (a nucleotide NS5B inhibitor) combined with daclatasvir (a novel NS5B inhibitor) resulted in rapid and sustained viral responses in patients infected with HCV genotypes 1, 2, or 3, Mark Sulkowski, MD, of Johns Hopkins University, reported at the European Association for the Study of the Liver meeting in Barcelona.
And in another phase II study, presented by Kris Kowdley, MD, of Virginia Mason Medical Center in Seattle, GS-7977 combined with pegylated interferon and ribavirin showed similar efficacy in patients with HCV genotype 1, the hardest-to-treat strain.
GS-7977 and daclatasvir are two of several new drugs being developed that directly target HCV, with the aim of moving away from the use of pegylated interferon and ribavirin, which boost the immune system to battle the virus but come with multiple side effects. Those include flu-like symptoms, depression, neutropenia, thrombocytopenia, and anemia.
In the study presented by Sulkowski, treatment-naive patients with HCV genotype 1, 2, or 3 were randomized to one of three arms:
- Daily GS-7977 400 mg for 7 days followed by GS-7977 plus daily daclatasvir 60 mg for 23 weeks
- Daily GS-7977 and daclatasvir for 24 weeks
- Daily GS-7977 and daclatasvir plus ribavirin for 24 weeks
The 44 patients with genotype 1 were randomized separately from the 44 with genotypes 2 and 3.
By week four of treatment, all patients had a sustained viral response. That figure was no lower than 86% in any group at the end of treatment and at four weeks after the end of treatment.
Ribavirin did not accentuate the virologic response.
The treatment was relatively well tolerated, and the most frequent adverse events were fatigue, headache, and nausea. Grade 3/4 laboratory abnormalities included elevated cholesterol in one patient, elevated glucose in two, low hemoglobin in six, lymphopenia in one, and low phosphorus in two.
The study presented by Kowdley -- the ATOMIC study -- included 316 patients with HCV genotype 1, 11 with genotype 4 and five with genotype 6. They were noncirrhotic, were treatment-naive, and had an HCV RNA of at least 50,000 IU/mL. There were three treatment arms:
- Daily GS-7977 400 mg plus pegylated interferon (180 µg weekly injection) and ribavirin (500 mg twice daily) for 12 weeks
- Daily GS-7977 400 mg plus pegylated interferon and ribavirin for 24 weeks
- Daily GS-7977 400 mg plus pegylated interferon and ribavirin for 12 weeks, with re-randomization at week 12 to GS-7977 alone or GS-7977 plus ribavirin for the rest of the study
By week two of treatment, 78% had HCV RNA below the level of detection, and 97% achieved a rapid viral response (HCV RNA undetectable after 4 weeks of treatment).
At 4 weeks after treatment ended, 92% of patients had a sustained viral response.
Among the patients randomized to the 12-week treatment arm, 90% achieved a sustained virologic response 12 weeks after treatment ended.
As in the other study, GS-7977 was generally well tolerated with adverse events consistent with the safety profile of interferon and ribavirin. Side effects included fatigue (54%), nausea (29%), headache (29%), chills (19%), and insomnia (19%).
Also See:
- EASL 2012: All-Oral Combination of Investigational Hepatitis C (HCV) Compounds Daclatasvir and GS-7977 Achieved Sustained Virologic Response (SVR4) in 100% of Genotype 1 and 91% of Genotype 2 and 3 Treatment-Naïve Patients in Phase II Study
- EASL 2012: Gilead Announces Sustained Virologic Response Data for 12-Week Regimen of GS-7977 Plus Pegylated Interferon and Ribavirin in Genotype 1 Hepatitis C Patients
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