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Daclatasvir and GS-7977

July 2012

Daclatasvir was the first oral HCV NS5A inhibitor to be developed. GS-7977 is a nuke with activity against NS5B. Both drugs have powerful anti-HCV activity when used separately. In study AI444-040, researchers in the U.S. studied different combinations of both drugs in a randomized clinical trial with HCV-positive people infected with the following genotypes:

  • genotype 1a, 1b, 2, and 3

Researchers recruited participants and assigned them to the following six groups:

Group A

  • 15 participants with genotypes 1a and 1b: all received GS-7977 monotherapy for seven days after which daclatasvir was added; dual therapy continued for 23 weeks

Group B

  • 16 participants with genotypes 2 and 3: all received GS-7977 monotherapy for seven days after which daclatasvir 60 mg once daily was added; dual therapy continued for 23 weeks
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Group C

  • 14 participants with genotypes 1a and 1b: all received immediate dual therapy with daclatasvir and GS-7977, both for 24 weeks

Group D

  • 14 participants with genotypes 2 and 3: all received immediate dual therapy with daclatasvir and GS-7977, both for 24 weeks

Group E

  • 15 participants with genotypes 1a and 1b: all received triple therapy with daclatasvir, GS-7977 and ribavirin (dosed between 1,000 and 1,200 mg/day), all for 24 weeks

Group F

  • 14 participants with genotypes 2 and 3: all received triple therapy with daclatasvir, GS-7977 and ribavirin at 800 mg/day, all for 24 weeks

All participants were monitored for an additional 24 weeks once they stopped experimental therapy.

The average profile of participants upon entering the study was as follows:

  • age -- 53 years
  • 50% men, 50% women
  • HCV viral load -- 4 million IU/ml


Results

The decline in HCV levels was faster among participants who received combination therapy immediately rather than delaying combination therapy. Viral suppression was similar in groups C, D, E and F.

Adding ribavirin did not accelerate the decline of HCV viral load.

After four weeks of experimental therapy, 100% of genotype 1 participants had undetectable levels of HCV. The equivalent figure for genotype 2 and3 participants was 91%.

Two participants stopped returning to the study clinic for unknown reason(s). Their last blood samples at weeks 12 and 24 respectively were undetectable.

One participant had his HCV levels rise after first suppressing them.

Another participant (in group B) had his HCV levels rise but doctors enhanced his therapy with interferon + ribavirin and his viral load returned to suppressed levels.


Safety

No deaths occurred.

Two participants left the study because of adverse events: one case of stroke (group C) and one case of fibromyalgia (group F). Researchers considered both incidents to be unrelated to the study.

Serious adverse events occurred in 10 patients, but only three cases were judged to be related to the study medicines and all occurred when patients accidentally took extra doses of daclastavir or GS-7977.

Adverse events in the study that were not related to the experimental treatments were as follows:

  • anxiety -- 2 participants
  • fracture -- 1 participant
  • lung pain -- 1 participant
  • intestinal inflammation -- 1 participant
  • kidney failure -- 1 participant

No cases of severely elevated liver enzymes occurred.

The most common laboratory abnormality was anemia and this occurred in participants who received ribavirin.

In summary, the all-oral regimen of two new drugs without ribavirin cured 100% of genotype 1 participants and at least 90% of genotype 2 and 3 participants.

These very promising findings require confirmation in a larger study.


Reference

Sulkowski M, Gardiner D, Lawitz E, et al. Potent viral suppression with the all oral combination of daclatasvir (NS5A inhibitor) and GS-7977 (nucleotide NS5B inhibitor), +/- ribavirin, in treatment-naive patients with chronic HCV genotype 1,2 or 3. In: Program and abstracts of the 47th annual meeting of the European Association for the Study of the Liver, 18-22 April 2012, Barcelona, Spain.




This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.
 

Reader Comments:

Comment by: Rogerio R. (Curitiba Paraná Brasil) Fri., Sep. 14, 2012 at 5:42 pm EDT
I really hope that this new drug can achieve cure of this disgusting disease. I will keep in touch observing the final results of this trial. T am MD (urologist) and I was infected during a operative procedure, in 1982. Since then I have done no treatment and have mild liver fibrosis.
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Comment by: Michael J E. (Costa Mesa, CA) Fri., Aug. 17, 2012 at 9:06 am EDT
Very encouraging news about the continuing battle against this devastating disease. I prayer the more studies are done and that this drug can get to market as soon as possible. We want to fast-track the drugs, but we also have to know what we're dealing with. God bless all those with HIV / AIDS / HEP C! And to all those doctors, nurses and researchers who do all this hard labor, sometimes in the middle of the night because of the fear still associated with having these chronic conditions. These are the front line warriors! Give them all a standing ovation! Amen!
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Comment by: Margaret D. (San Antonio, TX) Sat., Aug. 4, 2012 at 9:57 pm EDT
Sign the petition at Change.org OR we will never get this life-saving drug combination. What kind of world is this where a company such as Gilead Sciences is "allowed" to withhold this from the millions of people who are suffering and dying with Hepatitis C? You found the CURE and now you aren't going to let us have it??? Would a company get away with this if it were the CURE FOR CANCER? We do NOT want the ravaging and debilitating side effects of Ribavirin OR interferon! Sign the petition at http://www.change.org/petitions/gilead-sciences-please-collaborate-with-bristol-myers-for-the-cure-for-hepatitis-c-now and let Gilead Sciences KNOW that the WORLD IS WATCHING! Gilead Sciences put patients FIRST and the PROFITS WILL FOLLOW. Only 3% of the population now treats. If this drug-combination was available, perhaps as many as 80 to 95% would treat! You could re-coup the $11 billion you spent for this CURE in no time! HCV now kills more people than AIDS...and you can CURE this disease! Have you NO SHAME Gilead Sciences?

http://www.change.org/petitions/gilead-sciences-please-collaborate-with-bristol-myers-for-the-cure-for-hepatitis-c-now

Margaret Dudley
HCV Sufferer & Advocate for THE CURE
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