Ledipasvir (GS-5885), Extra Drug Hikes HCV Regimen's Efficacy


Extra Drug Hikes HCV Regimen's Efficacy

By Michael Smith, North American Correspondent, MedPage Today
Published: March 04, 2013

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

ATLANTA – Adding an extra drug to a promising hepatitis C (HCV) regimen increased its efficacy – especially in patients who had failed previous standard therapy, a researcher said here.

The addition of the third drug meant that all patients, regardless of previous treatment, were free of the virus 12 weeks after the end of therapy, according to Edward Gane, MD, of Auckland City Hospital in Auckland, New Zealand.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Note that this small trial of three antiviral medications demonstrated a 100% sustained virologic response rate at 12 weeks in patients with Hepatitis C, regardless of prior treatment outcome.
  • Be aware that the study excluded patients with existing cirrhosis.

    The combination did not give rise to any new safety or tolerability issues, Gane told reporters in a press conference here at the Conference on Retroviruses and Opportunistic Infections.

    The new drug is ledipasvir, previously known as GS-5885, which blocks the action of the viral nonstructural protein 5A. Gane and colleagues added it to the nucleotide analogue sofosbuvir (GS-7977) and ribavirin, long a part of standard therapy.

    An advantage of the combination is that it avoids pegylated interferon, long part of the standard HCV therapy but regarded as both hard to tolerate and dangerous to use. Another benefit: All three drugs in the combination are taken orally, while interferon is given by injection.

    The earlier results showed that 84% of patients who had never been treated for chronic HCV infection were free of the virus 12 weeks after the end of 12 weeks of therapy – the so-called 12-week sustained virologic response (SVR12).

    But, Gane noted, patients who had not had a successful response to standard therapy with interferon and ribavirin – so-called null responders -- did much worse, with only 10% reaching an SVR12.

    The researchers had two choices to improve efficacy, he told reporters – increase the length of treatment or add an extra medication. They opted for the second choice, enrolling 25 treatment-naïve patients and 10 null-responders, all with the relatively hard-to-treat genotype 1 of the virus.

    As in the previous trial, response was quick, with all but one patient having no detectable virus after 4 weeks of therapy and all patients undetectable at the end of treatment.

    All patients in both groups also achieved an SVR12, Gane reported.

    There were two serious adverse events, both among the treatment-naïve group, but they were considered not related to treatment. One of the patients, with a diverticular perforation, stopped therapy after 8 weeks, but later was shown to be free of virus 24 weeks after the end of treatment.

    Gane commented that future study will use a co-formulated version of sofosbuvir and ledipasvir and will evaluate patients with cirrhosis who were excluded from this trial or had shorter durations of treatment. It will also look at the possibility of eliminating ribavirin.

    Although the results overcome the surprising findings of the earlier trial, they were achieved in a relatively easy-to-treat population, commented Juergen Rockstroh, MD, of the University of Bonn, who was not involved in the study but who moderated the session at which it was presented.

    "They got a 100% cure rate, but they had no cirrhotics," Rockstroh told MedPage Today. "They didn't give us an answer in a really difficult-to-treat population."

    Taken with other research presented here, the findings suggests that a one-size-fits-all approach may not be valid for future HCV treatment, he said – those who have advanced liver disease or have previously failed therapy may need more intensive therapy than other patients.

    The regimen has the advantage, however, that it does not include interferon, commented David Thomas, MD, of Johns Hopkins University, who was not involved in the study but who moderated a press conference at which some details were presented.

    "Interferon has been the workhorse," he told reporters, "but now we are moving into automobiles."

  • http://www.medpagetoday.com/MeetingCoverage/CROI/37654

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