Nice scorecard from The Street's Adam Feuerstein on how the HCV drug development marketplace looks post-EASL. I think folks are a little to bullish on Pharmasset's all-oral combo. To the company's credit, no one has shown this sort of efficacy without the help of ribavirin and peg, but 14 days is long way from SVR. It will be interesting to see how this all sorts out.
Biotech Stock Mailbag: Hep C Stock Winners
Adam Feuerstein
04/08/11 - 07:00 AM EDT
BOSTON (TheStreet) -- Trying to make sense of the rapidly changing field of hepatitis C drug research kicks off this week's Biotech Stock Mailbag.
Evan R. emails, "It looks like Pharmasset(VRUS) was the big winner at the hepatitis C conference. What's your take on hepatitis C stocks now?"
I could easily devote this entire Mailbag to hepatitis C because so much of the data presented at the just-wrapped European Association for the Study of the Liver (EASL) meeting has the potential to radically improve the way hepatitis C is treated. It's never a great time to be a Hep C patient, obviously, but the prospect for better, faster and more well-tolerated cures coming relatively soon should be a real source of hope and optimism.
Investors have a tougher challenge trying to pick a winning stock or two (or three of four) from among the many that are racing to bring these new Hep C drugs to market.
Case in point: The buzz at this week's EASL meeting was about new, all-oral multi-drug combinations for Hep C treatment that won't likely be ready for approval or sale for four or five years. The Hep C treatment landscape is evolving quickly and investors are jumping so far ahead that the looming April/May advisory panels and approval decision dates for new drugs from Vertex Pharmaceuticals(VRTX) and Merck(MRK) seem like old news already.
It sounds incredibly weird to even conjure this thought, but from Wall Street's what-have-you-done-for-me-lately perspective, Vertex's telaprevir and Merck's boceprevir look a bit old in the tooth even before the two drugs are approved!
Pharmasset was the belle of the EASL ball after presenting early data (in a relatively small number of patients) demonstrating that two oral drugs -- PSI 7977 and PSI 938 -- could render the Hep C virus undetectable with no obvious signs of resistance or relapse. This still-experimental regimen is remarkable for the absence of interferon or ribavirin -- the former injected, the latter oral -- which make up the current standard of care for Hep C treatment.
A typical Hep C patient today is treated with interferon and ribavirin for one year, enduring side effects that include flu-like symptoms for a 40% to 50% chance of being cured.
By this spring or early summer, the addition of 12 weeks of treatment with Vertex's telaprevir to a shortened, six-month course of interferon and ribavirin will boost cure rates to 75% to 80%. Telaprevir+interferon+ribavirin will be the new standard of care for Hep C. [Merck's boceprevir plus standard of care should be in the mix, too.]
Look ahead a few more years. Pharmasset is dangling the prospect of an even simpler Hep C regimen: Two pills, taken once a day for six months providing odds of a cure as good as, perhaps even better, than what's achieved with the triple-drug telaprevir regimen.
As an encore of sorts, Pharmasset also wowed the EASL crowd with strong antiviral response data from studies combining PSI7977 with interferon and ribavirin. PSI7977 may be four or so years away from the market, but it's already looking like the next Hep C treatment standard bearer.
Little wonder Pharmasset shares continue to surge even after EASL ended. The stock closed Wednesday at $98.68 but was off 2% to $96 in mid-day trading Thursday. Still, remember Pharmasset shares were worth $50 one month ago.
Vertex emerged from EASL under more pressure to make the most of telaprevir commercially before competition arrives on the scene. Telaprevir is a major advance in Hep C treatment and the drug should pass easily through an April 28 FDA advisory panel and receive agency approval on or before May 23. As effective as the drug is for treatment-naive Hep C patients, the drug will have an even more beneficial effect for the hundreds of thousands of patients with Hep C virus that wasn't cured by the current standard of care.
Vertex's dilemma is that investors know this story well and have baked much of telaprevir's potential into the company's valuation already. What concerns investors today and perhaps even more post-EASL is that the slope of the expected telaprevir revenue tail may be steeper than previously appreciated. Investors are also raising questions about what Vertex is doing to sustain its Hep C franchise in 2015 and beyond when new drugs are expected to enter the market.
Looming largest in Vertex's rear-view mirror are Johnson & Johnson's(JNJ) TMC435 and perhaps Bristol-Myer Squibb's(BMY) BMS 052. [Worth noting, too, that Bristol-Myers and Pharmasset are already testing combinations of their respective Hep C drugs.]
Vertex is working on new combination therapies, too, but so far, the efforts haven't yielded much. A two-drug regimen of telaprevir plus VX-222 was shelved, leaving Vertex experimenting with a "quad" regimen of telaprevir, VX-222 plus standard of care.
VX-222 was highly touted as Vertex's next-generation Hep C drug candidate when it was picked up through the 2009 acquisition of privately held Virochem. Today, VX-222 isn't looking so hot, which means Vertex needs to license or buy something else if the company wants to stay in the Hep C game long term.
Roche is in desperate shape because Pegasys, the market-leading interferon, is going away. Roche bought InterMune's(ITMN) Hep C drug and licensed a first-generation drug from Pharmasset but neither of these compounds are working out as hoped.
Gilead Sciences(GILD) continues to make slow but steady progress. A late-starter to Hep C drug development, Gilead came out of EASL with progressively better data on multiple drug regimens although its programs are still early stage and lag the competition.
The smaller Hep C drug players -- Achillion Pharmaceuticals(ACHN), Inhibitex(INHX), Idenix Pharmaceuticals(IDIX) and Anadys(ANDS) -- emerge from EASL under more pressure to find partners or acquirers. Hep C is rapidly evolving into a market similar to HIV where winners have multiple drugs to play with and losers are the single-drug companies sitting alone on the sidelines. Roche, J&J, Merck and Vertex should all be motivated to make deals in the coming year.
Showing posts with label HCV DAA agents. Show all posts
Showing posts with label HCV DAA agents. Show all posts
Saturday, April 9, 2011
Sunday, April 3, 2011
Bristol Myers Squibb's BMS-790052 and BMS-650032 combo opens up new possibilites at EASL...
Wow. And I said it couldn't be done, that the possibilities were remote at best for an interferon-free DAA combination to cure HCV. Well, I'll gladly step up and dig in to my slice of Humble Pie, because this really is terrific news that quite possibly will open up a brand new treatment paradigm that sheds the side effect-laden burden of interferon, at least in some patients. BMS unleashed their Phase II data at EASL on the combination of their NS5A inhibitor BMS-790052 protease NS3 inhibitor BMS-650032 in patients that had been previously treated with the current standard of care therapy, peglyated-interferon plus ribavirin for 48 weeks. Out of the 11 patients who took took the drug combo without the inteferon component, five cleared virus at the end of treatment, and four of those remained undetectable 24 weeks after 24 weeks. In a similar patient population that received the drug combo plus peg and riba, 9 out 10 patients were cured. That's some potency right there. From a business perspective, it looks like the company is being extremely proactive in looking at partners to help fill the void between the pending launch of the first generation of DAA agents and BMS-790052 + BMS-650032. Pharmasset, which just announced positive two week data on their own interferon-free two drug combo PSI-938 and PSI-7977, might be looking mighty sexy to BMS at this point.
Bristol-Myers Squibb Co. (BMY)’s cocktail of two experimental drugs cured four hepatitis C patients in the first success for a therapy that excludes often-toxic existing drugs.
The combination had a higher rate of success when paired with the current standard treatment in the 21-person trial, curing nine of 10 patients, researchers said today at the Berlin meeting of the European Association for the Study of the Liver. The study points to the next generation of drugs for the evasive virus, said Mark Thursz, a professor of hepatology at Imperial College London and vice-secretary of EASL.
Bristol-Myers, based in New York, is among about a dozen companies trying to make better drug combinations that either include interferon, a decades-old shot that causes flu-like symptoms and only works in half of patients, or that replace interferon entirely. At stake is leadership in a market that Jefferies International Ltd. estimates may total $15 billion a year by 2019.
“This is perhaps one of the most exciting developments this year,” Thursz said in an interview. “For some patients who are not going to tolerate interferon, this is the light at the end of the tunnel.”
Bristol-Myers plans to begin the last trials required for regulatory approval this year, Douglas Manion, the drugmaker’s head of neuroscience and virology research, said in an interview.
Toughest-to-Treat
Today’s trial studied the Bristol-Myers drugs, BMS-790052 and BMS-650032, in patients for whom existing therapies hadn’t been successful, “the toughest-to-treat population,” Manion said.
Ten patients got the two drugs together with interferon and generic ribavirin. All showed no sign of the virus 12 weeks after the treatment was over. One patient had signs of virus at 24 weeks and was again virus-free in another follow-up test 35 days later.
Of 11 patients who took the Bristol-Myers combination alone, five had cleared the virus from their bodies at the end of treatment. Four remained virus-free after 24 weeks.
Patients may start treatment earlier if they aren’t faced with the toxic side effects of traditional hepatitis C drugs, said Howard Liang, a Boston-based analyst for Leerink Swann & Co., in an interview.
“If you have an interferon-free regimen, the market expands fairly dramatically,” Liang said.
Side Effects
Side effects of the existing interferon regimen are often severe enough to force patients to take time off work, said Charles Gore, president of the Geneva-based patient advocacy group World Hepatitis Alliance.
Roche Holding AG (ROG) of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey markets a form called PegIntron.
Merck, Vertex Pharmaceuticals Inc. (VRTX) and Johnson & Johnson are expected to bring the first new hepatitis C drugs in a decade to the market this year. About 90 percent of patients who responded quickly to treatment with Johnson & Johnson (JNJ) and Vertex’s telaprevir were cured, Cambridge, Massachusetts-based Vertex said in two studies last year. Three-quarters of all patients were cured. Patients who responded quickly to Merck’s boceprevir showed similarly high cure rates in studies last year, with about two-thirds of all patients being cured.
The Vertex and Merck trials included people who hadn’t yet been treated, an easier-to-cure group than those in today’s smaller study. By comparison, about 30 percent of those who hadn’t responded to previous treatment were cured after trying telaprevir plus standard therapy, researchers said.
Seeking Partners
Merck is seeking partnerships to gain its own hepatitis C drug combinations, Patrick Bergstedt, general manager of the infectious diseases franchise, said in an interview.
“We’re behind the others,” Bergstedt said. “We need to partner to fill the gap.”
Bristol-Myers expects an “element of consolidation” as companies use acquisitions, partnerships and research and development collaborations to gain their own hepatitis C drug combinations, Manion said. After signing a development deal with Princeton, New Jersey-based Pharmasset Inc. (VRUS) in January, Bristol- Myers is “talking to pretty much every company out there,” he said.
“This is like trying to redesign a car as you’re rolling down the road at 100 miles per hour, because the data are coming so fast,” he said. “What an exciting time.”
To contact the reporter on this story: Naomi Kresge in Frankfurt at nkresge@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Bristol-Myers Squibb Co. (BMY)’s cocktail of two experimental drugs cured four hepatitis C patients in the first success for a therapy that excludes often-toxic existing drugs.
The combination had a higher rate of success when paired with the current standard treatment in the 21-person trial, curing nine of 10 patients, researchers said today at the Berlin meeting of the European Association for the Study of the Liver. The study points to the next generation of drugs for the evasive virus, said Mark Thursz, a professor of hepatology at Imperial College London and vice-secretary of EASL.
Bristol-Myers, based in New York, is among about a dozen companies trying to make better drug combinations that either include interferon, a decades-old shot that causes flu-like symptoms and only works in half of patients, or that replace interferon entirely. At stake is leadership in a market that Jefferies International Ltd. estimates may total $15 billion a year by 2019.
“This is perhaps one of the most exciting developments this year,” Thursz said in an interview. “For some patients who are not going to tolerate interferon, this is the light at the end of the tunnel.”
Bristol-Myers plans to begin the last trials required for regulatory approval this year, Douglas Manion, the drugmaker’s head of neuroscience and virology research, said in an interview.
Toughest-to-Treat
Today’s trial studied the Bristol-Myers drugs, BMS-790052 and BMS-650032, in patients for whom existing therapies hadn’t been successful, “the toughest-to-treat population,” Manion said.
Ten patients got the two drugs together with interferon and generic ribavirin. All showed no sign of the virus 12 weeks after the treatment was over. One patient had signs of virus at 24 weeks and was again virus-free in another follow-up test 35 days later.
Of 11 patients who took the Bristol-Myers combination alone, five had cleared the virus from their bodies at the end of treatment. Four remained virus-free after 24 weeks.
Patients may start treatment earlier if they aren’t faced with the toxic side effects of traditional hepatitis C drugs, said Howard Liang, a Boston-based analyst for Leerink Swann & Co., in an interview.
“If you have an interferon-free regimen, the market expands fairly dramatically,” Liang said.
Side Effects
Side effects of the existing interferon regimen are often severe enough to force patients to take time off work, said Charles Gore, president of the Geneva-based patient advocacy group World Hepatitis Alliance.
Roche Holding AG (ROG) of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey markets a form called PegIntron.
Merck, Vertex Pharmaceuticals Inc. (VRTX) and Johnson & Johnson are expected to bring the first new hepatitis C drugs in a decade to the market this year. About 90 percent of patients who responded quickly to treatment with Johnson & Johnson (JNJ) and Vertex’s telaprevir were cured, Cambridge, Massachusetts-based Vertex said in two studies last year. Three-quarters of all patients were cured. Patients who responded quickly to Merck’s boceprevir showed similarly high cure rates in studies last year, with about two-thirds of all patients being cured.
The Vertex and Merck trials included people who hadn’t yet been treated, an easier-to-cure group than those in today’s smaller study. By comparison, about 30 percent of those who hadn’t responded to previous treatment were cured after trying telaprevir plus standard therapy, researchers said.
Seeking Partners
Merck is seeking partnerships to gain its own hepatitis C drug combinations, Patrick Bergstedt, general manager of the infectious diseases franchise, said in an interview.
“We’re behind the others,” Bergstedt said. “We need to partner to fill the gap.”
Bristol-Myers expects an “element of consolidation” as companies use acquisitions, partnerships and research and development collaborations to gain their own hepatitis C drug combinations, Manion said. After signing a development deal with Princeton, New Jersey-based Pharmasset Inc. (VRUS) in January, Bristol- Myers is “talking to pretty much every company out there,” he said.
“This is like trying to redesign a car as you’re rolling down the road at 100 miles per hour, because the data are coming so fast,” he said. “What an exciting time.”
To contact the reporter on this story: Naomi Kresge in Frankfurt at nkresge@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Sunday, March 20, 2011
Conatus Pharmaceuticals - Phase II data on Hepatitis C MMP inhibitor CTS-1027 to be presented at EASL
Privately-held Conatus Pharmaceuticals will have two posters on the Phase II trial of it's inhibitor of matrix metalloprotease (MMP) activity, CTS-1027 - the only MMP inhibitor currently in development for HCV at this time.
Conatus Pharmaceuticals Inc. today announced the acceptance of two poster presentations of Phase 2 clinical trial data of CTS-1027 for the treatment of hepatitis C virus-infected patients at the 46th annual meeting of the European Association for the Study of the Liver (EASL) to be held in Berlin, Germany, on March 30 to April 3, 2011.
Specifically, abstract 562 entitled: 24-WEEK TREATMENT WITH CTS-1027 IN COMBINATION WITH RIBAVIRIN REDUCES HCV-RNA IN TREATMENT NAIVE GENOTYPE-1 PATIENTS will be presented.
In addition, abstract 549 entitled: UNIQUE PATTERN OF VIROLOGIC RESPONSE IN PATIENTS WITH GENOTYPE-1 HCV: A PHASE II STUDY OF CTS-1027 IN COMBINATION WITH PEGINTEFERON/RIBAVIRIN (SOC) IN NULL RESPONDERS will also be presented.
"This will be the first public disclosure of these exciting clinical results and represents a significant step forward to raise awareness of CTS-1027 for the treatment of HCV," said Alfred P. Spada, Ph.D., Senior Vice President, Research and Development at Conatus.
"CTS-1027 is a first-in-class oral, small molecule inhibitor of host matrix metalloprotease (MMP) activity. There are no other drugs under development for HCV that operate by the same mechanism of action. Most other approaches to treat HCV infection are direct-acting anti-viral drugs whose activity is directed against virus proteins or enzymes with the objective of reducing the production of virus in infected cells. CTS-1027 by comparison is distinctly different in that its activity is hypothesized to facilitate the immune clearance of virus-infected cells and decrease the frequency of new infections, both of which are of key importance in curing HCV infections," said Steven J. Mento, Ph.D, President and CEO of Conatus.
Conatus Pharmaceuticals Inc. is a privately-held biopharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease and oncology. Conatus' lead drug candidate, CTS-1027 is in multiple Phase 2 clinical trials for the treatment of hepatitis C virus (HCV). Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the sale of Idun to Pfizer.
SOURCE Conatus Pharmaceuticals Inc.
Conatus Pharmaceuticals Inc. today announced the acceptance of two poster presentations of Phase 2 clinical trial data of CTS-1027 for the treatment of hepatitis C virus-infected patients at the 46th annual meeting of the European Association for the Study of the Liver (EASL) to be held in Berlin, Germany, on March 30 to April 3, 2011.
Specifically, abstract 562 entitled: 24-WEEK TREATMENT WITH CTS-1027 IN COMBINATION WITH RIBAVIRIN REDUCES HCV-RNA IN TREATMENT NAIVE GENOTYPE-1 PATIENTS will be presented.
In addition, abstract 549 entitled: UNIQUE PATTERN OF VIROLOGIC RESPONSE IN PATIENTS WITH GENOTYPE-1 HCV: A PHASE II STUDY OF CTS-1027 IN COMBINATION WITH PEGINTEFERON/RIBAVIRIN (SOC) IN NULL RESPONDERS will also be presented.
"This will be the first public disclosure of these exciting clinical results and represents a significant step forward to raise awareness of CTS-1027 for the treatment of HCV," said Alfred P. Spada, Ph.D., Senior Vice President, Research and Development at Conatus.
"CTS-1027 is a first-in-class oral, small molecule inhibitor of host matrix metalloprotease (MMP) activity. There are no other drugs under development for HCV that operate by the same mechanism of action. Most other approaches to treat HCV infection are direct-acting anti-viral drugs whose activity is directed against virus proteins or enzymes with the objective of reducing the production of virus in infected cells. CTS-1027 by comparison is distinctly different in that its activity is hypothesized to facilitate the immune clearance of virus-infected cells and decrease the frequency of new infections, both of which are of key importance in curing HCV infections," said Steven J. Mento, Ph.D, President and CEO of Conatus.
Conatus Pharmaceuticals Inc. is a privately-held biopharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease and oncology. Conatus' lead drug candidate, CTS-1027 is in multiple Phase 2 clinical trials for the treatment of hepatitis C virus (HCV). Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the sale of Idun to Pfizer.
SOURCE Conatus Pharmaceuticals Inc.
Thursday, March 10, 2011
EASL: Telaprevir in combination with Peg-INF2a and RBV increased SVR rates in treatment-naive patients regardless of race or ethnicity
Some impressive Telaprevir TVR) treatment naive pooled analysis data to be presented at the upcoming EASL meeting in Berlin, looking at SVR rate differences between race and ethnicity in the ADVANCE and ILLUMINATE trials. Specifically, differences between the TVR arms and Peg-inf2a/Ribavirin (PR). Most impressive were the differences in SVR, relapse and viral failure in Black/African American subjects. In the TVR + PR for 12 weeks, then PR for another 12 or 36 weeks depending on viral response, total SVR was 61%, relapse was 13% and viral failure was 9%. Compare this to the 48 week PR control arm, which showed 25% SVR, 36% relapse and 46% viral failure. Total TVR-related SVR was still lower than non-Black/African Americans (61% vs 75%, respectively) but the improvement from the current standard of care (48 weeks of PR) is significant and encouraging. See the full poster abstract here: http://www1.easl.eu/easl2011/program/Posters/Abstract222.htm
TELAPREVIR IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN INCREASED SUSTAINED VIROLOGIC RESPONSE RATES IN TREATMENT-NAïVE PATIENTS REGARDLESS OF RACE OR ETHNICITY
G.M. Dusheiko1*, M.W. Fried2, R. Reddy3, D.R. Nelson4, N. Bzowej5, N. Adda6, C.I. Wright6, L. Bengtsson6, S. George6, S.L. Flamm7
1Royal Free and University College, London, UK, 2University of North Carolina at Chapel Hill, Chapel Hill, NC, 3University of Pennsylvania School of Medicine, Philadelphia, PA, 4University of Florida, Gainesville, FL, 5California Pacific Medical Center, San Francisco, CA, 6Vertex Pharmaceuticals Incorporated, Cambridge, MA, 7Northwestern University, Chicago, IL, USA. *g.dusheiko@medsch.ucl.ac.uk
Background and aims: ADVANCE and ILLUMINATE were Phase 3 randomized studies that evaluated the safety and efficacy of telaprevir (T) in combination with peginterferon alfa-2a (P) and ribavirin (R) in treatment-naïve genotype 1 HCV patients. In this pooled analysis, we evaluated the effect of race or ethnicity on the response to treatment with telaprevir-based therapy.
Methods: Patients who received 12 weeks of response-guided telaprevir-based therapy for a total treatment duration of 24 or 48 weeks (ADVANCE N=903 and ILLUMINATE N=540) were compared to ADVANCE patients who received 48 weeks of PR alone (N=361). Race and ethnicity were self-reported and were not mutually exclusive. Ethnicity was not reported in 13 patients as the question was not allowed per local regulations.
Results: Efficacy outcomes are presented in the Table. The most common ( ≥ 25% in any subgroup) adverse events in patients who received telaprevir-based therapy were: fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, neutropenia, and diarrhea. Discontinuations of all drugs during telaprevir phase were: due to adverse events (7% in T12PR and 4% in PR), rash events (1% in T12PR and 0% in PR) and anemia events (1% in T12PR and < 1% in PR).
View table here: http://www1.easl.eu/easl2011/program/Posters/Abstract222.htm
Conclusions: Telaprevir-based therapy provided a substantial improvement in SVR rates in Black/African American and Hispanic/Latino patient populations known to achieve lower SVR rates when treated with PR alone. Low rates of discontinuations of all drugs due to adverse events, rash and anemia events were observed across all subgroups during the telaprevir phase.
TELAPREVIR IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN INCREASED SUSTAINED VIROLOGIC RESPONSE RATES IN TREATMENT-NAïVE PATIENTS REGARDLESS OF RACE OR ETHNICITY
G.M. Dusheiko1*, M.W. Fried2, R. Reddy3, D.R. Nelson4, N. Bzowej5, N. Adda6, C.I. Wright6, L. Bengtsson6, S. George6, S.L. Flamm7
1Royal Free and University College, London, UK, 2University of North Carolina at Chapel Hill, Chapel Hill, NC, 3University of Pennsylvania School of Medicine, Philadelphia, PA, 4University of Florida, Gainesville, FL, 5California Pacific Medical Center, San Francisco, CA, 6Vertex Pharmaceuticals Incorporated, Cambridge, MA, 7Northwestern University, Chicago, IL, USA. *g.dusheiko@medsch.ucl.ac.uk
Background and aims: ADVANCE and ILLUMINATE were Phase 3 randomized studies that evaluated the safety and efficacy of telaprevir (T) in combination with peginterferon alfa-2a (P) and ribavirin (R) in treatment-naïve genotype 1 HCV patients. In this pooled analysis, we evaluated the effect of race or ethnicity on the response to treatment with telaprevir-based therapy.
Methods: Patients who received 12 weeks of response-guided telaprevir-based therapy for a total treatment duration of 24 or 48 weeks (ADVANCE N=903 and ILLUMINATE N=540) were compared to ADVANCE patients who received 48 weeks of PR alone (N=361). Race and ethnicity were self-reported and were not mutually exclusive. Ethnicity was not reported in 13 patients as the question was not allowed per local regulations.
Results: Efficacy outcomes are presented in the Table. The most common ( ≥ 25% in any subgroup) adverse events in patients who received telaprevir-based therapy were: fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, neutropenia, and diarrhea. Discontinuations of all drugs during telaprevir phase were: due to adverse events (7% in T12PR and 4% in PR), rash events (1% in T12PR and 0% in PR) and anemia events (1% in T12PR and < 1% in PR).
View table here: http://www1.easl.eu/easl2011/program/Posters/Abstract222.htm
Conclusions: Telaprevir-based therapy provided a substantial improvement in SVR rates in Black/African American and Hispanic/Latino patient populations known to achieve lower SVR rates when treated with PR alone. Low rates of discontinuations of all drugs due to adverse events, rash and anemia events were observed across all subgroups during the telaprevir phase.
Tuesday, March 8, 2011
Could an all-oral agent to treat HCV be on the way?
Two week interim data for Pharmasset's Interferon/Ribavirin-free nuc-nuc combo is a long way from an SVR, but so far the company has earned bragging rights by having 15/16 subjects in this early phase trial go undetectable after two weeks. This is seemingly a pretty potent combo in comparison to Vertex's data with it's nuc VX-222 + Telaprevir + Peg Interferon + Ribavirin. Depending on the arm, that data topped out at 38-57% undetectability after 14 days in comparison to 94% with PSI-938 and PSI-7977. Pharmasset’s new landmark was enough for investors to spin like tops and goose the stock to new heights. Keep in mind that investors don’t always act rationally and It’s difficult to predict outcomes as all we know regarding viral kinetics and positive/negative predictive values comes from regimens that contain peg-inf plus ribavirin as its therapeutic backbone. If PSI-938 and PSI-7977 can retain 94% undetectable at four weeks, I’ll be proportionally reassured regarding this combo’s future. It will be interesting how the company defines when it’s time to stop therapy given that there isn’t an immunomodulator aboard. At what time points will the company declare EOT and SVR? An all oral combo would be an amazing paradigm shift for this disease state and will set the bar extremely high for drug developers looking to get into the HCV therapeutic category, but there’s a long road ahead.
Pharmasset Hep C Data Wows Investors
Adam Feuerstein
03/08/11 - 11:46 AM EST
PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.
Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.
These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.
Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.
The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.
EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.
While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.
None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.
Pharmasset owns full rights to both PSI-938 and PSI-7977. The company is developing another hepatitis C drug, RG7128, in partnership with Roche.
"We believe the full data of a 14-day combination of PSI-7977 / PSI-938 to be presented at the upcoming EASL could show proof of principle for a nuc-nuc combination and position Pharmasset as one of the front runners in the race to develop an interferon-free regimen, which is considered a Holy Grail in hepatitis C treatment," said Leerink Swann analyst Howard Liang in a note to clients Tuesday.
The EASL meeting at the end of the month will also feature data from other companies seeking to develop various combination treatments for hepatitis C.
Vertex Pharmaceuticals(VRTX) is studying a "quad" regimen consisting of two experimental drugs, VX-222 and telaprevir, combined with the current standard of care, long-acting interferon and ribavirin. An EASL research abstract released Monday reported treatment with Vertex's "quad" therapy resulted in 38-57% of patients with undetectable virus after two weeks and 86-87% undetectable after four weeks.
One potential competitive disadvantage to the Vertex quad is that patients still need to be treated with long-acting interferon, which requires weekly injections. Vertex previously reported disappointing results from an all-oral Hep C drug regimen that eliminated interferon.
Telaprevir is currently under review by regulators in the U.S. and Europe. The U.S. Food and Drug Administration is expected to make an approval decision on or before May 23.
Gilead Sciences(GILD) and Bristol-Myers Squibb(BMY) will also be presenting new data from Hep C combination drug studies at the EASL meeting later this month.
--Written by Adam Feuerstein in Boston.
Pharmasset Hep C Data Wows Investors
Adam Feuerstein
03/08/11 - 11:46 AM EST
PRINCETON, N.J. (TheStreet) -- Pharmasset(VRUS) shares are soaring on the release of new but very preliminary data that hints at a breakthrough, all-oral cure for hepatitis C.
Treatment with two oral drugs developed by Pharmasset resulted in 15 of 16, or 94%, of patients reporting undetectable levels of the hepatitis C virus after 14 days, according to interim results from a study released Monday.
These early data on the two Pharmasset drugs -- PSI-938 and PSI-7977 are the best reported to date by any company seeking to develop a new, all-oral therapy for hepatitis C. This Pharmasset effort is drawing even more attention because it potentially eliminates the need for patients to be treated with long-acting interferon, one of two drugs currently used to treat hepatitis C but which is difficult for patients to tolerate and causes many side effects.
Pharmasset shares rose 24% on Monday and were up another 8% to $66.92 on Tuesday.
The PSI-938 and PSI-7977 combination data were released Monday in a research abstract released online by the European Association for the Study of the Liver (EASL), which holds its annual meeting March 30 through April 3.
EASL makes research abstracts for its annual meeting freely available to the public but prohibits journalists from writing about the data contained in the research abstracts until they are presented at the annual meeting. TheStreet refuses to adhere to EASL's media embargo since these hepatitis C data are freely available online now and are impacting the stock prices of publicly traded companies developing hepatitis C drugs.
While investors are displaying great enthusiasm for the Pharmasset all-oral drug combination, the data from the study are very early. One particular risk seen in other, similar studies that omit long-acting interferon is the development of mutated hepatitis C virus that can quickly become resistant to drug treatment.
None of the patients treated in the Pharmasset study have reported rebounding levels of hepatitis C virus, according to the research abstract, but so-called viral rebound may emerge as patients are treated longer, or when treatment is stopped and these patients are followed long-term to determine if they are truly cured.
Pharmasset owns full rights to both PSI-938 and PSI-7977. The company is developing another hepatitis C drug, RG7128, in partnership with Roche.
"We believe the full data of a 14-day combination of PSI-7977 / PSI-938 to be presented at the upcoming EASL could show proof of principle for a nuc-nuc combination and position Pharmasset as one of the front runners in the race to develop an interferon-free regimen, which is considered a Holy Grail in hepatitis C treatment," said Leerink Swann analyst Howard Liang in a note to clients Tuesday.
The EASL meeting at the end of the month will also feature data from other companies seeking to develop various combination treatments for hepatitis C.
Vertex Pharmaceuticals(VRTX) is studying a "quad" regimen consisting of two experimental drugs, VX-222 and telaprevir, combined with the current standard of care, long-acting interferon and ribavirin. An EASL research abstract released Monday reported treatment with Vertex's "quad" therapy resulted in 38-57% of patients with undetectable virus after two weeks and 86-87% undetectable after four weeks.
One potential competitive disadvantage to the Vertex quad is that patients still need to be treated with long-acting interferon, which requires weekly injections. Vertex previously reported disappointing results from an all-oral Hep C drug regimen that eliminated interferon.
Telaprevir is currently under review by regulators in the U.S. and Europe. The U.S. Food and Drug Administration is expected to make an approval decision on or before May 23.
Gilead Sciences(GILD) and Bristol-Myers Squibb(BMY) will also be presenting new data from Hep C combination drug studies at the EASL meeting later this month.
--Written by Adam Feuerstein in Boston.
Wednesday, January 5, 2011
Anadys Pharmaceuticals intiates Phase IIb study of HCV Polymerase Inhibitor ANA598
Anadys getting it's non-nuc to Phase IIb, that's a pretty big hurdle for this company. If this gets to Phase III, they will have done what many drug developers previously have not. The Phase II graveyard for the DAA's is huge. Interesting that no week 4 (RVR) timepoint is mentioned for this protocol - Chris
SAN DIEGO, January 4, 2011 --Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it has initiated the planned Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin. The protocol for the study has been cleared by the United States Food and Drug Administration (FDA) and Health Canada. Patient screening has begun and patient dosing is expected to commence within the next several weeks. In the study ANA598 will be tested in both treatment-naïve patients and treatment-experienced patients who failed a prior course of therapy with interferon and ribavirin. ANA598 is the Company’s direct-acting antiviral, or DAA, being developed for the treatment of hepatitis C.
“We are excited to initiate this Phase IIb study of ANA598,” said James L. Freddo, M.D., Anadys’ Senior Vice President, Drug Development and Chief Medical Officer. “By establishing safety and efficacy in a greater number of patients, including those who have failed prior HCV treatment, we hope to position ANA598 as a highly attractive HCV agent ready for Phase III development.”
Phase IIb Protocol Design
In the study, approximately 200 chronically infected genotype 1 hepatitis C patients are expected to receive ANA598 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) with a loading dose of 800 mg bid on day 1, while approximately 66 patients are to receive placebo and SOC. Enrollment is expected to include approximately equal numbers of treatment-naïve patients and patients who have failed a prior course of SOC, including difficult to treat prior null-responders. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. Anadys is conducting the study at sites within and outside the United States.
Naïve Arm
Approximately 100 treatment-naïve HCV patients are expected to receive ANA598 in combination with SOC and 33 treatment-naïve HCV patients are to receive placebo plus SOC. Treatment duration for naïve patients will be response-guided; patients who achieve undetectable levels of virus at Week 8 and maintain undetectable levels of virus will be scheduled to conclude all treatment at Week 28. For naïve patients with detectable virus at Week 8 dosing with ANA598, or placebo, and SOC is planned to continue through Week 48. The Company expects to receive Week 8 antiviral response data by the end of the second quarter of 2011, Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
Treatment-Experienced Arm, Including Prior Null Responders
Approximately 80 patients who were partial responders during, or relapsers after, a prior course of therapy with SOC alone are expected to receive ANA598 in combination with SOC, and 33 corresponding patients are to receive placebo plus SOC. Additionally, approximately 28 prior null responder patients are to receive ANA598 in combination with SOC. All treatment-experienced patients who receive ANA598 are scheduled to receive triple combination therapy for 48 weeks. For the treatment-experienced patients, the Company expects to receive Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
SAN DIEGO, January 4, 2011 --Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that it has initiated the planned Phase IIb study of ANA598 in combination with pegylated interferon and ribavirin. The protocol for the study has been cleared by the United States Food and Drug Administration (FDA) and Health Canada. Patient screening has begun and patient dosing is expected to commence within the next several weeks. In the study ANA598 will be tested in both treatment-naïve patients and treatment-experienced patients who failed a prior course of therapy with interferon and ribavirin. ANA598 is the Company’s direct-acting antiviral, or DAA, being developed for the treatment of hepatitis C.
“We are excited to initiate this Phase IIb study of ANA598,” said James L. Freddo, M.D., Anadys’ Senior Vice President, Drug Development and Chief Medical Officer. “By establishing safety and efficacy in a greater number of patients, including those who have failed prior HCV treatment, we hope to position ANA598 as a highly attractive HCV agent ready for Phase III development.”
Phase IIb Protocol Design
In the study, approximately 200 chronically infected genotype 1 hepatitis C patients are expected to receive ANA598 200 mg twice a day (bid) in combination with Pegasys® (peginterferon alfa2a) and Copegus® (ribavirin, USP) (a current standard of care, or SOC) with a loading dose of 800 mg bid on day 1, while approximately 66 patients are to receive placebo and SOC. Enrollment is expected to include approximately equal numbers of treatment-naïve patients and patients who have failed a prior course of SOC, including difficult to treat prior null-responders. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients conclude all treatment, known as SVR24. Anadys is conducting the study at sites within and outside the United States.
Naïve Arm
Approximately 100 treatment-naïve HCV patients are expected to receive ANA598 in combination with SOC and 33 treatment-naïve HCV patients are to receive placebo plus SOC. Treatment duration for naïve patients will be response-guided; patients who achieve undetectable levels of virus at Week 8 and maintain undetectable levels of virus will be scheduled to conclude all treatment at Week 28. For naïve patients with detectable virus at Week 8 dosing with ANA598, or placebo, and SOC is planned to continue through Week 48. The Company expects to receive Week 8 antiviral response data by the end of the second quarter of 2011, Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
Treatment-Experienced Arm, Including Prior Null Responders
Approximately 80 patients who were partial responders during, or relapsers after, a prior course of therapy with SOC alone are expected to receive ANA598 in combination with SOC, and 33 corresponding patients are to receive placebo plus SOC. Additionally, approximately 28 prior null responder patients are to receive ANA598 in combination with SOC. All treatment-experienced patients who receive ANA598 are scheduled to receive triple combination therapy for 48 weeks. For the treatment-experienced patients, the Company expects to receive Week 12 antiviral response data in the third quarter of 2011 and Week 24 antiviral response data in the fourth quarter of 2011.
Monday, December 20, 2010
Idera Pharmaceuticals reports positive antiviral results from phase 1 study for Hep C drug
Idera Pharmaceuticals (Nasdaq: IDRA) announced Monday positive preliminary results from a phase 1 study for IMO-2125, the company's investigational drug treatment for chronic hepatitis C infection.
Hep C is an infectious disease affecting the liver. It is often asymptomatic, but once established, chronic infection can progress to scarring of the liver. In some cases, people will go on to develop liver failure or other complications, including liver cancer.
During the 4-week dose-ranging trial, the IMO-2125 drug was tested in combination with ribavirin, in 60 patients with the virus. The results indicated a "substantial decline" in virus levels at two days after the first dose of IMO-2125, and after four weeks of treatment, the company said.
In addition, liver enzymes decreased during the treatment period and were within the normal range by the end of the fourth week in the majority of IMO-2125-treated patients.
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said vice president of clinical development, Robert Arbeit.
Idera develops drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs).
TLRs, a family of immune system receptors and the immune system's first line of defense, recognize pathogens, or infectious agents, and initiate an immune response.
IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines, or protein regulating molecules.
The company said it is now planning a 12-week phase 2 trial of the drug, which it expects will determine optimal dosing and provide longer term safety and antiviral activity data. Recruitment for the study is anticipated to begin in the first quarter of next year.
Idera was up more than 7% on Monday morning, trading at $2.53 as of 11:30am EST
Hep C is an infectious disease affecting the liver. It is often asymptomatic, but once established, chronic infection can progress to scarring of the liver. In some cases, people will go on to develop liver failure or other complications, including liver cancer.
During the 4-week dose-ranging trial, the IMO-2125 drug was tested in combination with ribavirin, in 60 patients with the virus. The results indicated a "substantial decline" in virus levels at two days after the first dose of IMO-2125, and after four weeks of treatment, the company said.
In addition, liver enzymes decreased during the treatment period and were within the normal range by the end of the fourth week in the majority of IMO-2125-treated patients.
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said vice president of clinical development, Robert Arbeit.
Idera develops drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs).
TLRs, a family of immune system receptors and the immune system's first line of defense, recognize pathogens, or infectious agents, and initiate an immune response.
IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines, or protein regulating molecules.
The company said it is now planning a 12-week phase 2 trial of the drug, which it expects will determine optimal dosing and provide longer term safety and antiviral activity data. Recruitment for the study is anticipated to begin in the first quarter of next year.
Idera was up more than 7% on Monday morning, trading at $2.53 as of 11:30am EST
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