CROI 2012: Interferon-Free Hepatitis C Tx Hits Snag

By Michael Smith, North American Correspondent, MedPage Today

Published: March 07, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

SEATTLE -- Results in a hard-to-treat patient group have clouded the future of a closely watched agent that acts directly against hepatitis C.

Action Points

• 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.
• Despite impressive results during treatment of hepatitis C virus with the investigational compound PSI-7977, all but one of the patients relapsed almost immediately after treatment stopped.
• The drug was being given in combination with ribavirin, one of the standard hepatitis C drugs, but without the other standby, pegylated interferon.

Despite impressive results during treatment with the compound dubbed PSI-7977, all but one of the patients relapsed almost immediately after treatment stopped, according to Edward Gane, MD, of Auckland City Hospital in Auckland, New Zealand.

The drug was being given in combination with ribavirin, one of the standard hepatitis C drugs, but without the other standby, pegylated interferon, Gane told reporters at the annual Conference on Retroviruses and Opportunistic Infections.

Among researchers and clinicians, there has been intense interest in the compound, a nucleotide analog, because of the potential to eliminate interferon, whose side effects make treatment difficult for many patients.

"The holy grail is treating people without interferon," commented David Thomas, MD, of Johns Hopkins University in Baltimore, who was not part of the study but who chaired a press conference at which details were presented.

But he told MedPage Today the results being presented here are disappointing, especially since the drug appeared to be remarkably effective in patients with relatively easy-to-treat disease.

In earlier results from the phase II ELECTRON study, patients with genotypes 2 and 3 of the virus were completely cured after just 12 weeks of therapy with PSI-7977 combined with ribavirin, Gane noted.

But researchers were also testing the combination in 10 patients with genotype 1 hepatitis C who had previously not responded to standard therapy with ribavirin and interferon, and in 25 genotype 1 patients who had not yet been treated, Gane said.

The initial responses in both groups were similar to those seen in genotypes 2 and 3 -- a quick drop to undetectable levels of virus followed by complete suppression throughout the 12-week treatment period, Gane said.

But all but one of the so-called null responders relapsed, with hepatitis C levels rising sharply within days of stopping the drug, Gane reported. Data on the treatment-naïve patients is not complete yet and will be reported in the next few months, he added.

"It's still a drug we're excited about, but these data put some limits on its use," Thomas said.

"The drug was curing [patients with] genotypes 2 and 3 in 12 weeks with just ribavirin," he said, but that doesn't appear to be possible in the hardest-to-treat subgroup.

Now, he said, the researchers have to do "a lot of hard work" to figure how to overcome the obstacles.

Any new study in genotype 1 null responders will either be longer in duration, or will add another direct-acting agent, or both, Gane said. But the researchers and the drug's manufacturer haven't settled on what they'll do.

Gane said the researchers will offer the relapsed patients a rescue protocol with PSI-7977 and another medication, but, again, they haven't decided what that drug will be.

The study was supported by Giliad.

Gane reported financial links with Gilead, Janssen-Cilag, Novartis, Pharmasset, and Vertex.

Thomas reported financial links with Gilead and Merck.

Primary source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Gane E, et al "100% rapid virologic response for PSI-7977 + ribavirin in genotype 1 null responders (ELECTRON): early viral decline similar to that observed in genotype 1 and genotype 2/3 treatment-naïve patients" CROI 2012; Abstract 54LB.

Source

Also See: CROI 2012: PSI-7977/ribavirin combo achieved rapid response in HCV genotype-1