Treatment News : Twelve Weeks Interferon-Free PSI-7977 Regimen Cures 100 Percent Hep C Genotype 2/3

Twelve Weeks Interferon-Free PSI-7977 Regimen Cures 100 Percent Hep C Genotype 2/3

A twelve-week course of Pharmasset’s once-daily experimental nucleotide analog PSI-7977, combined with ribavirin, cured 10 of 10 people living with genotype 2/3 hepatitis C virus (HCV) who used the regimen—without pegylated interferon—in a Phase II clinical trial. The highly encouraging results were reported Sunday, November 6, at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.

Compared with the three other groups included in the study, which involved taking PSI-7977 plus ribavirin with either four, eight or 12 weeks of pegylated interferon, significant improvements in safety and tolerability were also documented among those using PSI-7977 plus ribavirin alone, according to Edward Gane, MD, of the Auckland City Hospital in Auckland, New Zealand, and his ELECTRON study colleagues.

Results from early studies of PSI-7977 have been promising. In the PROTON study, PSI-7977 combined with pegylated interferon plus ribavirin resulted in sustained virologic responses (SVRs)—viral cures—in 96 percent of study volunteers with HCV genotype 2/3 and 91 percent of those with HCV genotype 1 (the most common yet hardest-to-treat form of the virus in the United States).

ELECTRON, initiated in December 2010, was conducted to determine the shortest duration of pegylated interferon—if any—required to achieve SVRs when PSI-7977 plus ribavirin are given for 12 weeks. HCV genotype 2/3 patients were initially selected for this unorthodox study—pegylated interferon has long been a mainstay agent in hepatitis C drug regimens—given pegylated interferon and ribavirin tend to be much more effective for individuals with genotype 2/3 virus and could be called upon in the event of poor responses to PSI-7977/ribavirin in the study.

No “rescue” therapy proved necessary. At virtually all study time points—weeks 4, 8 and 12 during therapy and weeks 4, 8, 12 and 24 following the completion of treatment—100 percent of the patients in each group maintained undetectable HCV viral loads. Eleven patients received PSI-7977/ribavirin plus 12 weeks of pegylated interferon, 10 received PSI-7977/ribavirin plus eight weeks of pegylated interferon, nine received PSI-7977/ribavirin plus pegylated interferon and ten received PSI-7977/ribavirin without pegylated interferon.

Gane noted that HCV viral load suppression was rapid in all four treatment groups—virtually everyone had HCV below the level of detection within three weeks of beginning treatment.

At least one side effect—including headache, fatigue, depression, insomnia, anxiety, irritability, muscle soreness and upper respiratory tract infections—was more likely to be documented in those in the 12-week pegylated interferon group (72 percent), compared with those who didn’t receive any pegylated interferon (40 percent).

Similarly, whereas moderate-to-severe drops in neutrophils—a type of white blood cell—was documented in roughly 70 percent of those in the 12-week pegylated interferon group, no volunteers in the interferon-free PSI-7977/ribavirin group experienced this toxicity. Interferon-free PSI-7977 plus ribavirin also had much less of an impact on hemoglobin levels, a marker of anemia.

Also encouraging, all patients in the study experienced a rapid normalization of ALT, a key liver enzyme. Among those in the interferon-free treatment group, normal ALT levels were documented in all patients by the end of the third week of treatment.

In summary, Gane noted, “PSI-7977 [400 milligrams once daily] remains very well tolerated with no attributable safety signal, no treatment discontinuations and no treatment emergency laboratory abnormalities.” As for potency, he concluded that PSI-7977/ribavirin “elicited rapid suppression” of HCV viral load in study volunteers with HCV genotype 2 or 3 and that all 40 patients in the study achieved an SVR, regardless of whether or not interferon was used. Additionally, not a single case of drug-resistant virus emerged during the study.

Further results from ELECTRON are expected. The study has been amended, adding several new treatment groups. One group is exploring PSI-7977 used as monotherapy—without pegylated interferon or ribavirin—to treat genotype 2/3 infection. Preliminary data reported by Gane's team suggest that four patients in this group have maintained undetectable HCV levels four weeks after discontinuing treatment.

Another group is studying PSI-7977 in combination with pegylated interferon plus ribavirin, again in genotype 2/3 patients, but for only eight weeks.

Three additional groups are now enrolling patients. One is studying 12 weeks of PSI-7977 plus ribavirin, without interferon, in HCV genotype 2/3 patients who weren't able to clear the virus with 24 weeks of previous pegylated interferon/ribavirin therapy. A second is evaluating PSI-7977 plus ribavirin in HCV genotype 1 patients beginning therapy for the first time. The third group consists of individuals with HCV genotype 1 null responders (patients who responded very poorly to prior pegylated interferon/ribavirin treatment); they will receive PSI-7977/ribavirin for a total of 12 weeks.

Pharmasset recently announced its Phase III clinical trial program. Two studies—FISSION and POSITRON—will further explore the safety and efficacy of PSI-7977 plus ribavirin, but without pegylated interferon, in approximately 725 people with genotype 2/3 HCV infection. A third study will explore PSI-7977 in HCV genotype 1 patients, with the design of the study determined by the ongoing ELECTRON clinical trial and another study still under way.

varun, delhi, 2012-05-10 08:17:14
its such a usefull info regarding genotype 2/3. thank u.

ahmed qasem, Egypt, 2012-04-19 18:14:02
im assistant lecture of gastroentrology and hepatology alazhar univeristy i want to know more about psi7977 so i have mor patient complaining of chronic hepatites c

Muhammad Ejaz, Lahore, 2012-04-05 09:50:56
I am 30 years old (80 KG weight) and have HCV, Genotype 3a. I got treated with interferon/ribavirin last year and cleared the virus but, after 7 months of treatment, HCV is back again.

I am much interested to be part of clinical trial where they are studying ( with 12 weeks of PSI-7977 plus ribavirin, without interferon) in HCV genotype 2/3 patients who weren't able to clear the virus within 24 weeks of previous pegylated interferon/ribavirin therapy.

Tim Horn, New York, NY, 2012-04-02 13:17:46
Ehsan, U.S. approval of 7977, now called GS-7977, is expected sometime during the first half of 2014. If you go to clinicaltrials.gov and search for 7077 + POSITRON, you will see that a study group is still enrolling volunteers with genotype 3 HCV infection. Best of luck!

ehsan, Lahore-Pakistan, 2012-04-02 11:25:50
I have HCV Genotype 3a and have never been treated. I am keenly interested for clinical trials of PSI-7977. Please let me have your response, if not, please advise when should we expect this medicine in clinics? Regards

Remy, Borger N.L., 2012-03-08 11:52:11
I heard last monday from my internist about PSI 7977. This is very promising if it reaches us in time!!!2013 in U.S.A.! when in Europe? 2099? I have type C1a and been since 33 years infected, liver nearly gone, will I be allowed to live before some infestors have become stinking rich of the alternatif being transplantation and making the rest of live very miserable. Can you help? my 8 years old son would really like that. Are there tests here to participate? heal an old infection! Interresting!!

Hopelife, , 2012-03-01 16:44:31
This is amazing news. I tried interferon ribavrin for 24 weeks but non response of genotype 3. I am intrested for clinical trial. please respond me back if I can be a candidate for PSI-7977.

Brian, Boston, MA, 2012-02-14 11:37:49
This is amazing news! I hear from my doc that it is likely this will be approved in late 2013 by FDA. They will not trail patients co-infected and so its a bummer to wait but I cleared with interferon and Ribavarin in 4 weeks but at 5 weeks got an infection (site injection!) and had no white cells or RBC due to interferon so its not tolerable and it came back to my chagrin in spite of being cleared you needed another 4 wks-but no go. This is a god send as interferon is toxic-praying ASAP ready!

Jamie, Dana point, 2011-12-19 12:02:32
Is it possible to be treated with your therapy in the U.S. Is this only a finding from Australia that we don't have available yet.?? I'm very interested in trying to be accepted for a clinical trial treatment of Genotype 1.

LARRY COHN, Seattle, 2011-11-15 11:08:46
I've had hep C for nearly 20 years. Unfortunatly, I'm genome 1. I saw my doctor Nov 9th, and he was very excited about PSI-7977. I've been seeing him about 4 years, and trying to get up the nerve for the interferon, ribvarin treatment. He kept recommending I wait for some of the new drugs in the pipeline (I'm sure he ment the protease inhiberts). Anyway, I know how small the sample was, and many miracle cures get shot down. I'll keep tracking all the studies, and am much more optimistic then even a week ago. I can't thank u enough,,,,,LARRY

Jeremy, charlotte,nc, 2011-11-07 22:21:09
That sounds great after reading and finding out that new drugs are being used but sadly for genotype 1 non responders I was told acouple weeks ago from a hepc doc . Now I am a non response genotype 2 and would really like to try this can u tell me where to go ?shud I ask the doc I seen about this since its new I would figure he would call but . thx for posting this! Good news ...