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New HCV Drug Achieves 100% Cure Rate Without Interferon
http://www.medscape.com/viewarticle/753186
"November 9, 2011 (San Francisco, California) — An interferon-free regimen for the treatment of infection with hepatitis C virus (HCV) might soon be available, according to data from the ELECTRON trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.
In ELECTRON — 1 of 2 phase 2 studies of the investigational compound PSI-7977 (Pharmasset) reported here — an interferon-free regimen of PSI-7977 plus ribavirin achieved a 100% sustained viral response (SVR) at 12 weeks in all study subjects. The second study, PROTON, was also reported here.
"PSI-7977 has the potential to dramatically change the treatment paradigm for HCV," said lead study investigator Edward Gane, MD, from Auckland City Hospital in New Zealand.
PSI-7977 is a uridine nucleotide analog polymerase inhibitor that is administered once daily with or without food. It has demonstrated robust activity in patients infected with HCV genotype 1 when used in combination with pegylated-interferon and ribavirin after a 12-week course.
Activity with this agent used as a monotherapy has also been reported.
"The aim of the ELECTRON trial was to determine the shortest duration of interferon, if any, required to achieve SVR when PSI-7977 plus ribavirin are administered for 12 weeks," Dr. Gane explained.
ELECTRON investigators recruited 40 patients who were randomized to 1 of 4 treatment groups: PSI-7977 400 mg plus ribavirin for 12 weeks plus interferon for 0, 4, 8, or 12 weeks.
Patients were treatment-naïve, noncirrhotic, infected with HCV genotype 2 or 3, and stratified by interleukin (IL)28B single-nucleotide polymorphisms (SNP) and HCV RNA levels. Mean age was 47 years and mean baseline HCV RNA was 6.49 log10 IU/mL, with 42.5% exhibiting the CC genotype at the IL28B SNP.
"We selected a genotype 2/3 population because this represents a population that would be more easily rescued with interferon in the event of virologic breakthrough," Dr. Gane explained.
Results after treatment initiation were dramatic. "All patients achieved a rapid virologic response, with over 80% being nondetectable at 2 weeks," reported Dr. Gane.
All patients had undetectable HCV at 3 weeks; furthermore, all patients achieved end-of-treatment response. No cases of treatment resistance were observed.
"Even following cessation of interferon, or with no interferon, there were no virologic breakthroughs on treatment." Also encouraging was the fact that all patients in the study experienced a rapid normalization of alanine aminotransferase.
There were no serious adverse events, and the mild to moderate events observed were attributed to either interferon or ribavirin. Significant improvements in safety and tolerability were seen in the interferon-free treatment group. No safety signals for PSI-7977 were observed, and there were no treatment-related discontinuations.
Results of the 12-week analysis prompted study investigators to add an exploratory treatment group of open-label PSI-7977 monotherapy for 12 weeks (n = 10). "The response was the same as with combination treatment with ribavirin," said Dr. Gane. Although this study is ongoing, 6 of 10 patients have achieved SVR at 4 weeks.
"These data clearly demonstrate that PSI-7977 exhibits high potency and has a high barrier to resistance," Dr. Gane said, noting that the drug is being advanced in phase 3 investigations in all HCV genotypes.
Too Good to be True?
Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, has doubts about PSI-7977. "If you use it with ribavirin and no interferon, you get a 100% SVR; if you use it alone, you get a 100% SVR."
Dr. Bernstein accepts the efficacy of PSI-7977 for the moment, but is concerned that ELECTRON isn't powered to say much about the tolerability or resistance profiles of the drug.
"What we've found with most of these [polymerase inhibitors] is that if you use them by themselves, you get resistance; if you don't, they can be very difficult to tolerate," said Dr. Bernstein. "There was a drug being investigated at Mount Sinai — a polymerase inhibitor, NM286 — and those patients got severe diarrhea and could not tolerate it. According to the ELECTRON study, everything was perfect — no gastrointestinal issues, no apparent adverse events of any kind, and it worked 100% of the time without interferon, or ribavirin.... If it's true, it will be great. The holy grail is to try to rid HCV treatment regimens of interferon."
Although sincerely impressed, Dr. Bernstein, who has seen many drugs come and go, suspects that as larger phase 3 trials of PSI-7977 are conducted, polymerase-associated adverse events, tolerability issues, and treatment resistance patterns will emerge."
"November 9, 2011 (San Francisco, California) — An interferon-free regimen for the treatment of infection with hepatitis C virus (HCV) might soon be available, according to data from the ELECTRON trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.
In ELECTRON — 1 of 2 phase 2 studies of the investigational compound PSI-7977 (Pharmasset) reported here — an interferon-free regimen of PSI-7977 plus ribavirin achieved a 100% sustained viral response (SVR) at 12 weeks in all study subjects. The second study, PROTON, was also reported here.
"PSI-7977 has the potential to dramatically change the treatment paradigm for HCV," said lead study investigator Edward Gane, MD, from Auckland City Hospital in New Zealand.
PSI-7977 is a uridine nucleotide analog polymerase inhibitor that is administered once daily with or without food. It has demonstrated robust activity in patients infected with HCV genotype 1 when used in combination with pegylated-interferon and ribavirin after a 12-week course.
Activity with this agent used as a monotherapy has also been reported.
"The aim of the ELECTRON trial was to determine the shortest duration of interferon, if any, required to achieve SVR when PSI-7977 plus ribavirin are administered for 12 weeks," Dr. Gane explained.
ELECTRON investigators recruited 40 patients who were randomized to 1 of 4 treatment groups: PSI-7977 400 mg plus ribavirin for 12 weeks plus interferon for 0, 4, 8, or 12 weeks.
Patients were treatment-naïve, noncirrhotic, infected with HCV genotype 2 or 3, and stratified by interleukin (IL)28B single-nucleotide polymorphisms (SNP) and HCV RNA levels. Mean age was 47 years and mean baseline HCV RNA was 6.49 log10 IU/mL, with 42.5% exhibiting the CC genotype at the IL28B SNP.
"We selected a genotype 2/3 population because this represents a population that would be more easily rescued with interferon in the event of virologic breakthrough," Dr. Gane explained.
Results after treatment initiation were dramatic. "All patients achieved a rapid virologic response, with over 80% being nondetectable at 2 weeks," reported Dr. Gane.
All patients had undetectable HCV at 3 weeks; furthermore, all patients achieved end-of-treatment response. No cases of treatment resistance were observed.
"Even following cessation of interferon, or with no interferon, there were no virologic breakthroughs on treatment." Also encouraging was the fact that all patients in the study experienced a rapid normalization of alanine aminotransferase.
There were no serious adverse events, and the mild to moderate events observed were attributed to either interferon or ribavirin. Significant improvements in safety and tolerability were seen in the interferon-free treatment group. No safety signals for PSI-7977 were observed, and there were no treatment-related discontinuations.
Results of the 12-week analysis prompted study investigators to add an exploratory treatment group of open-label PSI-7977 monotherapy for 12 weeks (n = 10). "The response was the same as with combination treatment with ribavirin," said Dr. Gane. Although this study is ongoing, 6 of 10 patients have achieved SVR at 4 weeks.
"These data clearly demonstrate that PSI-7977 exhibits high potency and has a high barrier to resistance," Dr. Gane said, noting that the drug is being advanced in phase 3 investigations in all HCV genotypes.
Too Good to be True?
Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, has doubts about PSI-7977. "If you use it with ribavirin and no interferon, you get a 100% SVR; if you use it alone, you get a 100% SVR."
Dr. Bernstein accepts the efficacy of PSI-7977 for the moment, but is concerned that ELECTRON isn't powered to say much about the tolerability or resistance profiles of the drug.
"What we've found with most of these [polymerase inhibitors] is that if you use them by themselves, you get resistance; if you don't, they can be very difficult to tolerate," said Dr. Bernstein. "There was a drug being investigated at Mount Sinai — a polymerase inhibitor, NM286 — and those patients got severe diarrhea and could not tolerate it. According to the ELECTRON study, everything was perfect — no gastrointestinal issues, no apparent adverse events of any kind, and it worked 100% of the time without interferon, or ribavirin.... If it's true, it will be great. The holy grail is to try to rid HCV treatment regimens of interferon."
Although sincerely impressed, Dr. Bernstein, who has seen many drugs come and go, suspects that as larger phase 3 trials of PSI-7977 are conducted, polymerase-associated adverse events, tolerability issues, and treatment resistance patterns will emerge."
Really nice to see good news for geno 2/3s... there's been so much hype about the PIs and focus on Geno 1s -- great to see progress being made on all fronts.
WOw Will!
Thank you that's insane I was thinking about doing that quantum trial
But was waiting for biopsy results First
I could have ended up with psi 938,With or without psi 7977
I am going with the Vic,peg + rib
By the way curious lady, 7977 maybe getting the positive attention right now but psi938 was the one that was fast tracked by the FDA in August
August 24, 2011
PSI-938 Receives Fast Track Designation from the FDA for the Treatment of Chronic Hepatitis C Infection
PRINCETON, N.J., Aug. 24, 2011 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) has received fast track designation from the U.S. Food and Drug Administration (FDA) for PSI-938 for the treatment of chronic hepatitis C virus (HCV) infection. PSI-938 is an oral guanosine nucleotide analog polymerase inhibitor of HCV.
In March 2011, Pharmasset presented data from the NUCLEAR study demonstrating that PSI-938 has potent antiviral activity and is generally safe and well tolerated, both as monotherapy and in combination with Pharmasset's lead nucleotide analog, PSI-7977. The NUCLEAR study was conducted in treatment naive subjects with genotype 1 HCV who were treated for 14 days with either PSI-938 or a combination of PSI-938 and PSI-7977 with 92% achieving HCV RNA <15IU/mL, the limit of detection, in the combination arms. Pharmasset plans to initiate QUANTUM, an interferon-free combination trial with PSI-938 and PSI-7977 in the third quarter of 2011.
Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious and life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. PSI-938 was granted the fast track designation primarily due to the need for HCV treatments with improved tolerability, safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in four Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
richard.***@****
Office: +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
News Provided by Acquire Media
Thank you that's insane I was thinking about doing that quantum trial
But was waiting for biopsy results First
I could have ended up with psi 938,With or without psi 7977
I am going with the Vic,peg + rib
By the way curious lady, 7977 maybe getting the positive attention right now but psi938 was the one that was fast tracked by the FDA in August
August 24, 2011
PSI-938 Receives Fast Track Designation from the FDA for the Treatment of Chronic Hepatitis C Infection
PRINCETON, N.J., Aug. 24, 2011 /PRNewswire/ -- Pharmasset, Inc. (Nasdaq: VRUS) has received fast track designation from the U.S. Food and Drug Administration (FDA) for PSI-938 for the treatment of chronic hepatitis C virus (HCV) infection. PSI-938 is an oral guanosine nucleotide analog polymerase inhibitor of HCV.
In March 2011, Pharmasset presented data from the NUCLEAR study demonstrating that PSI-938 has potent antiviral activity and is generally safe and well tolerated, both as monotherapy and in combination with Pharmasset's lead nucleotide analog, PSI-7977. The NUCLEAR study was conducted in treatment naive subjects with genotype 1 HCV who were treated for 14 days with either PSI-938 or a combination of PSI-938 and PSI-7977 with 92% achieving HCV RNA <15IU/mL, the limit of detection, in the combination arms. Pharmasset plans to initiate QUANTUM, an interferon-free combination trial with PSI-938 and PSI-7977 in the third quarter of 2011.
Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious and life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. PSI-938 was granted the fast track designation primarily due to the need for HCV treatments with improved tolerability, safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in four Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in three Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.
Contact
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
richard.***@****
Office: +1 (609) 613-4181
Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
News Provided by Acquire Media
Thanks for posting. I was wondering about PSI 938. There was not much news about it except for early efficacy test results. In the commercial world no news isn't usually good news.
PSI 7977 still looks brilliant though.
PSI 7977 still looks brilliant though.
Promising news!! Thanks for posting this. This does sound like the Holy Grail for Hep C, so let us pray that the drug companies continue to do all their homework, to give us the safest, most tolerable, most effective route to SVR.
http://www.aidsmeds.com/articles/psi7977_hcv_genotype1_1667_21428.shtml .
The less benign study you posted still contains ribavirin and the dreaded interferon you have constantly protested agaist using. What is exactly less benign about it. SX of the protease inhibitors are not a given in all patients, I never got the incivek rash, have not been anemic or really had any adverse events, nausea was my worst side effect. I am in week 17 and doing fine so to say all will get severe side effects is not a valid statement.
The less benign study you posted still contains ribavirin and the dreaded interferon you have constantly protested agaist using. What is exactly less benign about it. SX of the protease inhibitors are not a given in all patients, I never got the incivek rash, have not been anemic or really had any adverse events, nausea was my worst side effect. I am in week 17 and doing fine so to say all will get severe side effects is not a valid statement.
I am not referring to people who are already in treatment will but to those considering it. There are many who adamently will not treat as long as drugs with severe side effects are their only option.
Anyway, for those who dont want to give up their interferon based treatment, at the very least we ought to be looking at a much more benign triple:
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Give it up and currently treat with what? Yes..they are looking at possibly more benign therapies...however as been stated many times,this is going to take time and with many glitches along the way...
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Give it up and currently treat with what? Yes..they are looking at possibly more benign therapies...however as been stated many times,this is going to take time and with many glitches along the way...
Let us remember that PSI 938 which is the cause of the news story is not Pharmasset's premier drug. They also had another drug which was used in a French Roche study and wasnt all that effective I don't think. The premier drug is PSI 7977. Let us also remember that the "excellent drugs" available now have substantial side effects that can be debilitating. Those problems are what is pushing the industry to continue to search and not to settle.
Anyway, for those who dont want to give up their interferon based treatment, at the very least we ought to be looking at a much more benign triple:
http://www.aidsmeds.com/articles/psi7977_hcv_genotype1_1667_21428.shtml
Anyway, for those who dont want to give up their interferon based treatment, at the very least we ought to be looking at a much more benign triple:
http://www.aidsmeds.com/articles/psi7977_hcv_genotype1_1667_21428.shtml
This is why we must wait patiently ....it takes many years and often with glitches along the way.
------------------------------------------------------------------------------------------------
Meant to say: This is why we must wait patiently,before we jump to conclusions on newer drugs.. not necessarily that we must wait patiently to treat ...there are excellent drug we can choose now
------------------------------------------------------------------------------------------------
Meant to say: This is why we must wait patiently,before we jump to conclusions on newer drugs.. not necessarily that we must wait patiently to treat ...there are excellent drug we can choose now
They were actually talking about Hep C this morning on Squawk on the Street on CNBC. I couldn't believe it. VRUS and GILD were all over the Dow Jones news ticker
This is why we must wait patiently ....it takes many years and often with glitches along the way.
Will
Pharmasset Halts Hepatitis C Drug In Mid-Stage Trial
-Use of PSI-938 halted in clinical trial due to liver-related abnormalities
Studies of lead hepatitis C candidate, PSI-7977, continue
--Pharmasset says setback won't derail $11 billion sale to Gilead
By Peter Loftus
Of DOW JONES NEWSWIRES
Pharmasset Inc. (VRUS) discontinued use of an experimental hepatitis C drug in a clinical trial because of safety concerns, but the drug maker said the setback wouldn't derail its planned sale to Gilead Sciences Inc. (GILD) for nearly $11 billion.
The company discontinued use of a drug code-named PSI-938 in a mid-stage study of people with hepatitis C infection, citing "laboratory abnormalities associated with liver function." However, it will continue testing its lead hepatitis C drug candidate, PSI-7977, which was the primary selling point behind the Gilead deal and wasn't associated with the abnormalities
Will
Pharmasset Halts Hepatitis C Drug In Mid-Stage Trial
-Use of PSI-938 halted in clinical trial due to liver-related abnormalities
Studies of lead hepatitis C candidate, PSI-7977, continue
--Pharmasset says setback won't derail $11 billion sale to Gilead
By Peter Loftus
Of DOW JONES NEWSWIRES
Pharmasset Inc. (VRUS) discontinued use of an experimental hepatitis C drug in a clinical trial because of safety concerns, but the drug maker said the setback wouldn't derail its planned sale to Gilead Sciences Inc. (GILD) for nearly $11 billion.
The company discontinued use of a drug code-named PSI-938 in a mid-stage study of people with hepatitis C infection, citing "laboratory abnormalities associated with liver function." However, it will continue testing its lead hepatitis C drug candidate, PSI-7977, which was the primary selling point behind the Gilead deal and wasn't associated with the abnormalities
Most of us don't fit in that category but the efficacy with interferon for geno 1 is still extremely high and the potential to use it in combo with other direct anti virals for most of us who are tougher to treat is great.
-Dave
-Dave
Yes I dont fit into that category but it would be wonderful to get rid of interferon.
Here's the geno 1 info with interferon:
http://www.hepctrust.org.uk/Treatment/Potential+New+Drugs/Drugs+that+target+the+virus/Pharmasset+PSI+7977
http://www.hepctrust.org.uk/Treatment/Potential+New+Drugs/Drugs+that+target+the+virus/Pharmasset+PSI+7977
Great news on this drug but important to remember that this was the easiest to treat population. They may have even been able to SVR with colloidal silver alone (just kidding of course)
"Patients were treatment-naïve, noncirrhotic, infected with HCV genotype 2 or 3, and stratified by interleukin (IL)28B single-nucleotide polymorphisms (SNP) and HCV RNA levels. Mean age was 47 years and mean baseline HCV RNA was 6.49 log10 IU/mL, with 42.5% exhibiting the CC genotype at the IL28B SNP"
"Patients were treatment-naïve, noncirrhotic, infected with HCV genotype 2 or 3, and stratified by interleukin (IL)28B single-nucleotide polymorphisms (SNP) and HCV RNA levels. Mean age was 47 years and mean baseline HCV RNA was 6.49 log10 IU/mL, with 42.5% exhibiting the CC genotype at the IL28B SNP"
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