Posted today on US & World News.com . Full article to be published in the journal 'Proceedings of the National Academy of Sciences'. Add 'iPSCs' to your lexicon of HCV-related verbiage. Induced Pluripotent Stem Cells are culled from body tissues rather than human embryos and offer scientists the ability to great liver-like cells which can then be infected with the HCV virus. Liver cells are difficult to obtain and grow in vitro, so scientists are hoping that this new method will allow them to gain insight into the genetic factors which play a role in disease progression.
Stem Cells May Further Hepatitis C Research
Using liver-like cells, scientists hope to learn how some people resist infection
January 31, 2012
TUESDAY, Jan. 31 (HealthDay News) -- Using stem cells to create liver-like cells for laboratory research may advance efforts to find out why people respond differently to hepatitis C infection, scientists say.
It's not clear why some people are resistant to hepatitis C, while others are highly susceptible to the infectious disease that can cause liver inflammation and organ failure.
Studying liver cells from various people could reveal genetic factors behind these different responses, but liver cells are difficult to obtain and to grow in a lab dish.
Now, U.S. researchers have found a way to create liver-like cells from induced pluripotent stem cells (iPSCs), which are made from body tissues rather than embryos. These liver-like cells can then be infected with hepatitis C.
The research was published Jan. 30 in the journal Proceedings of the National Academy of Sciences.
It's the first time that scientists have been able to establish an infection in iPSC-derived cells. The technique was developed by a team from MIT, Rockefeller University and the Medical College of Wisconsin.
Along with benefiting hepatitis C research, the new technique may eventually have a role in personalized medicine, the researchers said in a MIT news release. By testing the effectiveness of different drugs on tissues derived from a patient, doctors could customize therapy for that patient, they said.
Tuesday, January 31, 2012
'The Street' on the decline of Incivek...
Posted today on The Street.com . The author believes that Incivek's sales may have peaked in the 4th quarter of 2011 at lower-than-forecasted sales numbers. This may be due to a new 'watch and wait' period as providers hold off treatment for those that they feel can wait for the 2nd generation of HCV DAA drugs which hold promise for improved tolerability and dosing schedules. Also contributing to the negative slope are those that have treated HCV patients with Incivek and found that managing patients was more hands on than they had anticipated and those providers that may have been inclined to treat, but were turned off to doing so as negative rumors circulated. Economic issues may play a factor here as well - reimbursement rates for HCV care are less-than-ideal, formulary access is spotty and the cost of treating with Telaprevir is a head-spinning sum.
Vertex Hep C Sales Growth Nears End
By Adam Feuerstein
CAMBRIDGE, Mass. (TheStreet) --Vertex Pharmaceuticals'(VRTX_) fourth-quarter earnings report Thursday may represent the high-water sales mark for the hepatitis C drug Incivek -- with prescriptions already declining just seven months after launch.
Current consensus estimate for fourth-quarter 2011 Incivek sales is $483 million, down from more than $500 million earlier this month.
If Vertex meets lowered sales expectations, Incivek will still deliver its best-ever quarter. After that, Incivek sales in the current quarter and through the rest of 2012 are expected to flatten out, perhaps fall, as doctors slow their use of the drug. Hepatitis C patients who can afford to delay treatment may wait for the arrival of new, all-oral regimens expected in 2013-2014.
Before anyone throws a pity party for Vertex, some perspective is in order. Incivek, even with flat prescriptions and sales, is still a cash-generating machine for Vertex. The drug is on pace to record close to $1 billion in sales in 2011 -- amazing since it was only approved on May 23.
In 2012, Incivek will deliver sales around $2 billion, according to the most current consensus estimate. [Vertex has not yet provided 2012 sales guidance but may do so on Thursday.] The only reason that's bad is because many investors on Wall Street tend to value quarter-over-quarter sales growth over everything else. An Incivek year with flattish sequential revenue, even if that revenue totals $2 billion, just doesn't ring the bell for many institutional investors.
Vertex shares at $34.74 are up 5% since the start of the year but are down 40% from their peak right before Incivek was approved last May. That's investors baking in Incivek's relatively short revenue stream. The worst is expected so if Incivek outperforms lowered forecasts or if competing next-generation Hep C drugs from Gilead Sciences or Bristol-Myers Squibb falter, Vertex could very easily rebound in a big way.
Vertex is not ceding the race to develop an all-oral Hep C regimen to its rivals. Later this quarter, Vertex will announce early cure rates from a phase II study of triple therapy that combines Incivek, the experimental pill VX-222 and ribavirin. In the second quarter, the company will release the first proof-of-concept data on two Hep C "nucs" licensed from Alios Biopharma.
Vertex Hep C Sales Growth Nears End
By Adam Feuerstein
CAMBRIDGE, Mass. (TheStreet) --Vertex Pharmaceuticals'(VRTX_) fourth-quarter earnings report Thursday may represent the high-water sales mark for the hepatitis C drug Incivek -- with prescriptions already declining just seven months after launch.
Current consensus estimate for fourth-quarter 2011 Incivek sales is $483 million, down from more than $500 million earlier this month.
If Vertex meets lowered sales expectations, Incivek will still deliver its best-ever quarter. After that, Incivek sales in the current quarter and through the rest of 2012 are expected to flatten out, perhaps fall, as doctors slow their use of the drug. Hepatitis C patients who can afford to delay treatment may wait for the arrival of new, all-oral regimens expected in 2013-2014.
Before anyone throws a pity party for Vertex, some perspective is in order. Incivek, even with flat prescriptions and sales, is still a cash-generating machine for Vertex. The drug is on pace to record close to $1 billion in sales in 2011 -- amazing since it was only approved on May 23.
In 2012, Incivek will deliver sales around $2 billion, according to the most current consensus estimate. [Vertex has not yet provided 2012 sales guidance but may do so on Thursday.] The only reason that's bad is because many investors on Wall Street tend to value quarter-over-quarter sales growth over everything else. An Incivek year with flattish sequential revenue, even if that revenue totals $2 billion, just doesn't ring the bell for many institutional investors.
Vertex shares at $34.74 are up 5% since the start of the year but are down 40% from their peak right before Incivek was approved last May. That's investors baking in Incivek's relatively short revenue stream. The worst is expected so if Incivek outperforms lowered forecasts or if competing next-generation Hep C drugs from Gilead Sciences or Bristol-Myers Squibb falter, Vertex could very easily rebound in a big way.
Vertex is not ceding the race to develop an all-oral Hep C regimen to its rivals. Later this quarter, Vertex will announce early cure rates from a phase II study of triple therapy that combines Incivek, the experimental pill VX-222 and ribavirin. In the second quarter, the company will release the first proof-of-concept data on two Hep C "nucs" licensed from Alios Biopharma.
Monday, January 30, 2012
Cell Permeable Peptide Identified that Inhibits Hepititis C Replication...
Posted today on Health News Digest.com and published in the Jan 30 issue of 'Hepatology'. UCLA researchers identify heat shock proteins (HSPs) that are important for viral infection and that the natural compound Quercetin inhibits synthesis of these proteins In Vitro.
Cell Permeable Peptide Identified that Inhibits Hepititis C Replication...
By Staff Editor
Jan 30, 2012 - 3:23:54 PM
Discovery Could Lead to a New Treatment for a Disease that Impacts up to 160 Million People Worldwide
(HealthNewsDigest.com) - Researchers from UCLA’s Jonsson Comprehensive Cancer Center have identified a cell-permeable peptide that inhibits a hepatitis C virus protein and blocks viral replication, which can lead to liver cancer and cirrhosis.
This finding by Dr. Samuel French, an assistant professor of pathology and senior author of the study, builds on previous work by the French laboratory that identified two cellular proteins that are important factors in hepatitis C virus infection.
French and his team initially set out to identify the cellular factors involved in hepatitis C replication and, using mass spectrometry, found that heat shock proteins (HSPs) 40 and 70 were important for viral infection. HSP70 was previously known to be involved, but HSP40 was linked for the first time to hepatitis C infection, French said. They further showed that the natural compound Quercetin, which inhibits the synthesis of these proteins, significantly inhibits viral infection in tissue culture.
In this study, published Jan. 30, 2012 in the peer-reviewed journal Hepatology, French and his team demonstrated that the viral non-structural protein 5A (NS5A) directly binds to HSP70 and mapped the site of the NS5A/HSP70 complex on NS5A. While HSP70 was previously shown to bind NS5A in cells, a direct NS5A/HSP70 interaction and complex formation was established in this study. In an effort to stop this interaction, they tested peptides that might inhibit HSP70.
“This is important because we’ve developed a small peptide that binds to that site and blocks the interaction between the proteins that is important for viral replication,” French said. “This is another, potentially highly efficacious way to block replication of hepatitis C.”
An estimated 160 million people worldwide are infected with hepatitis C and the conventional treatments – interferon and ribavirin – can have significant side effects. A new drug targeting cellular proteins rather than viral proteins would be a valuable addition to the treatment arsenal, French said.
“We were surprised that this peptide works this well,” French said. “While its mechanism is different, the activity of this peptide is comparable to other newly developed anti-virals.”
The study, done in tissue culture, shows that the peptide gains entry into the cell easily and blocks the cascade of cellular events that allows the virus to replicate, French said. Blocking the HSP70 protein rather than a viral protein also reduces the chance of patients with the hepatitis C virus developing resistance to the peptide.
“There’s no direct pressure on the virus, so it is less likely to mutate and develop resistance,” French said. “The goal is to achieve a sustained response, essentially a cure, meaning there is no more virus replication. There are a lot of drugs coming out now that are designed to stop hepatitis C replication, but resistance is still an issue. About 10 to 20 percent of patients on the new drugs become resistant. This new peptide may help combat resistance.”
Going forward, French and his team are testing variants of the newly discovered peptide to see if they can develop one with an even higher affinity and can decrease the size of the peptide to improve cellular penetration and liver targeting. The new and improved peptides will be tested in animal models.
This peptide “may be a candidate for hepatitis C therapy,” the study states. “Considering the potency of the peptide in suppressing viral translation levels, treatment with this peptide may significantly improve the efficacy of conventional treatments in patients who become resistant to conventional therapies.”
The study was supported in part by the National Institutes of Health and by the California Center for Antiviral Drug Discovery at the University of California.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.
Cell Permeable Peptide Identified that Inhibits Hepititis C Replication...
By Staff Editor
Jan 30, 2012 - 3:23:54 PM
Discovery Could Lead to a New Treatment for a Disease that Impacts up to 160 Million People Worldwide
(HealthNewsDigest.com) - Researchers from UCLA’s Jonsson Comprehensive Cancer Center have identified a cell-permeable peptide that inhibits a hepatitis C virus protein and blocks viral replication, which can lead to liver cancer and cirrhosis.
This finding by Dr. Samuel French, an assistant professor of pathology and senior author of the study, builds on previous work by the French laboratory that identified two cellular proteins that are important factors in hepatitis C virus infection.
French and his team initially set out to identify the cellular factors involved in hepatitis C replication and, using mass spectrometry, found that heat shock proteins (HSPs) 40 and 70 were important for viral infection. HSP70 was previously known to be involved, but HSP40 was linked for the first time to hepatitis C infection, French said. They further showed that the natural compound Quercetin, which inhibits the synthesis of these proteins, significantly inhibits viral infection in tissue culture.
In this study, published Jan. 30, 2012 in the peer-reviewed journal Hepatology, French and his team demonstrated that the viral non-structural protein 5A (NS5A) directly binds to HSP70 and mapped the site of the NS5A/HSP70 complex on NS5A. While HSP70 was previously shown to bind NS5A in cells, a direct NS5A/HSP70 interaction and complex formation was established in this study. In an effort to stop this interaction, they tested peptides that might inhibit HSP70.
“This is important because we’ve developed a small peptide that binds to that site and blocks the interaction between the proteins that is important for viral replication,” French said. “This is another, potentially highly efficacious way to block replication of hepatitis C.”
An estimated 160 million people worldwide are infected with hepatitis C and the conventional treatments – interferon and ribavirin – can have significant side effects. A new drug targeting cellular proteins rather than viral proteins would be a valuable addition to the treatment arsenal, French said.
“We were surprised that this peptide works this well,” French said. “While its mechanism is different, the activity of this peptide is comparable to other newly developed anti-virals.”
The study, done in tissue culture, shows that the peptide gains entry into the cell easily and blocks the cascade of cellular events that allows the virus to replicate, French said. Blocking the HSP70 protein rather than a viral protein also reduces the chance of patients with the hepatitis C virus developing resistance to the peptide.
“There’s no direct pressure on the virus, so it is less likely to mutate and develop resistance,” French said. “The goal is to achieve a sustained response, essentially a cure, meaning there is no more virus replication. There are a lot of drugs coming out now that are designed to stop hepatitis C replication, but resistance is still an issue. About 10 to 20 percent of patients on the new drugs become resistant. This new peptide may help combat resistance.”
Going forward, French and his team are testing variants of the newly discovered peptide to see if they can develop one with an even higher affinity and can decrease the size of the peptide to improve cellular penetration and liver targeting. The new and improved peptides will be tested in animal models.
This peptide “may be a candidate for hepatitis C therapy,” the study states. “Considering the potency of the peptide in suppressing viral translation levels, treatment with this peptide may significantly improve the efficacy of conventional treatments in patients who become resistant to conventional therapies.”
The study was supported in part by the National Institutes of Health and by the California Center for Antiviral Drug Discovery at the University of California.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.
Vertex stock falls as Leerink Swann reduces sales forecast for Telaprevir...
Posted on Business Week today. Leerink Swann analyst cut his sales forecast for Telaprevir by 35% and target share price from $66 to $48 based on the current hyper-aggressive development space for interferon-free therapy. It was only a matter of time once Pharmasset launched their broadside at AASLD 2011. This is a ground-breaking product, but burdened with a sharply curtailed life cycle.
Vertex Falls as Analyst Cuts Hep C Sales Estimate: Boston Mover
January 30, 2012, 6:40 PM EST
By Drew Armstrong
Jan. 30 (Bloomberg) -- Vertex Pharmaceuticals Inc. fell the most in seven weeks after an analyst with Leerink Swann & Co. cut sales estimates for a hepatitis C pill made by the company that was approved by U.S. regulators last year.
Vertex’s Incivek, among the first new hepatitis C drugs to reach the market in almost a decade, may be eclipsed by new pill-only treatments with fewer side effects and shorter courses of treatment. Incivek is given with interferon, an injected medicine. Merck & Co.’s similar pill, Victrelis, was also approved last year.
Shares of Cambridge, Massachusetts-based Vertex fell 3.5 percent to $34.74 at the close in New York, their biggest one- day drop since Dec. 8.
Howard Liang, an analyst with Leerink Swann in Boston, reduced his sales forecast for Incivek by 35 percent from $2.3 billion this year to $1.5 billion. Liang also cut his target price for Vertex shares from $66 to $48.
“In light of recent development of interferon-free regimens and likely more aggressive development as a result of recent transactions in the space, we are further curtailing the Incivek tail,” Liang said in a note to clients today.
Vertex had $420 million in revenue from Incivek in the third quarter of 2011. Revenue from the drug accounts for 64 percent of the company’s sales.
--Editors: Angela Zimm, Adriel Bettelheim
To contact the reporter on this story: Drew Armstrong in Washington at darmstrong17@bloomberg.net;
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Vertex Falls as Analyst Cuts Hep C Sales Estimate: Boston Mover
January 30, 2012, 6:40 PM EST
By Drew Armstrong
Jan. 30 (Bloomberg) -- Vertex Pharmaceuticals Inc. fell the most in seven weeks after an analyst with Leerink Swann & Co. cut sales estimates for a hepatitis C pill made by the company that was approved by U.S. regulators last year.
Vertex’s Incivek, among the first new hepatitis C drugs to reach the market in almost a decade, may be eclipsed by new pill-only treatments with fewer side effects and shorter courses of treatment. Incivek is given with interferon, an injected medicine. Merck & Co.’s similar pill, Victrelis, was also approved last year.
Shares of Cambridge, Massachusetts-based Vertex fell 3.5 percent to $34.74 at the close in New York, their biggest one- day drop since Dec. 8.
Howard Liang, an analyst with Leerink Swann in Boston, reduced his sales forecast for Incivek by 35 percent from $2.3 billion this year to $1.5 billion. Liang also cut his target price for Vertex shares from $66 to $48.
“In light of recent development of interferon-free regimens and likely more aggressive development as a result of recent transactions in the space, we are further curtailing the Incivek tail,” Liang said in a note to clients today.
Vertex had $420 million in revenue from Incivek in the third quarter of 2011. Revenue from the drug accounts for 64 percent of the company’s sales.
--Editors: Angela Zimm, Adriel Bettelheim
To contact the reporter on this story: Drew Armstrong in Washington at darmstrong17@bloomberg.net;
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Saturday, January 28, 2012
Celgene buys it's way into a feverish Hepatitis C market...
An article from Investor's Business Daily on recent biotech mergers, including Celgene's recent purchase of Avila Therapeutics, which may also put Celgene in the HCV DAA marketplace. I need a scorecard to keep up!
Gilead, Celgene Join Big Pharma On M&A Front
By MARILYN ALVA, INVESTOR'S BUSINESS DAILY Posted 01/27/2012 02:19 PM ET
The biotech industry is gripped with acquisition fever.
Celgene (CELG) was the latest to catch the fever, announcing Thursday it would buy privately held Avila Therapeutics for $350 million.
The move expands Celgene's market-leading blood cancer arsenal, which includes top-gun Revlimid, by adding Avila's experimental drug therapy known as AVL-292, now in clinical development.
Gene mapping is making drug development more precise, targeting patients with certain genetic markers.
Avila also brings Celgene into the hot hepatitis C treatment arena with drugs called protease inhibitors now in preclinical development.
Biotech firms are racing to bring new hepatitis C drugs to market to replace the current regimen of virus-fighting cocktails, including injectable interferon, which often has crippling side effects.
The Celgene/Avila deal is small potatoes compared with HIV-focused Gilead Sciences' (GILD) recent acquisition of Pharmasset.
Gilead paid $11.2 billion, a huge premium, to get its hands on the company's hepatitis C drugs still in development.
The deal was unusual not only for its size, but also for the type of outfit doing the buying: another biotech firm.
Biotech mergers and acquisitions are not new. But biotech firms usually make smaller buys.
It's the large diversified drug firms that typically pay big money for biotech firms to offset blockbuster drugs losing patent protection and shrinking development pipelines.
Last year, France's Sanofi-Aventis (SNY) paid $20 billion for the remaining interest it had in Genzyme.
In 2009, Swiss drug giant Roche Holding (RHHBY) bought Genentech, the granddaddy of biotechs, for a cool $46.8 billion, giving it reason to declare itself the biggest biotech company in the world.
"Gilead's $11 billion acquisition really opened eyes for the potential of biotech companies to be big acquirers as well," said Steven Silver, biotech equity analyst with S&P Capital IQ.
Gilead, and now Celgene, are among a host of companies buying their way into new treatments for the hepatitis C virus, which affects liver function and afflicts some 170 million people worldwide.
Big Pharma is also on the hepatitis C warpath. In early January, Bristol-Myers Squibb (BMY) said it would pay $2.5 billion for biotech firm Inhibitex (INHX) to expand its war chest of hepatitis C drugs in development.
Its announcement came after Roche agreed to buy biotech outfit Anadys Pharmaceuticals (ANDS) for $250 million to bolster its hepatitis C pipeline.
"The hot theme for mergers and acquisitions right now is hepatitis C," said Silver.
Gilead, Celgene Join Big Pharma On M&A Front
By MARILYN ALVA, INVESTOR'S BUSINESS DAILY Posted 01/27/2012 02:19 PM ET
The biotech industry is gripped with acquisition fever.
Celgene (CELG) was the latest to catch the fever, announcing Thursday it would buy privately held Avila Therapeutics for $350 million.
The move expands Celgene's market-leading blood cancer arsenal, which includes top-gun Revlimid, by adding Avila's experimental drug therapy known as AVL-292, now in clinical development.
Gene mapping is making drug development more precise, targeting patients with certain genetic markers.
Avila also brings Celgene into the hot hepatitis C treatment arena with drugs called protease inhibitors now in preclinical development.
Biotech firms are racing to bring new hepatitis C drugs to market to replace the current regimen of virus-fighting cocktails, including injectable interferon, which often has crippling side effects.
The Celgene/Avila deal is small potatoes compared with HIV-focused Gilead Sciences' (GILD) recent acquisition of Pharmasset.
Gilead paid $11.2 billion, a huge premium, to get its hands on the company's hepatitis C drugs still in development.
The deal was unusual not only for its size, but also for the type of outfit doing the buying: another biotech firm.
Biotech mergers and acquisitions are not new. But biotech firms usually make smaller buys.
It's the large diversified drug firms that typically pay big money for biotech firms to offset blockbuster drugs losing patent protection and shrinking development pipelines.
Last year, France's Sanofi-Aventis (SNY) paid $20 billion for the remaining interest it had in Genzyme.
In 2009, Swiss drug giant Roche Holding (RHHBY) bought Genentech, the granddaddy of biotechs, for a cool $46.8 billion, giving it reason to declare itself the biggest biotech company in the world.
"Gilead's $11 billion acquisition really opened eyes for the potential of biotech companies to be big acquirers as well," said Steven Silver, biotech equity analyst with S&P Capital IQ.
Gilead, and now Celgene, are among a host of companies buying their way into new treatments for the hepatitis C virus, which affects liver function and afflicts some 170 million people worldwide.
Big Pharma is also on the hepatitis C warpath. In early January, Bristol-Myers Squibb (BMY) said it would pay $2.5 billion for biotech firm Inhibitex (INHX) to expand its war chest of hepatitis C drugs in development.
Its announcement came after Roche agreed to buy biotech outfit Anadys Pharmaceuticals (ANDS) for $250 million to bolster its hepatitis C pipeline.
"The hot theme for mergers and acquisitions right now is hepatitis C," said Silver.
Thursday, January 26, 2012
Top Hepatitis C Virus Biotech Picks By The World's Largest Fund Managers
Recently posted on the Seeking Alpha.com financial website on who fund managers like in the HCV drug development space. In general, fund managers are bullish like Idenix, Dynavax and Peregrine but the currently bears run wild for Vertex, Achillion and Merck. Good quick rundown of what each company specializes in and where they're HCV compounds are in terms of development and partnerships.
The announcement by Bristol-Myers Squibb (BMY), just over two weeks ago, on January 7th, of an agreement to buy Inhibitex (INHX) for $2.5 billion at a massive buyout premium of over 160%, has ignited a rally among biotech companies that are currently active in developing products targeting hepatitis C virus (HCV). In this article, we examine based on our research of their latest available Q3 institutional 13-F filings, the investment activities of the world's largest funds or mega funds among a dozen pharmaceutical and biotech companies that are active in the HCV space.
These mega fund managers hold between $100 billion and over a trillion dollars in assets, such as Fidelity Investments, Goldman Sachs, and Vanguard Group, and together they control almost a third of the assets invested in the U.S. equity markets, but number just over 30 out of the tens of thousands of funds that invest in the U.S. equity markets. Individually, and collectively, they pack enough firepower to move stocks based on their trading activities.
Taken together, these mega managers were bullish on the group, adding a net $427 million in Q3 to their prior $178.84 billion prior quarter holdings in the group. However, taking out the big pharmaceutical companies, mega funds still added a net $530 million in Q3 to their $47.46 billion prior quarter position among the biotech companies that are active in the HCV field. (for more general information on these mega funds, please look at the end of the article).
The following are the HCV group companies that mega fund managers are bullish about (see Table):
Idenix Pharmaceuticals (IDIX): IDIX engages in the discovery and development of drugs for the treatment of human viral and other infectious diseases, including a focus on hepatitis C virus, hepatitis B virus (HBV), human immunodeficiency virus (HIV) type-1, and acquired immune deficiency syndrome (AIDS). Mega funds added a net $45 million in Q3 to their $380 million prior quarter position, and together they hold 29.7% of the outstanding shares, higher than their 26.3% weighting in the group. The top mega fund buyers in Q3 was by Fidelity Investments ($50 million), and the top holders were Fidelity Investments ($131 million), T Rowe Price ($114 million) and Vanguard Group ($50 million).
IDIX shares have mounted a strong rally recently, up more than 100% in the past twelve trading days, benefiting from both the January 9th announcement of the acquisition of rival INHX by BMY that has ignited a rally in the group, as well as positive interim phase 2b clinical trial data on its HCV Nucleotide Inhibitor, IDIX 184, that was released the same day by the company.
Dynavax Technologies (DVAX): DVAX is a clinical-stage biotech company that is engaged in the discovery and development of novel products to prevent and treat infectious and inflammatory diseases. Its lead clinical stage product candidate is HEPLISAV™, a phase 3 investigational adult hepatitis B vaccine designed to provide protection with fewer doses than current licensed vaccines. In addition it has early stage product candidates, including a universal flu vaccine in phase 1, TLR inhibitor for lupus in phase 1, and then hepatitis B and hepatitis C therapies, also in phase 1 development.
Mega funds added a net $7 million in Q3 to their $102 million prior quarter position, and taken together they hold 25.8% of outstanding shares. The top mega fund buyers were Fidelity Investments ($3.3 million) and Bank of America Corp. ($1.6 million), and the top holder by far was also Fidelity Investments ($64 million). DVAX is currently engaged in preparing to submit its first Biologics License Application (BLA) for HEPLISAV™ Hepatitis B Vaccine to the FDA in the first quarter of 2012, followed soon by a submission of Marketing Authorization Application (MAA) for European approval.
Peregrine Pharmaceuticals (PPHM): PPHM is a clinical-stage biotech company developing and manufacturing innovative monoclonal antibody therapeutics to treat cancers and viral infections such as hepatitis C virus. In the hepatitis C space, the company is evaluating bavituximab combined with ribavirin in a randomized phase 2 trials in treatment native patients with genotype-1 HCV infection. Earlier, the company released preliminary phase 2 trial results from this study on December 29th last year that showed antiviral activity and a positive safety profile, with patients reporting fewer side effects than in the interferon-containing arm. Mega funds added a net $1 million in Q3 to their $8 million prior quarter position, and taken together mega funds hold 11.4% of the outstanding shares, with the top holders at the end of Q3 being Barclays Global Investors ($2.7 million) and Blackrock ($1.7 million).
The following are the HCV group companies that mega fund manager are most bearish about (see Table):
Vertex Pharmaceuticals (VRTX): VRTX engages in the discovery, development, and commercialization of small molecule drugs for the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases. It has two FDA-approved drugs, INCIVEKTM for treat chronic hepatitis C genotype-1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatments, and Lexiva for HIV that it co-discovered with GlaxoSmithKline (GSK).
It has five other drugs in clinical development, including VX-222 in phase 2 development for hepatitis C, VX-765 in phase 2 development for epilepsy, VX-509 in phase 2 development for immune-mediated inflammatory disease, and VX-770 and VX-809 in phase 3 and phase 2 development respectively for Cystic Fibrosis. Mega funds cut a net $110 million in Q3 form their $3.89 billion prior quarter position. The top sellers were Fidelity Investments ($91 million) and T Rowe Price ($34 million), and the top holders were Fidelity Investments ($966 million) and Capital World Investors ($653 million).
Achillion Pharmaceutical (ACHN): ACHN is a clinical-stage biotech focused on developing new treatments to patients with infectious diseases, including HCV and resistant bacterial infections. It currently has five compounds in various stages of clinical development targeting HCV, including one in phase 2, two in phase 1 and two others in pre-clinical development. Mega funds cut a net $6 million from their $280 million prior quarter position, with the top seller being Bank of New York Mellon Corp. ($18 million), and the top holder being Fidelity Investments ($111 million). ACHN shares rallied strongly after the announcement of the INHX acquisition by BMY, up over 50% in the five trading days after the January 7th announcement; while they have given back part of their gains, they are still up over 35% on the news.
Inhibitex Inc. and Bristol-Myers Squibb Co.: INHX, a developer of differentiated anti-infective products to prevent and treat serious viral and bacterial infections, including primarily shingles and chronic infections caused by hepatitis C virus, is under agreement to be acquired by BMY, a developer of branded pharmaceuticals for the treatment of cardiovascular, virological and other infectious diseases. Mega funds cut $28 million in Q3 from a $512 million prior quarter position in INHX, and they added a net $711 million to their $20.51 billion prior quarter position in BMY.
Other pharmaceutical and biotech companies that are players in the HCV space that mega funds are bearish on (see Table) include Gilead Sciences Inc. (GILD), that has multiple product candidates in phase 1 and phase 2 trials targeting hepatitis C, in which mega funds cut a net $306 million in Q3 from their $17.68 billion prior quarter position, and Abbott Laboratories (ABT), that has a product candidate in phase 2 clinical trials for HCV in collaboration with Enanta Pharmaceuticals, in which mega funds cut a net $16 million in Q3 from their $26.63 billion prior quarter position.
Also, additional HCV players that mega funds are bullish about include Merck & Co. (MRK), that has an FDA-approved product Victrelis for HCV in the market, and several in phase 2 and 3 development for hepatitis B and C, in which mega funds added a net $530 million to their $47.46 billion prior quarter position; and Pfizer Inc. (PFE), that has a compound in phase 2 development for HCV, in which mega funds added a net $60 million to their $54.03 billion prior quarter position. Furthermore, mega funds have a $1 million position, unchanged in Q3, in Inovio Pharmaceuticals (INO), that has compounds in phase 2 and preclinical development targeting HCV.
General Methodology and Background Information: The latest available institutional 13-F filings of over 30+ mega hedge fund and mutual fund managers were analyzed to determine their capital allocation among different industry groupings, and to determine their favorite picks and pans in each group. These mega fund managers number less than one percent of all funds and yet they control almost half of the U.S. equity discretionary fund assets. The argument is that mega institutional investors have the resources and the access to information, knowledge and expertise to conduct extensive due diligence in informing their investment decisions. When mega Institutional Investors invest and maybe even converge on a specific investment idea, the idea deserves consideration for further investigation. The savvy investor may then leverage this information either as a starting point to conduct his own due diligence.
Credit: Historical fundamentals including operating metrics and stock ownership information were derived using SEC filings data, I-Metrix® by Edgar Online®, Zacks Investment Research, Thomson Reuters and Briefing.com. The information and data is believed to be accurate, but no guarantees or representations are made.
Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
Disclaimer: Material presented here is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. Further, these are our 'opinions' and we may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given in this article. If this makes you uncomfortable, then do not listen to our thoughts and opinions. The contents of this article do not take into consideration your individual investment objectives so consult with your own financial adviser before making an investment decision. Investing includes certain risks including loss of principal.
Tuesday, January 24, 2012
BMS Phase II DAA-only Proof of Principle regimen published in the New England Journal Of Medicine...
Apologies for the lack of activity, just back from a great, relaxing vacation in Kauai. Once the plane landed at LAX, I was immediately stressed-out again. It's amazing how fast the return to status quo occurs post-vacation.
On to the big news regarding the synergistic combination of BMS's investigational NS5A inhibitor, Daclatasvir and NS3 protease inhibitor, Asunaprevir both with and without the addition of pegylated interferon and ribavirin. This is old news by now to the HCV infomaniacs who frequent this blog and others, but is notable in that BMS is the first to have their proof of principle phase II data using just a combination of two DAA agents (no ribavirin or pegylated interferon in the mix) to achieve an SVR12 of 36% in null responder patients, 100% SVR12 in this same population with the addition of ribavirin and pegylated interferon. To put into perspective how powerful these two agents appear to be, keep in mind that a casual comparison to Telaprevir plus P/R in a similar patient population generated an SVR of ~ 33% (never a good idea to causally compare anything, let alone two separate clinical trials, but it gives us a ballpark estimate for general potency). One hopes that the addition of a third drug in the Daclatasvir and Asunaprevir combination targeting an additional part of the HCV life cycle could raise the SVR12 rate significantly above 36%. For the time being, however, it looks like pegylated interferon and ribavirin in combination with these two powerful DAA drugs are essential components in preventing resistance in this patient population. This fact also further bodes well for BMS in that, unless I lost track somewhere, they are also the owners of PEG-lamda which potentially has a leg-up in terms of efficacy and tolerability over the current pegylated interferons currently on the market. I haven't heard much about their plans for PEG-lamda development lately. Feel free to correct or update me if I missed something.
press release
Jan. 18, 2012, 5:01 p.m. EST
First Hepatitis C Treatment Data Demonstrating Proof of Principle with Direct-Acting Antiviral-only Therapy Published
Study also Demonstrated 100% Sustained Virologic Response 12-Weeks Post Treatment with Quadruple Therapy
PRINCETON, N.J., Jan 18, 2012 (BUSINESS WIRE) -- --Phase II Investigational Data Published Today in the New England Journal of Medicine
Bristol-Myers Squibb Company today announced the full results, published in the New England Journal of Medicine, from a Phase II clinical trial in patients with hepatitis C virus (HCV) genotype 1 who had not responded to prior therapy with PEG-interferon alfa and ribavirin ('null responders'(1)). The study demonstrated that its primary endpoint of the achievement of sustained virologic response 12-weeks post-treatment (SVR12) is possible with a direct-acting antiviral (DAA)-only combination containing daclatasvir and asunaprevir (4/11 patients, including two of two patients infected with HCV genotype 1b). This study was the first study to demonstrate the possibility that hepatitis C can be cured (defined as sustained virologic response 48 weeks post-treatment or SVR48) without the use of interferon. The study also demonstrated that 100 percent (10/10) of these difficult-to-treat patients dosed with quadruple therapy containing daclatasvir and asunaprevir in combination with PEG-Interferon alfa and ribavirin achieved SVR12.
In this study there were no serious adverse events on treatment or discontinuations due to adverse events. Diarrhea was the most common adverse event in both groups (73% and 70%).
"Even with the recent approval of two protease inhibitors, treatment of hepatitis C patients who have not responded to PEG-interferon alfa and ribavirin has limited success. Because of this high unmet medical need, there is a necessity for new combination regimens that can increase response rates in null responders," said lead investigator Anna Lok, MD, FRCP, director of clinical hepatology and professor in the department of internal medicine at the University of Michigan Medical School in Ann Arbor. "The data seen in this study with Bristol-Myers Squibb's investigational DAAs daclatasvir and asunaprevir, either as DAA-only therapy or as part of quadruple therapy, are encouraging as we work to advance hepatitis C therapy for this difficult-to-treat patient population. This study also shows for the very first time that sustained viral responses can be achieved without the use of interferon and ribavirin."
Daclatasvir is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. Asunaprevir is an investigational, oral, selective NS3 protease inhibitor.
Study Results
Viral Response: Dual DAA Therapy with daclatasvir and asunaprevir (Group A)
Eleven patients were randomized to receive dual DAA therapy for 24 weeks. Seven of the 11 patients (64%) in Group A achieved undetectable viral load by week four, and five patients remained undetectable at the end of treatment. Of these 11 patients, one patient relapsed at four (4) weeks post treatment while four patients (36%) had sustained virological response at 12 weeks post-treatment (SVR12). In follow-up to 48-weeks post treatment, no additional cases of viral relapses were observed.
Six patients, all with HCV genotype 1a, experienced viral breakthrough on dual DAA therapy, and analysis of HCV sequences following breakthrough confirmed resistance to both antivirals. With the addition of PEG-interferon alfa and ribavirin to their regimen (rescue therapy), four of the six patients achieved undetectable viral load. Two of these patients relapsed following the treatment period and two remained undetectable, one with 14 weeks and one with 42 weeks of post treatment follow-up. Two of the six patients did not achieve undetectable HCV RNA and treatment was discontinued.
Viral Response: Quadruple Therapy with daclatasvir, asunaprevir and PEG-Interferon alfa and ribavirin (Group B)
Ten patients were randomized to receive quadruple therapy for 24-weeks. Six of the 10 patients (60%) in Group B achieved undetectable HCV RNA by week four. Ten of the 10 patients (100%) were undetectable by the end of treatment, and all 10 achieved SVR12. No patients experienced viral relapse during 48 weeks of post-treatment observation.
Safety
In the study, there were no serious adverse events on treatment, no deaths, and no treatment discontinuations due to adverse events. Most adverse events were mild to moderate, and the most common AEs were diarrhea (group a:8/11)(group a:73%)(group b:7/10)(group b:70%), fatigue (group a:6/11)(group a:55%)(group b:7/10)(group b:70%), headache (group a:5/11)(group a:45%)(group b:5/10)(group b:50%), and nausea (group a:2/11)(group a:18%)(group b:5/10)(group b:50%).
Six patients (four from group A, including two receiving rescue therapy, and two from group B) experienced elevated liver enzymes [ALT >3x upper limit of normal (ULN)] which did not require treatment discontinuation or dose interruptions, and all patients stabilized or improved with continued therapy. Six patients, all of whom received PEG-interferon alfa and ribavirin, experienced Grade 3 or 4 neutropenia, a blood disorder characterized by an abnormally low number of white blood cells.
About the Study
This open-label, phase IIa study evaluated the antiviral activity and safety of the combination of daclatasvir and asunaprevir with and without PEG-Interferon alfa and ribavirin in 21 HCV genotype 1 null responders. Patients in the study were randomized to receive one of two treatment regimens for 24 weeks. The 11 patients in Group A received dual-DAA therapy with daclatasvir 60 mg once daily and asunaprevir 600 mg twice daily, both taken orally. The 10 patients in Group B received quadruple therapy with daclatasvir 60 mg once daily, asunaprevir 600 mg twice daily, PEG-interferon alfa 180 ug once weekly, and ribavirin 1000-1200 mg daily (according to body weight) in two divided doses. The primary study objective was to determine the proportion of patients achieving undetectable viral load (HCV RNA <10 IU/mL) 12 weeks post-treatment (SVR12). This dual-DAA combination is now in Phase III development.
About Bristol-Myers Squibb's Commitment to Liver Disease
Bristol-Myers Squibb is advancing a portfolio of compounds that aims to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. The Company's hepatitis C pipeline includes a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials and is currently in Phase III development. Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor in Phase III development for hepatitis C.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews .
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compound described in this release will move from exploratory development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
(1) Null responders -- patients whose virus did not respond to prior treatment with PEG-interferon alfa and ribavirin (HCV RNA decrease <2 log10 at 12 weeks).
SOURCE: Bristol-Myers Squibb Company
2012 Annual CCO HIV and Hepatitis C Symposium: Implementing Best Practices in HIV, HCV, and Coinfection
Register today for this weekend-long annual symposium covering the year’s most important new advances in the treatment of HIV and hepatitis C. Designed for frontline clinicians treating HIV- or HCV-monoinfected and/or coinfected patients, the highly interactive program features plenary presentations, interactive case discussions, and roundtable sessions reviewing the most up-to-date clinical information. Please check the Web site for the latest information on the confirmed agenda and faculty.
The Westin Diplomat
3555 South Ocean Drive
Hollywood, Florida
New CCO Module: Update of HCV Resistance from AASLD 2011
New Clinical Care Options CME Module now online: Update on HCV Resistance from AASLD 2011
Christoph Sarrazin, MD, reviews new data on resistance to direct-acting antiviral agents from the 2011 American Association for the Study of Liver Diseases conference. (Registration required)
Topics covered include:
New data on resistance to boceprevir and telaprevir
New data on resistance to second-wave and second-generation HCV protease inhibitors
Key findings on resistance to daclatasvir, an NS5A inhibitor
Current understanding of resistance to PSI-7977, a nucleotide polymerase inhibitor
New data on resistance to oral combination HCV therapies
Saturday, January 14, 2012
Idenix seeks a partner for IDX184...
From Bloomberg News: Idenix CEO Ron Renaud announces they need a protease inhibitor or NS5A inhibitor-weilding partner for their HCV nuc, IDX184. Analysts speculate that Tibotec or Merck may be attractive partners.
Idenix Seeks Partner for Hepatitis C Combination Drug, CEO Renaud Says
By Sasha Damouni - Jan 13, 2012 1:05 PM PT .
...
Idenix Pharmaceuticals Inc. (IDIX), the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.
“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”
The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.
The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”
Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.
Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. (BMY) said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. (GILD) for $10.8 billion.
Safer Treatments
As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.
On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.
“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.
While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.
Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world’s biggest health-care products company, also may have an interest because of its hepatitis C research program.
To contact the reporter on this story: Sasha Damouni in New York at sdamouni2@bloomberg.net
To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net; Brad Skillman at bskillman1@bloomberg.net
Idenix Seeks Partner for Hepatitis C Combination Drug, CEO Renaud Says
By Sasha Damouni - Jan 13, 2012 1:05 PM PT .
...
Idenix Pharmaceuticals Inc. (IDIX), the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.
“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”
The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.
The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”
Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.
Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. (BMY) said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. (GILD) for $10.8 billion.
Safer Treatments
As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.
On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.
“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.
While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.
Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world’s biggest health-care products company, also may have an interest because of its hepatitis C research program.
To contact the reporter on this story: Sasha Damouni in New York at sdamouni2@bloomberg.net
To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net; Brad Skillman at bskillman1@bloomberg.net
Thursday, January 12, 2012
Gilead nears completion of Pharmasset deal
From Boston.com: Gilead edges closer to acquiring Pharmasset and it's prized portfolio of HCV drugs. I can smell the co-formulations brewing from here.
Gilead nears completion of Pharmasset deal
January 12, 2012
FOSTER CITY, Calif.—Gilead Sciences has acquired about 95 percent of the outstanding shares in Pharmasset as it draws closer to closing its $11 billion deal for the drug developer.
Gilead, based in Foster City, Calif., said about 72 million Pharmasset shares have been tendered. Gilead announced in November that it would pay $137 per share in cash for the, a Princeton, N.J. drug developer.
Pharmasset Inc. has three potential hepatitis C treatments in clinical testing, including a candidate labeled PSI-7977 in late-stage testing. Analysts see promise in the drug because doctors may be able prescribe the pill in a combination with other treatments that does not involve interferon, an injection that comes with rough side effects.
Hepatitis C is a virus that can lead to life-threatening liver damage and is the main cause of liver transplants in the United States. Analysts expect it to become a bigger health problem as baby boomers ages.
Gilead Sciences Inc. plans to buy additional shares of Pharmasset directly from the company, which has no drugs on the market. The acquisition is expected to close in the first quarter.
Wednesday, January 11, 2012
Achillion Pharmaceuticals updates investors on HCV protease inhibitor portfolio...
From RTT News: Short blurb on Achillion's HCV protease inhibitor portfolio - ACH-1625 and ACH-2684
Achillion Pharmaceuticals (ACHN) Rose Above Resistance At The Highs
1/10/2012 6:51 AM ET
(RTTNews) - Achillion Pharmaceuticals (ACHN: News ) reported new clinical trial results on its portfolio of protease inhibitors Monday morning. Based upon the results, the company is planning further exploration of ACH-1625 in combination with other oral antiviral agents for the treatment of all HCV genotypes and continues to evaluate ACH-2684 in a Phase 1 clinical trial.
Achillion Pharmaceuticals gapped open higher Monday and climbed further around the middle of the afternoon. The stock finished up by 1.80 at $9.72, with volume at a 6-month high. Achillion broke out of a 2 1/2 week range and set a new high for the year.
Merck's high hopes for Hepatitis C market dominance...
An article from the San Francisco Chronicle (via Bloomberg news) on Merck's high hopes to be the leader in HCV antivirals. While their current HCV protease inhibitor Victrelis is running a distant second in the overall market compared to Vertex Pharmaceutical's Incivek, Merck has gained some traction with Victrelis thanks to a market backlash to Vertex. Some of Incivek's side effects have far outpaced what was seen in their clinical trials, drawing the ire of concerned HCV providers and HCV advocates. Merck's protease inhibitor MK-5172, currently in early clinical trials certainly seems to be potent with a reported 5 log drop in viral load in 3 day monotherapy trials. As for it's potential to be a leading 'anchor drug' in the marketplace, only time will tell.
Merck & Co. aims to be hepatitis C global leader
Robert Langreth, Bloomberg News
Wednesday, January 11, 2012
Merck & Co. will make whatever deals are necessary to ensure the company leads the race for future hepatitis C combination therapies, said Roger Pomerantz, the drugmaker's worldwide head of licensing and acquisitions.
"Our goal is to be a leader in hepatitis C, and we will do what it takes to get there," Pomerantz said in an interview at the JP Morgan Healthcare Conference in San Francisco. "We would consider small deals to large deals, whatever is necessary to lead in hepatitis."
Victrelis OKd in May
Merck, the second-biggest U.S. drugmaker after Pfizer Inc., won U.S. approval in May for Victrelis, the first hepatitis C drug in almost a decade. The company's pill and Vertex Pharmaceuticals Inc.'s Incivek, cleared for sale just 10 days after Victrelis, are easier to use and have fewer side effects than the standard injection treatments for the liver disease. Now the company is in the second stage of testing for a more powerful drug that may work against all strains of the virus, Pomerantz said Monday.
If trials are successful for the drug, called MK-5172, the therapy may become the foundation medicine for future combination pill treatments, he said.
An 'anchor' drug
"What we have seen makes us quite optimistic that the drug could be an anchor," he said.
As many as 170 million people worldwide carry the hepatitis C virus, a blood-borne disease that can lead to liver cirrhosis and cancer, according to the Centers for Disease Control and Prevention in Atlanta. The new pills, used in combination with the injectable treatments, have a higher cure rate than previous therapies alone. Incivek and Victrelis are so-called protease inhibitors that work by blocking an enzyme used by the hepatitis C virus to copy itself.
The market for medicines against the disease is about $3 billion worldwide, according to Andrew Berens, a senior health-care analyst with Bloomberg Industries. It may be worth $20 billion by 2020, said Michael Kishbauch, chief executive officer of Achillion Pharmaceuticals Inc., the maker of another experimental treatment, in a November interview.
The race to gain an all-pill regimen for hepatitis C has led to two recent deals. Bristol-Myers Squibb Co. said Jan. 7 it would pay about $2.5 billion in cash to buy Inhibitex Inc. Pharmasset agreed to be acquired by Foster City's Gilead Sciences Inc. for $10.8 billion in a deal announced Nov. 21.
Idenix Pharmaceuticals Inc., which also has a hepatitis C drug candidate, and Achillion rose in trading on speculation they may be acquired like Inhibitex and Pharmasset. Idenix and Achillion on Monday also reported successful results of early clinical trials for their experimental drugs.
Achillion is "not eager to go out and plant a 'for sale' sign on our front lawn," Mary Kay Fenton, the company's chief financial officer, said Monday in an interview at the health care conference. Instead, Achillion is concentrating on developing its drug candidates, she said.
Market data provided by Bloomberg News
Merck & Co. aims to be hepatitis C global leader
Robert Langreth, Bloomberg News
Wednesday, January 11, 2012
Merck & Co. will make whatever deals are necessary to ensure the company leads the race for future hepatitis C combination therapies, said Roger Pomerantz, the drugmaker's worldwide head of licensing and acquisitions.
"Our goal is to be a leader in hepatitis C, and we will do what it takes to get there," Pomerantz said in an interview at the JP Morgan Healthcare Conference in San Francisco. "We would consider small deals to large deals, whatever is necessary to lead in hepatitis."
Victrelis OKd in May
Merck, the second-biggest U.S. drugmaker after Pfizer Inc., won U.S. approval in May for Victrelis, the first hepatitis C drug in almost a decade. The company's pill and Vertex Pharmaceuticals Inc.'s Incivek, cleared for sale just 10 days after Victrelis, are easier to use and have fewer side effects than the standard injection treatments for the liver disease. Now the company is in the second stage of testing for a more powerful drug that may work against all strains of the virus, Pomerantz said Monday.
If trials are successful for the drug, called MK-5172, the therapy may become the foundation medicine for future combination pill treatments, he said.
An 'anchor' drug
"What we have seen makes us quite optimistic that the drug could be an anchor," he said.
As many as 170 million people worldwide carry the hepatitis C virus, a blood-borne disease that can lead to liver cirrhosis and cancer, according to the Centers for Disease Control and Prevention in Atlanta. The new pills, used in combination with the injectable treatments, have a higher cure rate than previous therapies alone. Incivek and Victrelis are so-called protease inhibitors that work by blocking an enzyme used by the hepatitis C virus to copy itself.
The market for medicines against the disease is about $3 billion worldwide, according to Andrew Berens, a senior health-care analyst with Bloomberg Industries. It may be worth $20 billion by 2020, said Michael Kishbauch, chief executive officer of Achillion Pharmaceuticals Inc., the maker of another experimental treatment, in a November interview.
The race to gain an all-pill regimen for hepatitis C has led to two recent deals. Bristol-Myers Squibb Co. said Jan. 7 it would pay about $2.5 billion in cash to buy Inhibitex Inc. Pharmasset agreed to be acquired by Foster City's Gilead Sciences Inc. for $10.8 billion in a deal announced Nov. 21.
Idenix Pharmaceuticals Inc., which also has a hepatitis C drug candidate, and Achillion rose in trading on speculation they may be acquired like Inhibitex and Pharmasset. Idenix and Achillion on Monday also reported successful results of early clinical trials for their experimental drugs.
Achillion is "not eager to go out and plant a 'for sale' sign on our front lawn," Mary Kay Fenton, the company's chief financial officer, said Monday in an interview at the health care conference. Instead, Achillion is concentrating on developing its drug candidates, she said.
Market data provided by Bloomberg News
Monday, January 9, 2012
Pharmalot's Ed Silverman comments on the "White Hot Hep C Market"...
Pharmalot's Ed Silverman on the 'white hot' HCV marketplace. Are we seeing Greenspan's famous 'irrational exuberence' as it applies to the market for Hepatitis C compounds? Is big pharma ponying up too much money too soon for drugs with very little human clinical experience or is this the way of the future as Big Pharma R&D budgets are sliced in favor of purchasing small to mid-size biotechs for their short and near -term pipelines?
A White Hot Hep C Market: What The Wags Say
By Ed Silverman // January 9th, 2012 // 11:52 am
Over the weekend, Bristol-Myers Squibb agreed to pay $2.5 billion in cash for Inhibitex, which has completed only Phase I testing for its Hepatitis C compound. The deal, which some Wall Streeters speculate may invite a bidding war, underscores the extent to which Hepatitis C has become one of the hottest playgrounds for the pharmaceutical industry.
Two months ago, for instance, Gilead Sciences paid $11 billion for Pharmasset, which had finished proof of concept Phase II studies (read this). And last spring, Merck won approval for a new Hepatitis C treatment and then quicky turned around and struck a collaboration with Roche (see here), just days before Vertex Pharmaceuticals also received FDA endorsement for a drug.
But does the Bristol-Myers deal make sense? What about the Gilead deal? Where does this leave Merck? And what might happen next? These were among the questions that, not surprisingly, several Wall Street analysts were attempting to answer this morning as they pondered the Inhibitex purchase and the Hepatitis C market. Here are a few of their thoughts:
The price tag for Inhibitex, Bernstein Research analyst Tim Bernstein writes is “very expensive.” Nonetheless, he notes that virology has been a “core therapeutic area” for the drugmaker and may have been interested in purchasing Pharmasset, but did not want to pony up a huge amount to “round out” its product portfolio.
On the downside, it may be quite a while before anyone can determine whether this is a good deal, because the Inhibitex compound is in such an early stage of development. By contrast, he notes that Bristol-Myers paid $2 billion for Medarex in 2009 and, roughly two years later, the Yervoy treatment for melanoma was approved and on the market.
“At this point, among Hepatitis C drug developers, it is not known which exact combination of agents will be the most effective, but a common goal is to use an all-oral regimen that can eliminate the need for interferon, to better improve tolerability,” he writes. “In general, Hepatitis C is becoming a very crowded space and it will be difficult to predict which companies or compounds might be the ultimate ‘winners,’ and there is an arms race between market participants to flesh out their portfolios and have as many complementary shots on goal as possible.”
Meanwhile, RW Baird analyst Tom Russo posits that the deal is fair, but fully valued, when balancing the recent positives for the Inhibitex compounds and the “the potentially transformative value” of using a nucleotide polymerase inhibitor in Hepatits C treatment against further development risks. He notes that intellectual property constraints mean that there are relatively few “nucs” in development.
“The dynamic of many to few – as in many big players committed to HCV but few small, attractive pure-plays – creates a very favorable dynamic,” he writes, adding that the short list of other potential acquisitions leaves Achillion Pharmaceuticals and Idenix Pharmaceuticals. “Big Pharma generally prefers to wait for more complete de-risking, but we’ve wondered if an offsetting sense of urgency – to act before all the best assets are gone – was setting in, and the move by Bristol-Myers following fast on the heels of Gilead could amplify this.
And Leerink Swann analyst Howard Liang writes that the purchase price for Inhibitex may be “unprecedented for an early Phase II asset,” but the deal was probably “necessary for Bristol-Myers to remain relevant” in the Hepatitis C market. “We view (the) acquisition as tacit admission of the importance of ‘nucs’ to the development of all oral Hepatitis C therapies. While this will be viewed as a risky move by most, we believe it likely was a necessary move for Bristol-Myers to remain relevant… if ‘nucs’ are a critical backbone and the Inhibitex compound is safe enough.”
In his view, Bristol-Myers was one of the most “critical companies, scientifically, on the safety of nucs, so its willingness to step forward suggests nucs will clearly be critical to all oral regimens and the (Inhibitex compound) may be used for a short enough duration to be safe and effective.” Separately, he says this narrows Merck’s options for adding a nuc, although it is not yet “checkmate.”
He speculates that Merck may wind up partnering with Bristol-Myers or Gilead, but the big drugmaker is “clearly is at a strategic disadvantage” if ‘nucs’ prove to be as important as Pharmasset acquisition seems to imply.
'The Street' contributor Adam Feuerstein on IDX184...
The Street.com's Adam Feuerstein puts his 2 cents in on Idenix's IDX184 nucleoside analog, who came back from the dead after the FDA suspended a trial involving IDX184 and protease inhibitor IDX320 (plus peg and riba) in September of 2010 after three healthy volunteers experienced elevated liver enzymes. It's now clear that IDX184 appears to be safe, but there are questions regarding it's potency, especially in light of recent data from Pharmasset's PSI-7977 and Inhibitex's INX-189 which may put it at a possible competitive disadvantage. To throw my 2 cents in and add to the kitty, 'safe' is really a good thing in this space looking at the Phase II wasteland of HCV drugs. All these second generation drugs still have a way to go in development. If developers are betting on a 'nuc' backbone, the drug that ultimately has the best safety profile may garner itself a competitive advantage, even if it takes a bit longer to clear virus
Idenix Pharma's Hep C Drug Safe But Slow (And Ready For Sale)
SAN FRANCISCO (TheStreet) -- Idenix Pharmaceuticals'(IDIX_) experimental hepatitis C drug IDX184 looks to be safe (whew!) but doesn’t appear to work particularly fast (uh oh….)
On Monday morning, relief over the apparently clean safety report for IDX184 combined with a healthy dose of hepatitis C drug takeover speculation was all the fuel needed to send Idenix shares up $2.84, or 43%, to $10 in the pre-market session. [Achillion Pharmaceuticals(ACHN_) share, likewise, are up 35% to $10.65 on takeover speculation and positive data reported on its pipeline of hepatitis C drugs.]
Idenix's lead drug, IDX184, belongs to the same "nucleoside" or "nuc" class of oral Hep C drugs as Pharmasset's PSI-7977 and Inhibitex's INX-189. Since both were acquired for huge premiums recently, popular thinking is that Idenix's turn at the altar is imminent.
After 31 hepatitis C patients completed 28 days of treatment with IDX184 in combination with weekly interferon and ribavirin, no serious adverse events were reported and an independent safety monitoring board recommended that more patients can be enrolled in the phase II study, Idenix said Monday.
Based on this clean safety report, Idenix plans to ask U.S. regulators to remove a clinical hold on IDX184 put in place last year. The company reported the new IDX184 in advance of its presentation this afternoon at the J.P. Morgan Healthcare Conference.
Idenix said that 73% of patients treated with a 100 mg dose of IDX184 reported undetectable levels of the hepatitis C virus after 28 days. At a median treatment duration of 8 weeks in the study, 87% of these patients are now undetectable.
For patients treated with a lower, 50 mg dose of IDX184, 63% were undetectable at 28 days and 94% were undetectable at a median treatment duration of 8 weeks. None of these patients in the study have so far reported a re-emergence of the hepatitis C virus in their systems.
These efficacy data suggest that IDX184 works slower and perhaps is not as potent as the competing "nucs" being developed by Pharmasset and Inhibitex. For example, Pharmasset's PSI-7977 demonstrated a 4-week early response rate of 98% in a similar setting and patient population. Moreover, Idenix enrolled relatively healthier hepatitis C patients for this initial IDX184 study, suggesting that the drug may further underperform when hepatitis C patients with more advanced disease are treated.
"For us, this trial was about solidifying the safety profile of IDX184 as much as anything else. We believe we have demonstrated that and hope the FDA agrees with us. Our goal is to get to interferon-free regimens as soon as possible," said Idenix CEO Ron Renaud, in an email.
Renaud downplayed questions about the speed at which IDX184 can clear the hepatitis C virus, arguing that combinations of different types of oral drugs will likely be needed ultimately, but it's not clear yet what those combinations might be.
It's certainly true that big players in the race to develop an all-oral hepatitis C therapy --Bristol-Myers Squibb, Gilead Sciences most prominently -- are betting on a "nuc" being the backbone of whatever regimen emerges. And right now, Idenix is sitting on a nuc -- IDX184 -- that appears safe and is certainly available to any interested bidder for the right price.
Sunday, January 8, 2012
BMS bolsters HCV competetive postion with the purchase of Inhibitex...
From Market Watch.com - BMS takes another step to bolster its burgeoning HCV product portfolio with the purchase of Georgia-based Inhibitex. Inhibitex's pipeline includes the promising (at least, at this point) pan-genotypic NS5B inhibitor, INX-189 currently in phase II trials. This follows the jaw-dropping acquisition of Pharmasset and it's HCV pipeline by Gilead in November. Just as Aristotle once proposed that the character of a man is revealed by his actions, It's becoming increasingly clear which organizations are serious about being contenders in the HCV therapeutic space. This is a very interesting time for this pioneering treatment space and an indication of how lucrative - and brutally competitive - this space is becoming.
NEW YORK & PRINCETON, N.J. & ATLANTA, Jan 07, 2012 (BUSINESS WIRE) -- --Builds on Company's Strong Legacy and Commitment in Virology
--Enhances Company's Broad HCV Portfolio with Addition of INX-189, a potent NS5B Nucleotide
Bristol-Myers Squibb Company and Inhibitex, Inc. announced today that the companies have signed a definitive agreement under which Bristol-Myers Squibb will acquire Inhibitex for $26.00 per share in cash pursuant to a cash tender offer and second step merger. The transaction, with an aggregate purchase price of approximately $2.5 billion, has been approved by the boards of directors of both companies. The board of directors of Inhibitex has agreed to recommend that Inhibitex's shareholders tender their shares in the tender offer. In addition, shareholders with beneficial ownership of approximately 17% of Inhibitex's common stock have entered into agreements with Bristol-Myers Squibb to support the transaction and to tender their shares in the tender offer.
Inhibitex is a clinical-stage biopharmaceutical company dedicated to the development of innovative products that can treat or prevent serious infections, whose primary focus is on the development of nucleotide/nucleoside analogs for the treatment of hepatitis C virus (HCV). Its lead HCV asset is INX-189, an oral nucleotide polymerase (NS5B) inhibitor in Phase II development that has exhibited potent antiviral activity, a high barrier to resistance and pan-genotypic coverage.
Nucleotides/nucleosides are emerging as an important class of antivirals that may play a critical role as the backbone of future direct-acting antiviral-only combination approaches to HCV treatment.
"The acquisition of Inhibitex builds on Bristol-Myers Squibb's long history of discovering, developing and delivering innovative new medicines in virology and enriches our portfolio of investigational medicines for hepatitis C," said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. "There is significant unmet medical need in hepatitis C. This acquisition represents an important investment in the long-term growth of the company."
"This transaction puts INX-189 and the Company's other infectious disease assets in the hands of an organization that can more optimally develop them and which believes as strongly as we do in INX-189's potential in the treatment of chronic HCV," said Russell Plumb, President and Chief Executive Officer of Inhibitex. "Bristol-Myers Squibb's expertise in antiviral drug development, and its existing complementary portfolio, will assure that the potential of INX-189 is realized as part of future oral combination therapies for millions of patients in need around the world."
"Bristol-Myers Squibb continues to drive advances in the field of hepatitis C research and development through internal development and selective partnerships," said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer and president, R&D, Bristol-Myers Squibb. "The addition of Inhibitex's nucleotide polymerase inhibitor to our own promising portfolio, which includes other direct-acting antivirals, brings additional options to develop all-oral regimens with better cure rates, shorter duration of therapy and lower toxicity than the current standard of care."
The transaction is expected to be dilutive to earnings for Bristol-Myers Squibb through 2016, with an expected impact on earnings per share of approximately .04 in 2012 and approximately .05 in 2013.
Under the terms of the definitive agreement, Bristol-Myers Squibb will commence a cash tender offer to purchase all of the outstanding shares of Inhibitex's common stock for $26.00 per share. The closing of the tender offer is subject to customary terms and conditions, including the tender of a number of shares that constitutes at least a majority of Inhibitex's outstanding shares of common stock (on a fully diluted basis) and expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. The agreement also provides for the parties to effect, subject to customary conditions, a merger to be completed following the completion of the tender offer which would result in all shares not tendered in the tender offer being converted into the right to receive $26.00 per share in cash. The merger agreement contains a provision under which Inhibitex has agreed not to solicit any competing offers for the company. Bristol-Myers Squibb will finance the acquisition from its existing cash resources. The companies expect the tender offer to close approximately thirty days after commencement of the tender offer.
Citi is serving as financial advisor to Bristol-Myers Squibb in connection with the acquisition and Kirkland & Ellis LLP is its legal advisor. Credit Suisse Securities (USA) LLC is serving as financial advisor to Inhibitex in connection with the acquisition and Dechert LLP is its legal advisor.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews .
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company's clinical-stage pipeline includes three Phase 2 development programs: INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections, FV-100, a nucleoside inhibitor in development for the reduction of shingles-associated pain, and Aurexis, a humanized monoclonal antibody in development for the treatment of serious S. aureus bloodstream infections. The Company also has other HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of a staphylococcal vaccine, which is currently being evaluated in a Phase 1/2 clinical trial. For additional information about the Company, please visit www.inhibitex.com . Inhibitex(R), MSCRAMM(R) andAurexis(R) are registered trademarks of Inhibitex, Inc.
NEW YORK & PRINCETON, N.J. & ATLANTA, Jan 07, 2012 (BUSINESS WIRE) -- --Builds on Company's Strong Legacy and Commitment in Virology
--Enhances Company's Broad HCV Portfolio with Addition of INX-189, a potent NS5B Nucleotide
Bristol-Myers Squibb Company and Inhibitex, Inc. announced today that the companies have signed a definitive agreement under which Bristol-Myers Squibb will acquire Inhibitex for $26.00 per share in cash pursuant to a cash tender offer and second step merger. The transaction, with an aggregate purchase price of approximately $2.5 billion, has been approved by the boards of directors of both companies. The board of directors of Inhibitex has agreed to recommend that Inhibitex's shareholders tender their shares in the tender offer. In addition, shareholders with beneficial ownership of approximately 17% of Inhibitex's common stock have entered into agreements with Bristol-Myers Squibb to support the transaction and to tender their shares in the tender offer.
Inhibitex is a clinical-stage biopharmaceutical company dedicated to the development of innovative products that can treat or prevent serious infections, whose primary focus is on the development of nucleotide/nucleoside analogs for the treatment of hepatitis C virus (HCV). Its lead HCV asset is INX-189, an oral nucleotide polymerase (NS5B) inhibitor in Phase II development that has exhibited potent antiviral activity, a high barrier to resistance and pan-genotypic coverage.
Nucleotides/nucleosides are emerging as an important class of antivirals that may play a critical role as the backbone of future direct-acting antiviral-only combination approaches to HCV treatment.
"The acquisition of Inhibitex builds on Bristol-Myers Squibb's long history of discovering, developing and delivering innovative new medicines in virology and enriches our portfolio of investigational medicines for hepatitis C," said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. "There is significant unmet medical need in hepatitis C. This acquisition represents an important investment in the long-term growth of the company."
"This transaction puts INX-189 and the Company's other infectious disease assets in the hands of an organization that can more optimally develop them and which believes as strongly as we do in INX-189's potential in the treatment of chronic HCV," said Russell Plumb, President and Chief Executive Officer of Inhibitex. "Bristol-Myers Squibb's expertise in antiviral drug development, and its existing complementary portfolio, will assure that the potential of INX-189 is realized as part of future oral combination therapies for millions of patients in need around the world."
"Bristol-Myers Squibb continues to drive advances in the field of hepatitis C research and development through internal development and selective partnerships," said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer and president, R&D, Bristol-Myers Squibb. "The addition of Inhibitex's nucleotide polymerase inhibitor to our own promising portfolio, which includes other direct-acting antivirals, brings additional options to develop all-oral regimens with better cure rates, shorter duration of therapy and lower toxicity than the current standard of care."
The transaction is expected to be dilutive to earnings for Bristol-Myers Squibb through 2016, with an expected impact on earnings per share of approximately .04 in 2012 and approximately .05 in 2013.
Under the terms of the definitive agreement, Bristol-Myers Squibb will commence a cash tender offer to purchase all of the outstanding shares of Inhibitex's common stock for $26.00 per share. The closing of the tender offer is subject to customary terms and conditions, including the tender of a number of shares that constitutes at least a majority of Inhibitex's outstanding shares of common stock (on a fully diluted basis) and expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. The agreement also provides for the parties to effect, subject to customary conditions, a merger to be completed following the completion of the tender offer which would result in all shares not tendered in the tender offer being converted into the right to receive $26.00 per share in cash. The merger agreement contains a provision under which Inhibitex has agreed not to solicit any competing offers for the company. Bristol-Myers Squibb will finance the acquisition from its existing cash resources. The companies expect the tender offer to close approximately thirty days after commencement of the tender offer.
Citi is serving as financial advisor to Bristol-Myers Squibb in connection with the acquisition and Kirkland & Ellis LLP is its legal advisor. Credit Suisse Securities (USA) LLC is serving as financial advisor to Inhibitex in connection with the acquisition and Dechert LLP is its legal advisor.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews .
About Inhibitex
Inhibitex, Inc. is a biopharmaceutical company focused on developing products to prevent and treat serious infectious diseases. The Company's clinical-stage pipeline includes three Phase 2 development programs: INX-189, a nucleotide polymerase inhibitor in development for the treatment of chronic hepatitis C infections, FV-100, a nucleoside inhibitor in development for the reduction of shingles-associated pain, and Aurexis, a humanized monoclonal antibody in development for the treatment of serious S. aureus bloodstream infections. The Company also has other HCV nucleotide polymerase inhibitors in preclinical development and has licensed the use of its proprietary MSCRAMM(R) protein platform to Pfizer for the development of a staphylococcal vaccine, which is currently being evaluated in a Phase 1/2 clinical trial. For additional information about the Company, please visit www.inhibitex.com . Inhibitex(R), MSCRAMM(R) andAurexis(R) are registered trademarks of Inhibitex, Inc.
Thursday, January 5, 2012
UK researchers produce robust HCV-specific T-cell responses to HCV virus in healthy human subjects...
From Doctors Lounge.com According to a study just published in the journal 'Science Translational Medicine', researchers at the University of Oxford have induced HCV-specific T-cell responses against genotype 1a and 3a hepatitis C viruses using an adenovirus-based vaccine in healthy human subjects. I've been around virology enough to be severely jaded when it comes to effective vaccines for highly-replicative, error-prone viruses, but hope springs eternal despite myself.
Novel Hepatitis C Vaccine Induces T Cell Responses. In first trial of an adenovirus-based vaccine for HCV, vectors well tolerated and highly immunogenic.
Adenovirus-based vaccines can generate strong, broad, long-lasting, and functional T cell responses against hepatitis C virus in healthy people, according to a study published in the Jan. 4 issue of Science Translational Medicine.
THURSDAY, Jan. 5 (HealthDay News) -- Adenovirus-based vaccines can generate strong, broad, long-lasting, and functional T cell responses against hepatitis C virus (HCV) in healthy people, according to a study published in the Jan. 4 issue of Science Translational Medicine.
Eleanor Barnes, M.D., of the University of Oxford in the United Kingdom, and colleagues used a recombinant adenoviral vector strategy in a phase 1 trial of an HCV vaccine in healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes (human adenovirus 6 and chimpanzee adenovirus 3). The researchers found that both of the vectors primed T cell responses against HCV proteins. The T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells included both CD4+ and CD8+ T cell subsets and secreted interleukin-2, interferon-gamma, and tumor necrosis factor-alpha.
The T cell response could be sustained for at least a year after boosting with the heterologous adenoviral vector. Examination using major histocompatibility complex peptide tetramers revealed T cells (central and effector) that retained polyfunctionality and proliferative capacity.
"These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV," the authors write.
Novel Hepatitis C Vaccine Induces T Cell Responses. In first trial of an adenovirus-based vaccine for HCV, vectors well tolerated and highly immunogenic.
Adenovirus-based vaccines can generate strong, broad, long-lasting, and functional T cell responses against hepatitis C virus in healthy people, according to a study published in the Jan. 4 issue of Science Translational Medicine.
THURSDAY, Jan. 5 (HealthDay News) -- Adenovirus-based vaccines can generate strong, broad, long-lasting, and functional T cell responses against hepatitis C virus (HCV) in healthy people, according to a study published in the Jan. 4 issue of Science Translational Medicine.
Eleanor Barnes, M.D., of the University of Oxford in the United Kingdom, and colleagues used a recombinant adenoviral vector strategy in a phase 1 trial of an HCV vaccine in healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes (human adenovirus 6 and chimpanzee adenovirus 3). The researchers found that both of the vectors primed T cell responses against HCV proteins. The T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells included both CD4+ and CD8+ T cell subsets and secreted interleukin-2, interferon-gamma, and tumor necrosis factor-alpha.
The T cell response could be sustained for at least a year after boosting with the heterologous adenoviral vector. Examination using major histocompatibility complex peptide tetramers revealed T cells (central and effector) that retained polyfunctionality and proliferative capacity.
"These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV," the authors write.
Wednesday, January 4, 2012
Inhibitex shares roiled by rumors...
An article appearing today on The Street.com by Adam Feuerstein. The power of rumor realized as investors speculate on biotech analyst Rachel McMinn's comments regarding the safety profile for Inhibitex's polymerase inhibitor INX-189. In December, Pharmasset amended it's clinical trials for PSI-938, a similar drug to INX-189, due to liver toxicity signals
ALPHARETTA, Ga. (TheStreet) -- Shares of hepatitis C drug developer Inhibitex(INHX_) whipsawed Wednesday on a mash of rumors, analyst chatter and speculation all tied to the safety of the company's lead drug INX-189.
With an important safety check on INX-189 expected this month or next, investors are clearly twitchy nervous -- more so since Pharmasset(VRUS_) shut down clinical work on a similar hepatitis C drug last month due to liver toxicity.
Inhibitex shares lost as much as 16% of their value Wednesday on no apparent news, which naturally sent investor searching for an explanation. This is on top of an 8% drop in the stock on Tuesday.
At first, the Inhibitex weakness was attributed to the rival Achillion Pharmaceuticals(ACHN_) receiving FDA fast-track status for its hepatitis C drug. This explanation was quickly discarded for its utter stupidity.
Inhibitex, speaking through multiple sell-side analysts defending the stock, said nothing materially had changed with the INX-189 study. The stock began to recover.
Most likely, Inhibitex sold off because of cautious and unpublished comments made by Bank of America/Merrill Lynch biotech analyst Rachel McMinn to her investor clients during a series of marketing meetings this week. McMinn is the axe on hepatitis C drug stocks so her comments carry a lot of weight.
Speaking about the upcoming data on INX-189, McMinn reportedly told her Wall Street clients that while the risk-reward in Inhibitex shares is still positive, the stock has dramatic downside if safety issues crop up.
"Preclinical toxicity [with INX-189] is there but no one knows if it will translate into a clinical concern," McMinn told her clients, according to an email sent by Bank of America brokers to investors earlier today. The email was sent to investors in an attempt to clarify McMinn's views on Inhibitex and the outlook on INX-189.
Inhibitex is conducting a phase Ib study that is evaluating a 200 mg dose of INX-189 plus ribavirin over 7 days in patients with genotype 1 hepatitis C. Another arm of the study evaluates 200 mgs of INX-189 plus interferon and ribavirin for 28 days in genotype 2/3 hepatitis C patients.
FDA 'Fast Tracks' Achillion's once-daily pan-genotypic protease inhibitor ACH-1625...
From Hartford Business.com
Federal drug regulators have "fast tracked'' one of the drugs that New Haven's Achillion Pharmaceuticals Inc. has developed to treat chronic sufferers of hepatitis C, hastening its potential commercial availability.
The U.S. Food and Drug Administration (FDA) cleared ACH-1625, a once-a-day dosage, for the chronic liver disease currently being evaluated in a Phase 2 clinical trial.
The 15-year-old fast track designation means the drug has shown better safety and tolerability, more convenient dosing and the potential to treat a wider universe of patients than existing treatments, Achillion CEO Michael Kishbauch said Wednesday.
It allows regulators to review Achillion's ACH-1625 data as it becomes available, rather than waiting for it all to be collected and bundled into a single, bulky application.
Doing it this way, authorities say, also allows for more frequent interaction between Achillion and FDA investigators, which could shorten the development and review period
Liver International review article - "Barriers to Hepatitis C Treatment"
(Review article authored by Christopher E. McGowan and Michael W. Fried from the Division of Gastroenterology and Hepatology, UNC Liver Center, University of North Carolina at Chapel Hill Chapel Hill, NC, US. Click on the link attached for a PDF copy of the article)
Abstract:
"Despite the availability of highly effective therapy for hepatitis C virus (HCV) infection, few patients receive treatment. Barriers arising at multiple levels, from diagnosis to specialist referral, may impede the delivery of hepatitis C care. At the patient level, lack of awareness, fear of side effects, poor adherence and comorbid conditions may prevent treatment. For providers,limited knowledge, lack of availability and communication difficulties may be problematic. At the government and payer level, a lack of promotion, surveillance and funding may interfere. Each of these barriers needs to be addressed if wider implementation of antiviral therapy is to be achieved."
Monday, January 2, 2012
New research unveils how HCV 'hijacks' human hepatocyte microRNA...
Interesting press release about a research collaboration between the University of North Carolina at Chapel Hill and the University of Colorado regarding the role of microRNAs (specifically, miR-122) within the human hepatocyte and how the Hepatitis C virus 'hijacks' this small RNA molecule as an integral part of its survival strategy.
Viral diseases are still one of the biggest challenges to medical science. Thanks to thousands of years of co-evolution with humans, their ability to harness the biology of their human hosts to survive and thrive makes them very difficult to target with medical treatment.
Scientists at the University of North Carolina at Chapel Hill, working with colleagues from the University of Colorado, have shown for the first time how a small RNA molecule that regulates gene expression in human liver cells has been hijacked by the hepatitis C virus to ensure its own survival – helping medical scientists understand why a new antiviral drug appears to be effective against the virus.
MicroRNAs are involved in regulating the expression of genes in cells, usually by blocking the production of key proteins or by destabilizing the messenger RNAs that encode the cell's proteins as it grows and divides. Normally they act by downregulating gene expression. The research team found that the binding of a prominent microRNA in liver cells, called miR-122, to the viral RNA results in its stabilization, promoting efficient replication of the virus genome in the liver and supporting the virus' lifecycle.
"The hepatitis C virus has done two very interesting things with miR-122," says Stanley M. Lemon, MD, professor of medicine and microbiology and immunology and a member of UNC Lineberger Comprehensive Cancer Center and the Center for Translational Immunology.
"First, it has evolved a unique relationship with a key regulator, since miR-122 represents about half of all microRNAs present in the liver. Second, the virus has usurped a process that usually downregulates gene expression to upregulate the stability of its RNA and expression of viral proteins needed for its lifecycle. It's a classic example of how viruses subvert normally beneficial functions of the cell to their own nefarious purposes."
Work by Dr. Lemon and his colleagues in 2005 helped to demonstrate that miR-122 was required for hepatitis C to replicate itself, but the mechanism was not understood. Now the UNC research team has shown how it works, which helps to explain how a new experimental antiviral drug target the virus. The drug, called an "antagomer", binds to miR-122 and sequesters it in the liver and thus destabilizes the viral genome, accelerating its degradation in the liver. Results of the most recent study are published online this week in the journal Proceedings of the National Academy of Sciences.
Hepatitis C is a continuing public health problem, which is difficult to measure because symptoms occur months to years after infection. The Centers for Disease Control and Prevention estimates as many as 4 million people in the United States may be persistently infected with hepatitis C virus, and most do not know they are infected. More than a third of those who are long-term carriers may develop chronic liver disease or liver cancer, a deadly form of cancer that is becoming increasingly common due to the spread of this virus.
Provided by University of North Carolina
Viral diseases are still one of the biggest challenges to medical science. Thanks to thousands of years of co-evolution with humans, their ability to harness the biology of their human hosts to survive and thrive makes them very difficult to target with medical treatment.
Scientists at the University of North Carolina at Chapel Hill, working with colleagues from the University of Colorado, have shown for the first time how a small RNA molecule that regulates gene expression in human liver cells has been hijacked by the hepatitis C virus to ensure its own survival – helping medical scientists understand why a new antiviral drug appears to be effective against the virus.
MicroRNAs are involved in regulating the expression of genes in cells, usually by blocking the production of key proteins or by destabilizing the messenger RNAs that encode the cell's proteins as it grows and divides. Normally they act by downregulating gene expression. The research team found that the binding of a prominent microRNA in liver cells, called miR-122, to the viral RNA results in its stabilization, promoting efficient replication of the virus genome in the liver and supporting the virus' lifecycle.
"The hepatitis C virus has done two very interesting things with miR-122," says Stanley M. Lemon, MD, professor of medicine and microbiology and immunology and a member of UNC Lineberger Comprehensive Cancer Center and the Center for Translational Immunology.
"First, it has evolved a unique relationship with a key regulator, since miR-122 represents about half of all microRNAs present in the liver. Second, the virus has usurped a process that usually downregulates gene expression to upregulate the stability of its RNA and expression of viral proteins needed for its lifecycle. It's a classic example of how viruses subvert normally beneficial functions of the cell to their own nefarious purposes."
Work by Dr. Lemon and his colleagues in 2005 helped to demonstrate that miR-122 was required for hepatitis C to replicate itself, but the mechanism was not understood. Now the UNC research team has shown how it works, which helps to explain how a new experimental antiviral drug target the virus. The drug, called an "antagomer", binds to miR-122 and sequesters it in the liver and thus destabilizes the viral genome, accelerating its degradation in the liver. Results of the most recent study are published online this week in the journal Proceedings of the National Academy of Sciences.
Hepatitis C is a continuing public health problem, which is difficult to measure because symptoms occur months to years after infection. The Centers for Disease Control and Prevention estimates as many as 4 million people in the United States may be persistently infected with hepatitis C virus, and most do not know they are infected. More than a third of those who are long-term carriers may develop chronic liver disease or liver cancer, a deadly form of cancer that is becoming increasingly common due to the spread of this virus.
Provided by University of North Carolina
NovaTarg preps for 2012 IND filing for hepatitis C drug candidate...
NC-bansed NovaTarq secured a loan and other grants to prep it's AMPK-based research with potential applications in addressing liver diseases, diabetes and cancer. The hope to file an IND in 2012 for a Hepatitis C compound.
NovaTarg preps for 2012 IND filing for hepatitis C drug candidate
Drug discovery startup NovaTarg is ramping up preclinical research in preparation of an expected investigational new drug application filing for the company’s first drug candidate — a new hepatitis C treatment .
The Research Triangle Park, North Carolina-based company now has a $30,000 loan from the North Carolina Biotechnology Center to help its efforts. The Biotech Center’s company inception loans are intended to help biotech companies bridge the early stage funding gap that many life science startups face. The program supports business development activities and does not fund scientific or technical development work. The loan positions NovaTarg to raise additional outside funding to support advancement of its therapies into clinical trials.
“NovaTarg is making great strides toward the identification of our first drug candidate for the treatment of hepatitis C and other liver-associated diseases,” company founder and CEO Kenneth Batchelor said in a statement. “We look forward to using the (company inception loan) to fund key aspects of this discovery effort.”
NovaTarg’s research focuses on activating AMPK, an enzyme that regulates how cells use energy. The company says that its research with AMPK has applications in addressing liver diseases, diabetes and cancer.
NovaTarg’s drug pipeline plans call for work on preclinical safety, pharmacokinetics and formulation in 2012, leading up to an IND filing. The company expects its first drug candidate to begin clinical trials in 2013.
NovaTarg was founded in 2009 by Batchelor, a pharmaceutical industry veteran who rose to become senior vice president for drug discovery at GlaxoSmithKline (NYSE:GSK). NovaTarg has been financially supported by grants. In addition to National Institutes of Health grants, the company also received a total of $223, 516 in grant money from the Therapeutic Discovery Project. The federal program allocated $1 billion in tax credits and grants, capped at $5 million per applicant, for projects that show potential to produce new therapies.
NovaTarg preps for 2012 IND filing for hepatitis C drug candidate
Drug discovery startup NovaTarg is ramping up preclinical research in preparation of an expected investigational new drug application filing for the company’s first drug candidate — a new hepatitis C treatment .
The Research Triangle Park, North Carolina-based company now has a $30,000 loan from the North Carolina Biotechnology Center to help its efforts. The Biotech Center’s company inception loans are intended to help biotech companies bridge the early stage funding gap that many life science startups face. The program supports business development activities and does not fund scientific or technical development work. The loan positions NovaTarg to raise additional outside funding to support advancement of its therapies into clinical trials.
“NovaTarg is making great strides toward the identification of our first drug candidate for the treatment of hepatitis C and other liver-associated diseases,” company founder and CEO Kenneth Batchelor said in a statement. “We look forward to using the (company inception loan) to fund key aspects of this discovery effort.”
NovaTarg’s research focuses on activating AMPK, an enzyme that regulates how cells use energy. The company says that its research with AMPK has applications in addressing liver diseases, diabetes and cancer.
NovaTarg’s drug pipeline plans call for work on preclinical safety, pharmacokinetics and formulation in 2012, leading up to an IND filing. The company expects its first drug candidate to begin clinical trials in 2013.
NovaTarg was founded in 2009 by Batchelor, a pharmaceutical industry veteran who rose to become senior vice president for drug discovery at GlaxoSmithKline (NYSE:GSK). NovaTarg has been financially supported by grants. In addition to National Institutes of Health grants, the company also received a total of $223, 516 in grant money from the Therapeutic Discovery Project. The federal program allocated $1 billion in tax credits and grants, capped at $5 million per applicant, for projects that show potential to produce new therapies.
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