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Week Ending: November 10 th , 2007
Alan Franciscus
Editor-in-Chief
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This Issue:
November 3rd, 2007
Here's how hepatitis C virus evades the body's cell defences
http://in.news.yahoo.com
By ANI
London, November 3 (ANI): University of Birmingham researchers have discovered that the potentially-fatal hepatitis C virus evades the body's natural defences by slipping directly from cell to cell, suggesting that antibody-based treatments aimed at interrupting the virus' progression may not work as well as hoped.
While making a presentation at a Glasgow conference, the researchers said that their finding might help explain why the virus spreads rapidly in some patients.
Viruses generally enter a cell, replicate themselves, and burst out of the cell with large numbers of copies to infect another cell in the same manner.
However, some viruses can move directly between cells. "Cell to cell transmission" allows them to bypass some of the body's most potent defence systems as antibodies can only attack outside the cell.
Scientists have so far believed that the Hepatitis C virus does not have the ability to move directly between cells, but this has been disproved by the latest study that involved liver tumour cells infected with the virus.
"This is probably why it has been so tricky to tackle. Finding that Hep C uses multiple mechanisms for spreading around the body was not great news, but this discovery will allow those of us working in this area to move ahead with a better understanding of the virus," the BBC quoted Dr Jennifer Timpe, who presented the research to the International Symposium on Hepatitis C Virus in Glasgow, as saying.
"We will have to up our game and find other ways of tackling this relentless virus," she added.
The British Liver Trust has hailed Birmingham researchers' finding as a positive result for treatment solutions.
"Gaining a better understanding of the virus will certainly go some way into the development of treatment for hepatitis C patients - something which is desperately needed. At the moment approximately one in five people with a chronic infection of hepatitis C develop severe liver damage which can lead to liver cancer or liver failure and the need for liver transplantation," he said.
"These results indicate to a positive result for treatment solutions," he added. (ANI)
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November 4th, 2007
Gilead Reveals Phase I Data For GS 9190, An Experimental Compound For The Treatment Of Chronic Hepatitis C - Update [GILD]
http://www.rttnews.com
11/4/2007 9:29:41 PM Sunday, biopharmaceutical company Gilead Sciences, Inc. (GILD) announced preliminary clinical data from an ongoing Phase I study of the drug, GS 9190, for treating infection with the chronic hepatitis C virus at the annual meeting of the American Association for the Study of Liver Diseases at Boston, Massachusetts.
The Foster City, California headquartered company said that GS 9190 is being evaluated in a two-part Phase I study. In the first part of the study (Part A), a single dose of GS 9190 demonstrated encouraging pharmacokinetics and antiviral activity.
The second, multiple dose part of the study (Part B) is designed to enroll 60 HCV infected patients in total, and assess the safety, tolerability, pharmacokinetics and antiviral activity of ascending doses of GS 9190, once or twice daily, for eight days.
The company said that the Phase I study is an ongoing dose-escalation, randomized, double blind, placebo-controlled Phase I clinical trial among treatment-naïve patients infected with HCV genotype 1. Key outcome measures of the study include antiviral activity, pharmacokinetics and safety and tolerability.
Part A of the study evaluated escalating single doses of GS 9190 compared to placebo in five successive cohorts: 40 mg, 120 mg, 240 mg, 240 mg and 480 mg. All single doses of GS 9190 demonstrated antiviral activity. The compound showed greatest effect 24 hours after administration.
Gilead said single doses of GS 9190 were well tolerated. There were no serious or treatment-limiting adverse events. All adverse events recorded were mild, with the exception of one moderate headache.
The company said on the basis of findings observed in Part A, Part B of the study was commenced to study multiple doses, administered over a period of eight days, in four successive cohorts: 40 mg BID, 120 mg BID, 240 mg QD and 240 mg BID. Twice-daily 40 mg and 120 mg doses of GS 9190 achieved a sustained antiviral effect during eight days of treatment.
Included in the study design was an electrocardiographic assessment of QT duration while on drug - a standard test for cardiovascular safety. In the second multiple dose cohort, a possible but not confirmed QT elongation was observed. The company said it has therefore initiated a specific QT study, now underway, in healthy volunteers to further evaluate this finding. The study is expected to conclude before year-end 2007.
Gilead said pending resolution of this safety concern, these encouraging preliminary Phase I trial data support further evaluation of GS 9190 in HCV-infected patients.
GILD closed Friday's regular trading session at $46.91.
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Roche Issues Hepatitis Drug Data
http://www.thestreet.com/
By Elizabeth Trotta
Staff Reporter
Roche said Friday that in a phase IIa study a triple-drug combination for treatment of hepatitis C showed a robust virological response and subsequently will proceed to a phase IIb study.
Presenting results at the American Association of the Study of Liver Diseases (AASLD) meeting in Boston, the Swiss drugmaker said its investigational hepatitis C drug R1626 showed promising antiviral activity in the phase IIa trial when given with Pegasys (peginterferon alfa-2a) and Copegus. The aforementioned Roche drugs are used together to treat adults with chronic hepatitis C whose liver still works normally and who haven't been previously treated with an interferon alpha.
After four weeks of treatment with the three-drug combination, the virus couldn't be detected in 81% of patients with a mean decrease in viral load of 5.2 log10 from the baseline, and Roche said most adverse events were mild to moderate.
Also, no resistance to R1626 was identified following intensive testing for either two weeks of treatment with R1626 as monotherapy or in patients treated with R1626 for four weeks in combination with the standard of care.
The phase IIb study, called POLI 1, which will further investigate R1626 in combination with standard or lower dose of Pegasys and standard dose of Copegus, is now open and enrolling patients in eight countries, including the U.S.
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Treatment With PEGASYS(R)/COPEGUS(TM) Provides Hope For Hepatitis C Patients Whose Infection Did Not Initially Respond To Peg-Intron(R)/Ribavirin
http://www.medicalnewstoday.com
Roche announced final results from the REPEAT study, which demonstrated that treatment with once-weekly PEGASYS(R) (peginterferon alfa-2a) and daily COPEGUS(TM) (ribavirin) for 72 weeks is a promising treatment option for patients whose infection did not respond to previous treatment with another pegylated interferon (Peg- Intron(R), peginterferon alfa-2b) and ribavirin. Further, the results showed that response at 12 weeks was a powerful predictor of the eventual outcome: the majority of patients with undetectable virus at 12 weeks went on to achieve a sustained virological response (SVR) after 72 weeks of treatment, while few patients with detectable virus at 12 weeks achieved SVR. These data were presented in an oral session at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held in Boston, Nov. 2-6.
"One of the greatest areas of need in hepatitis C today is to find solutions for patients who have not seen treatment success with an initial course of therapy. REPEAT is an important study which adds significantly to our knowledge about how to manage these patients, demonstrating that extending treatment with PEGASYS and COPEGUS is a promising option," said Donald Jensen, M.D., Professor of Medicine and Director of the Center for Liver Diseases at the University of Chicago Hospital in Chicago, and lead investigator in REPEAT. "A significant finding from REPEAT is confirmation of the reliability of using a patient's response at 12 weeks as a predictor of treatment success, even in patients with cirrhosis. This means that patients who achieve undetectable virus at 12 weeks can continue treatment with a good likelihood of success. It also means that clinicians can confidently discontinue treatment in patients who do not achieve an early response."
More About the REPEAT Study
Enrolling 950 patients from Europe, North America and Latin America, REPEAT (REtreatment with PEgasys in pATients Not Responding to Peg-Intron Therapy) was designed to explore whether intensified treatment with a higher fixed-dose induction of PEGASYS in combination with COPEGUS and/or longer treatment duration may increase treatment success rates in patients who didn't respond to at least twelve weeks of Peg-Intron/ribavirin combination therapy. Patients were randomized 2:1:1:2 to one of four regimens:
- Patients in arms A (n=318) and B (n=158) received PEGASYS 360 mcg/week for 12 weeks, followed by 180 mcg/week for a further 60 or 36 weeks, respectively
- Patients in arms C (n=158) and D (n=316) received PEGASYS 180 mcg/week for 72 or 48 weeks, respectively
- All patients received COPEGUS (1,000/1,200 mg/day) in combination with PEGASYS
Results showed:
- The primary endpoint was met: SVR, defined by undetectable hepatitis C virus RNA in the blood six months after the end of treatment, was significantly higher for arm A (16 percent) compared to arm D (nine percent)
- A pooled analysis of the 72-week arms vs. the 48-week arms showed that 72 weeks of treatment had the biggest impact on success of treatment, with a doubling of SVR rate compared to 48 weeks (16 percent vs. eight percent). A pooled analysis of the induction dose arms vs. standard dose arms showed that treatment with higher fixed-dose induction for this difficult-to-treat patient population did not provide significant additional benefit
- Response at 12 weeks was a strong predictor of successful treatment
- Of patients whose virus was undetectable after 12 weeks of therapy, 57 percent in the 72-week arms went on to achieve treatment success (by comparison, among patients who still had detectable virus after 12 weeks, only four percent achieved treatment success)
- The proportion of patients with undetectable virus at 12 weeks was 17 percent
"REPEAT exclusively enrolled patients who had not previously responded to pegylated interferon combination therapy, in this case Peg-Intron and ribavirin," continued Dr. Jensen. "These patients are a more difficult-to- treat group than relapsers and those who did not respond at all to treatment with non-pegylated interferons, either alone or with ribavirin. For this reason, results from REPEAT cannot be meaningfully compared to results from trials with a large proportion of patients who were relapsers or who did not respond to treatment with older interferons."
The incidence and types of adverse events and serious adverse events were generally consistent across all the arms, and the frequency of moderate to severe hematologic effects were broadly similar across all arms. Discontinuations for adverse events and lab abnormalities were higher for extended treatment. Patients with cirrhosis had a somewhat higher incidence of adverse events, premature withdrawals and dose modifications.
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Vertex hepatitis C drug effective in trial
http://www.reuters.com/
(In eighth paragraph, corrects to show virus was eradicated for three months, not six, following treatment)
BOSTON, Nov 2 (Reuters) - Vertex Pharmaceuticals Inc's (VRTX.O: Quote, Profile, Research) experimental hepatitis C drug is more effective than existing treatments and works in half the time, but also causes significantly more side effects.
Data to be presented at the Annual Meeting of the American Association of the Study of Liver Diseases show the drug, telaprevir, in combination with standard treatment, eradicated the hepatitis C virus in more than 60 percent of patients who took it as part of a 24-week treatment.
Eradication of the virus is based on a measure known as sustained viral response, in which the virus remains at below detectable levels.
Typically, not more than 50 percent of patients taking standard treatments see their virus eradicated and the typical length of treatment is 48 weeks.
Hepatitis C is a blood-borne liver disease that can cause chronic liver disease, liver cancer and cirrhosis. It affects about 170 million people worldwide.
In a mid-stage trial conducted in the United States known as PROVE 1, 61 percent of 79 patients who took telaprevir in combination with the standard treatments, pegylated interferon and ribavirin, saw the virus fall to undetectable levels in their blood and remained undetectable six months after treatment was stopped.
But 13 percent of patients discontinued the trial in the first 12 weeks because of side effects. The most common side effect was rash.
In a separate mid-stage trial known as PROVE 2, conducted in Europe, 65 percent of patients who took part in the 24-week treatment regime -- which consisted of 12 weeks of triple therapy followed by 12 weeks of standard treatment -- saw the virus eradicated and stay eradicated after three months.
In the PROVE 1 trial, the relapse rate was 2 percent. In PROVE 2 it was 14 percent. Patients who take standard therapy typically relapse at a rate of 20 percent to 30 percent, Vertex said.
The difference in relapse rate between the two trials stemmed from the fact the PROVE 1 trial results were based only on patients who were least likely to relapse in the first place, based on the rapidity of their initial response to the drug.
In the PROVE 2 trial, which did not just measure patients who saw a quick drop in virus after starting therapy, 14 percent of patients relapsed.
Telaprevir is one of a new class of drugs that inhibits a hepatitis C protease, an enzyme essential for the virus to replicate. Vertex's partner on the drug is Tibotec Pharmaceuticals Ltd, of Cork, Ireland. (Reporting by Toni Clarke, Bill Berkrot).
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November 5th, 2007
HGS announces results of Phase 2B trial of Albuferon for chronic hepatitis C
http://www.eurekalert.org
Albuferon requires half as many injections as standard therapy, and demonstrated at least comparable efficacy, comparable safety and less impairment of quality of life on treatment
ROCKVILLE, Maryland – November 5, 2007 – Human Genome Sciences, Inc. (NASDAQ: HGSI) today announced the final results of a Phase 2b clinical trial of the investigational drug, Albuferon® (albinterferon alfa-2b), in combination with ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C. This Phase 2b study demonstrated that, with half as many injections as Pegasys (peginterferon alfa 2a), Albuferon was just as effective in achieving sustained virologic response (SVR) – an undetectable amount of virus in the blood at 24 weeks following the end of treatment – with comparable safety and less impairment of health-related quality of life on treatment. Albuferon is administered every two weeks, while peginterferon alfa-2a requires administration every week.
The final Phase 2b data are being presented this week at the 58 th AASLD Annual Meeting in Boston. In two additional press releases also issued by HGS today, the Company announced the full presentations at AASLD of quality-of-life data from the Phase 2b trial, and results from the Phase 2 trial of Albuferon in combination with ribavirin in patients with chronic hepatitis C who had not responded to previous interferon-based treatment regimens.
“The final Phase 2b results suggest that the every-two-week dosing regimen of Albuferon halves the number of injections that are required with peginterferon alfa-2a, while providing at least comparable efficacy, comparable safety and the potential for less impairment of quality of life and daily activity,” said Stefan Zeuzem, M.D., Professor of Medicine and Chief, Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany. “We are continuing the evaluation of the 900-mcg and 1200-mcg doses of Albuferon in larger populations in Phase 3 trials. We also conclude that monthly dosing of Albuferon deserves further evaluation.”
In the open-label, multi-center, active-controlled Phase 2b trial, 458 treatment-naive patients with genotype 1 chronic hepatitis C were randomized to four treatment groups: Albuferon 900 mcg every two weeks, Albuferon 1200 mcg every two weeks, Albuferon 1200 mcg every four weeks, and peginterferon alfa-2a 180 mcg once a week. All patients received weight-based oral ribavirin daily. The trial included 48 weeks of treatment, and the primary efficacy endpoint was SVR, defined as undetectable viral load (HCV RNA<10 IU/mL) at 24 weeks following completion of treatment.
“Assuming that the Phase 2 results are confirmed in Phase 3, we believe that Albuferon could become the interferon of choice in combination regimens for the treatment of chronic hepatitis C,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “Both of our Phase 3 trials have completed enrollment ahead of schedule, and we expect to have Phase 3 data available by spring 2009 to support the filing of global marketing authorization applications by fall 2009.”
Key Findings from the Phase 2b Study
Albuferon requires half the number of injections as peginterferon alfa-2a, and the final results of the Phase 2b study demonstrated that Albuferon provided at least comparable efficacy and comparable safety vs. peginterferon alfa-2a (ITT analysis), with less impairment of quality of life on treatment and fewer lost days of work .
The final Phase 2b results include the following SVR rates and other findings:
Albuferon 900-mcg Every Two Weeks (Albuferon 900 Q2w)
- Based on an intention-to-treat ( ITT) analysis, 58.5% of patients in the Albuferon 900 Q2w treatment group achieved SVR, vs. 57.9% for peginterferon alfa-2a administered every week.
- In heavier patients (>75 kg) who were treatment-adherent, 74.2% of those in the Albuferon 900 Q2w treatment group achie ved SVR , versus 53.3% for peginterferon alfa-2a. Among all treatment-adherent patients in the Albuferon 900 Q2w treatment group , 72.3% achieved SVR, versus 66.7% for peginterferon alfa-2a.
- Based on the SF-36 Health Survey, patients in the Albuferon 900 Q2w treatment group reported less impairment of health-related quality of life, compared with patients in the peginterferon alfa-2a treatment group, as measured by both physical component and mental component SF-36 summary measures at all time-points throughout the 48-week treatment period.
- Significantly fewer working patients in the Albuferon 900 Q2w treatment group reported missing 7 days or more of work during the month prior to their visits at Weeks 12 and 24, vs. the peginterferon alfa-2a group (p<.05; Week 12: 4.2% for Albuferon 900 Q2w vs. 18.1% for peginterferon alfa-2a; Week 24: 5.3% for Albuferon 900 Q2w, vs. 20.3% for peginterferon alfa-2a).
- The rate of discontinuations due to adverse events was 9.3% in the Albuferon 900 Q2w treatment group, vs. 6.1% in the peginterferon alfa-2a group. Adverse events observed were those typically expected with interferon therapy.
Albuferon 1200-mcg Every Two Weeks (Albuferon 1200 Q2w)
- ITT analysis shows that 55.5% of patients in the Albuferon 1200 Q2w treatment group achieved SVR, vs. 57.9% for peginterferon alfa-2a administered every week.
- In heavier patients (>75 kg) who were treatment-adherent, 67.9% of those in the Albuferon 1200 Q2w treatment group achie ved SVR, versus 53.3% for peginterferon alfa-2a every week.
- Among all treatment-adherent patients in the Albuferon 1200 Q2w treatment group , 70.6% achieved SVR , versus 66.7% for peginterferon alfa-2a.
- ITT analysis shows that the Albuferon 1200 Q2w treatment group exhibited a robust early antiviral response (reduction in hepatitis C RNA viral load to below the level of quantitation): 74.5% for Albuferon 1200 Q2w at Week 12, vs. 65.8% for peginterferon alfa-2a. The Albuferon 1200 Q2w treatment group also had the most rapid time to HCV RNA negativity.
- The rate of discontinuations due to adverse events was 18.2% in the Albuferon 1200 Q2w treatment group, vs. 6.1% in the peginterferon alfa-2a group. Adverse events observed were those typically expected with interferon therapy. Dose reductions were attempted in only 24.4% of Albuferon subjects prior to discontinuation, versus 42.9% for peginterferon alfa-2a. Adverse events observed were those typically expected with interferon therapy.
- “In the Albuferon Phase 3 trials, we are strongly encouraging titration of dose where necessary to increase tolerability, reduce the rate of discontinuations, and maximize the therapeutic benefit of the robust early antiviral response offered by the 1200-microgram dose on a two-week administration schedule,” said Dr. Stump.
Albuferon 1200-mcg Monthly (Albuferon 1200 Q4w)
- ITT analysis shows that 50.9% of patients in the Albuferon 1200 Q4w treatment group achieved SVR, vs. 57.9% for peginterferon alfa-2a administered every week.
- In heavier patients (>75 kg) who were treatment-adherent, 61.0% of those in the Albuferon 1200 Q4w treatment group achie ved SVR, versus 53.3% for peginterferon alfa-2a administered once every week.
- Among all treatment-adherent patients in the Albuferon 1200 Q4w treatment group, 62.0% achieved SVR, versus 66.7% for peginterferon alfa-2a.
- The rate of discontinuations due to adverse events was 12.1% in the Albuferon 1200 Q4w treatment group, vs. 6.1% in the peginterferon alfa-2a group. Adverse events observed were those typically expected with interferon therapy.
- The number of patients experiencing severe hematologic adverse events was significantly lower in the Albuferon 1200 Q4w treatment group (10.3%, vs. 20.2% for peginterferon alfa-2a, p<0.05).
- Higher doses of Albuferon administered every four weeks, in combination with ribavirin, will be explored in a separate Phase 2b trial conducted by Novartis, which is expected to begin by year-end 2007.
###
About Albuferon
Albuferon is a novel long-acting form of interferon alpha created by HGS using its proprietary albumin fusion technology. Albuferon results from the genetic fusion of human albumin and interferon alpha. Human albumin is the most prevalent naturally occurring blood protein in the human circulatory system, persisting in circulation in the body for more than 20 days. Research shows that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the proteins. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a number of cancers.
Albuferon is being developed by HGS and Novartis for the treatment of chronic hepatitis C under a worldwide co-development and commercialization agreement entered into in June 2006. HGS and Novartis will co-commercialize Albuferon in the United States and will share clinical development costs, U.S. commercialization costs and U.S. profits equally. Novartis will be responsible for commercialization in the rest of the world and will pay HGS a royalty on those sales. Clinical development, commercial milestone and other payments to HGS could total as much as $507.5 million, including $132.5 million received to date.
About Hepatitis C
Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). An estimated 170 million people worldwide are infected with the virus, including nearly 4 million people in the United States. When detectable levels of HCV persist in the blood for at least six months, a person is diagnosed with chronic hepatitis C. Hepatitis C virus can cause serious liver disease, leading to cirrhosis, primary liver cancer and even death.
About Human Genome Sciences
The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs.
The HGS clinical development pipeline includes novel drugs to treat hepatitis C, lupus, anthrax disease, cancer and other immune-mediated diseases. The Company’s primary focus is rapid progress toward the commercialization of its two key lead drugs, Albuferon for hepatitis C and LymphoStat-B® (belimumab) for lupus. Phase 3 clinical trials of both drugs are ongoing.
ABthrax™ (raxibacumab) is in late-stage development for the treatment of anthrax disease, and the Company is on track to begin the delivery in 2008 of 20,000 doses of ABthrax to the Strategic National Stockpile under a contract entered into with the U.S. Government in June 2006. Other HGS drugs in clinical development include two TRAIL receptor antibodies for the treatment of cancers.
For more information about HGS, please visit the Company’s web site at www.hgsi.com. To view the AASLD oral presentation reporting results of the Phase 2b clinical trial of Albuferon in combination with ribavirin in treatment-naive patients (Zeuzem, et al), click here. To view the AASLD poster presentation reporting quality of life results from the Phase 2b clinical trial of Albuferon (Pianko, et al), click here. To view the AASLD oral presentation reporting results of the Phase 2 trial of Albuferon in non-responders (Nelson, et al), click here. To view the AASLD poster presentation reporting results of a prospective comparison of commercial fibrosis serum marker panels (Patel, et al), click here. For more information about Albuferon, please visit www.hgsi.com/products/albuferon.html. Health professionals or patients interested in Albuferon clinical trials or other studies involving HGS products may inquire via the “Contact Us” section of the Company’s web site, www.hgsi.com/products/request.html, or by calling (301) 610-5790, extension 3550.
HGS, Human Genome Sciences, ABthrax, Albuferon and LymphoStat-B are trademarks of Human Genome Sciences, Inc.
SafeHarbor Statement
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences’ current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company’s unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company’s ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company’s dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company’s filings with the Securities and Exchange Commission. In addition, the Company will continue to face risks related to animal and human testing, to the manufacture of ABthrax and to FDA concurrence that ABthrax meets the requirements of the ABthrax contract. If the Company is unable to meet the product requirements associated with the ABthrax contract, the U.S. government will not be required to reimburse the Company for the costs incurred or to purchase any ABthrax doses. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today’s date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
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Alliance formed to develop treatments for hepatitis C
http://www.bizjournals.com
Philadelphia Business Journal
by John George Staff Writer
The Bucks County Institute for Hepatitis and Virus Research and BioLeap, a New Hope drug-discovery company, will jointly develop therapeutic compounds to treat hepatitis C.
The alliance combines BioLeap's computational fragment-based drug-design technology with the institute's knowledge of viral diseases.
BioLeap, which describes itself as a lab-less drug-discovery company, relies on computers rather than test tubes to find new drug candidates.
It specializes in computational fragment-based design, which involves using the company's in-house computer cluster and proprietary algorithms to rapidly calculate the potential for small molecular fragments of biological compounds to bind to, and inhibit, targeted proteins.
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Survival In Hepatitis C Virus Patients Prolonged By 24-Week Course Of Interferon-Alpha Therapy
http://www.medicalnewstoday.com
Patients with the hepatitis C virus (HCV) have a risk of frequent recurrence and deterioration of liver function, even after curative treatment for the primary hepatocellular carcinoma (HCC). This unfavorable prognosis is associated with a sustained HCV infection. Thus, both the prevention of HCC recurrence and the preservation of liver function are high priorities when trying to improve the prognosis of patients with HCV-related HCC. Antiviral therapy for chronic hepatitis C (HCV) after treatment for primary HCC is the essential factor required for an improved prognosis.
A research article written by a study group at Japan's Hiroshima University Hospital, published on October 28 in the World Journal of Gastroenterology, suggests the importance of viral eradication. This study group performed a matched case-controlled study and compared 42 patients undergoing a 24-week course of interferon therapy and 42 patients who did not receive any interferon therapy. The purpose of the study was to determine whether a 24-week course of interferon-alpha therapy after curative treatment for HCV-associated HCC could possibly influence tumor recurrence, patient survival, and liver function.
The study group found that the second recurrence rate was significantly lower in patients that underwent interferon therapy as compared to those patients that did not have interferon therapy, although the first recurrence rate in patients with and without interferon therapy did not differ. Additionally, results also indicated that the interferon therapy patients had longer survival periods than the patients who did not have interferon therapy.
The study group also determined that when patients without interferon therapy were compared to patients without any virological response, only the virological responders within the interferon therapy group had a better prognosis with regard to the recurrence, liver function, and survival. Overall, the results indicated it is the sustained virological response that is the most important factor for decreasing the risk of HCC recurrence, including for the second recurrence and for prolonged survival. The state of the virological response improved the prognosis by suppressing the multicentric recurrence, which was related to the sustained hepatic necrosis and inflammation.
The study group also demonstrated that the state of the sustained virological response was responsible for preventing functional liver deterioration, which is related to the underlying HCV-related hepatic damage. Thus, patients with viral elimination are able to survive longer than both the patients without interferon therapy and the patients without virological response following interferon therapy, due to the decreased HCC recurrence and preservation of hepatic function.
After curative treatment of primary HCC, a 24-week course of interferon therapy should be recommended for the purpose of viral eradication.
Article adapted by Medical News Today from original press release.
Reference:
Jeong SC, Aikata H, Katamura Y, Azakami T, Kawaoka T, Saneto H, Uka K, Mori N, Takaki S, Kodama H, Waki K, Imamura M, Shirakawa H, Kawakami Y, Takahashi S, Chayama K.Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma. World J Gastroenterol 2007; 13(40): 5343-5350
Correspondence to:
Hiroshi Aikata, MD, Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
About World Journal of Gastroenterology:
World Journal of Gastroenterology (World J Gastroenterol, WJG), a leading international journal in gastroenterology and hepatology, has an established reputation for publishing fi rst class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection, providing a forum for both clinicians and scientists, and has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by The WJG Press. The publication date is 7th, 14th, 21st, and 28th every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No.30424812, which was founded with a name of China National Journal of New Gastroenterology on October 1, 1995, and renamed as WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: You-De Chang
World Journal of Gastroenterology
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A Winning Soccer Coach Faces a Ruthless Foe
http://www.nytimes.com
By TIMOTHY WILLIAMS
It is a crisp autumn day and the Martin Luther King Jr. High School soccer team is winning again. Their precision passing and stifling defense usually make for one-sided games; until a few weeks ago, the squad was ranked first in the nation.
Many players on Martin Jacobson’s team are immigrants from West Africa and the Caribbean.
On the sideline, a bald man with piercing blue eyes is barking instructions, his hoarse voice so weakened by years of shouting that the sound barely makes it across the field to his players, who are as apt to ignore his words as they are to listen.
“Forward! Forward! Attack! Shoot!” he cries out.
Although the coach said he had a tight bond with his Upper West Side team of mostly immigrant West African, Caribbean and South American teenagers, he acknowledged that there were some things he kept to himself: Primarily that he, Martin Jacobson, age 61, is a former heroin addict who in 1994 learned he had hepatitis C, a potentially fatal and progressive disease. It is now in the third of its four stages.
He is not dying, not really, he says, and even if he were, he wouldn’t want to know — or to have his team have to deal with it.
“I’m not sure what my life expectancy is right now,” he said, as his team prepared for this week’s city playoffs, in which King is favored to win the championship for the 10th time in 12 years. “Am I going to die in six months? Am I going to need a liver transplant, which will change every aspect of my life?”
During his 14-year tenure at King, his teams have won more than 270 games and lost only 14.
But until he quit drugs and alcohol cold turkey in November 1985, the pursuit of a buzz, not soccer, had been the dominant feature of Mr. Jacobson’s life. It is a fact that now embarrasses him.
While he has discussed some of the details of his life with those close to him, many people, including his colleagues at school and his family, have no idea how serious his addiction had become.
He said that now that he is among the best-known youth coaches in New York of any sport — even turning down offers from soccer parents to coach their children privately — he hopes his story can help other people.
“I always felt good,” he said. “I just wanted to feel better.”
During a visit to his doctor on Oct. 25 with his longtime companion, Constance Cosner, 59, Mr. Jacobson said he was unsure how much information he wanted. He said he preferred to rely on vitamin supplements and the power of positive thinking.
“Part of me doesn’t really want to know how many days I have left, or if I’m going to go to Stage 4,” he told the physician, Dr. Robert Mendelsohn. “I’m not going back to interferon, I know that,” he said, referring to a treatment that has helped many hepatitis C patients but has only made him feel more ill. The doctor said Mr. Jacobson was not in any immediate danger of dying or needing a liver transplant, but he wants to do an M.R.I. exam on the liver when the season ends, and a biopsy in the spring.
On the soccer field, as Mr. Jacobson claps and exhorts and hugs his players when he substitutes them in and out of games and dramatically covers his face with his hands in response to their mistakes, no one could guess that the coach, known to most as Jake, is sick — reduced to taking afternoon naps so he can stay awake the rest of the day.
He is a tightly coiled man, even when he is relaxing or telling a joke.
In the past, that intensity has been his undoing: Aside from the heroin addiction, he has been married and divorced three times (a fourth marriage was annulled), been arrested four times, declared bankruptcy twice, fathered six children by five women, and had a bullet graze his head and a drug addict stab him inside a drug den.
Now, he takes 32 pills, mostly vitamin supplements, each day, but says he has neither used illegal drugs nor touched alcohol in 22 years.
“I feel tired much more than I used to — sometimes, I think work keeps me alive,” he said.
Work means being a dean, guidance counselor, athletic director and boys’ and girls’ soccer coach on the campus of Martin Luther King Jr. High, which was among the first schools in the city to be split into smaller schools because of years of low test scores and violence, including the 2002 shooting of two students on campus.
The campus continues to have discipline problems, but Mr. Jacobson has an advantage when dealing with troubled students; he was himself a problem child growing up in Long Beach, on Long Island, during the 1950s.
As a 10-year-old, he was caught by a police officer throwing a rock at a car. But instead of taking him to the police station, the officer brought him to a local recreation center, where he began his lifelong affair with soccer. As much as he loved the sport, he didn’t lose his taste for trouble — he stole a car at 16, got into gang fights, sold marijuana.
After college at Ball State University in Indiana, where he became a star soccer player, he earned a master’s degree in guidance and counseling, but had a hard time staying in one place.
One time, he quit a teaching job in New York, packed his and his wife’s possessions into a Volkswagen bus and drove west, living what he describes as the life of a hippie.
Another time, he left a job in Detroit, and with his wife, their 3-year-old daughter and a German shepherd named Che drove to the Rocky Mountains and lived in a tent near Aspen, Colo., for a month.
LSD provided much of the incentive for the adventure. “I took acid every day,” he said, enough “to kill an elephant.” The trip was even largely financed by LSD, which he had sold in large quantities to assembly line workers at a Ford Motor plant in Detroit.
“I don’t see how any cars came out right,” he said.
After he took a job at Santa Fe High School in New Mexico, he said, his drug use accelerated. He was regularly smoking marijuana, snorting cocaine, dropping acid, taking peyote and quaaludes, and even taking opium anally, because the high was more intense that way.
“He was more interested in getting high than anything else,” said Janet Coffee, his wife at the time. “He could never get enough.”
Still, he managed to be promoted to director of guidance and to start boys’ and girls’ varsity soccer programs.
His drug use, however, eventually doomed his marriage. “She was in love with me,” he said of Ms. Coffee, “and I was in love with drugs.”
In 1981, on his 35th birthday, a girlfriend gave him a present: an injection of Dilaudid, a drug similar to morphine. Within a week, he was hooked.
But when his supply ran out, he switched to black tar heroin, the closest thing to Dilaudid he could find on the streets.
Before long, Mr. Jacobson said, he had exhausted his savings and retirement accounts and refinanced his car loan, and he gradually began dismantling his house for quick cash, selling the custom-made pine cabinets and the kitchen sink. When the electricity was shut off, he and his daughter Lara, of whom he had custody, used candles.
“At lunchtime, I am going down to the projects and scoring dope and shooting up in the school bathroom,” he said.
He wrote bad checks, forged others and shoplifted and returned the same items for cash, among his other hustles. Stints in rehab invariably failed.
Lara, now 36, was spending much of her time alone or hanging out with older children. By the age of 13, she had boyfriends as old as 18, and had begun experimenting with drugs.
“I remember waiting for my dad to come home every night, imagining terrible things happening to him,” she said recently.
And though Mr. Jacobson had taken to sleeping with a .45-caliber revolver under his pillow, he said he had never committed a violent crime to finance his drug use.
Then one day in the early 1980s, Mr. Jacobson said, he and a junkie friend named Geronimo robbed a pharmacy. While Geronimo went inside with a gun, Mr. Jacobson waited in the car — a brown Subaru station wagon.
Mr. Jacobson said he does not know what happened inside the pharmacy, but when Geronimo came out, he had large quantities of pharmaceutical cocaine, codeine, Percodan, Percocet and other drugs.
“We put a mattress against the door and shot drugs for three days,” he said. “We were ready to shoot it out with the cops.”
He was not caught for that crime, but he was eventually arrested for writing bad checks. He was threatened with a long prison term, which he avoided, in part, by becoming a paid informant. The school forced him to resign. Unemployed, he bought heroin with the money the Santa Fe police had given him.
“I was a junkie, I looked like a junkie, I acted like a junkie,” he said. “This wasn’t supposed to happen to me. I was a Jewish kid from a middle-class background on Long Island. It’s unheard of.”
After another arrest, in 1985, for bouncing checks, Mr. Jacobson was ordered out of Santa Rosa, N.M., the small town where he and Lara had moved a few months earlier. They flew to New York. He said he went cold turkey on the flight.
Then, in 1986, after he managed to get a teaching job in East Harlem, two New York City detectives arrested him at the school for an outstanding warrant in New Mexico. He was led out in handcuffs and told that he faced a 30-year prison sentence for forgery and fraud.
He was able to resolve the charges with no jail time, and two years later, he took a job at King High School. In 1994, he took over the boys’ soccer team and embarked on a streak of unprecedented success. But his tenure has been marked by controversy, including accusations of illegal recruiting from rival coaches. Mr. Jacobson was suspended from coaching for a time several years ago, but he was found to be guilty of only poor record keeping, not cheating.
Some of the players who join his team are from Senegal, Mali and Haiti, and they sometimes arrive illegally and without a place to live. He has helped several get housing in city group homes and has been able to help a few get green cards.
He has transformed King into a soccer powerhouse, even though the school has no field. The team practices on the school gym’s basketball courts, and occasionally, the coach and players hop fences to use locked fields.
And although some of his players arrive without speaking English, he said about 75 percent of them graduate within four years, higher than the city average of 50 to 60 percent. Several players have received college scholarships and several play in professional leagues around the world.
“He has this nurturing in him,” said Mansour Ndiaye, 27, one of Mr. Jacobson’s former players, who went on to play on a national championship team at the University of Connecticut and who is studying for his doctorate in sports management. “For a lot of immigrants at M.L.K., without that transition with him, it would have been very tough.”
For now, Mr. Jacobson continues to troll the sidelines, obsessing about not only winning, but playing flawlessly.
He resists the idea that winning has become a replacement addiction for him, though he acknowledges there are similarities.
“When I shot heroin, I got a euphoric feeling,” he said. “And when I win a city championship, I get a euphoric feeling. But now, I wake up the next morning feeling a little better.”
He paused for a moment and added: “The byproduct is different in that I’m helping kids. In addiction, there is no benefit. As a coach, even in losing, I’m still helping kids.”
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Plasma Exchange Effective in Treating Hepatitis C-Associated Cryoglobulinemia: Presented at AASLD
http://www.docguide.com
By Maria Bishop
BOSTON, MA -- November 5, 2007 -- Plasma exchange (plasmapheresis) is an effective therapy for the short-term management of hepatitis C virus (HCV)-associated cryoglobulinemia, according to research presented here at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Cryoglobulinemia is a symptom in 35% of chronic HCV infections, and is generally recognised by "Meltzer's triad" of palpable purpura (spontaneous bleeding into the skin that appears as a rash), joint pain, and muscle pain. Cryoglobulinemia is the presence of a high amount of heavy globulins (eg, Immunoglobulin M) in the bloodstream that thicken upon exposure to cold.
According to Jan C. Hofmann, MD, Staff Physician, Department of Medicine, Division of Immunotherapy, California Pacific Medical Center, San Francisco, California, United States, acute treatment is required for progressive, systemic cryoglobulinemia, which is further characterised by renal dysfunction, cutaneous vasculitis, peripheral neuropathy, or other organ involvement.
In a small, retrospective study, Dr. Hofmann and Robert Gish, MD, Medical Director, Liver Disease Management & Transplant Program, California Pacific Medical Center, examined the medical records of 21 patients diagnosed between January 2005 and May 2007 with moderate to severe HCV-associated cryoglobulinemia and referred to the California Pacific Medical Center for plasmapheresis treatment.
Nineteen of the patients (90%) received a course of inpatient plasma exchange every other day (mean number of treatments 8.4). The other two patients received outpatient plasma exchange 2 to 3 times per week.
Twenty patients (95%) experienced clinical improvement with plasmapheresis, the researchers noted.
Nine of 13 patients with nephrotic-range proteinuria experienced a significant decline in urinary protein and a mean decrease of 45% in serum creatinine. Three of 6 dialysis patients were able to stop dialysis.
Seventeen of 18 patients with elevated rheumatoid factor (RF) had a marked decrease in RF (12 of these normalised their levels). Twelve of thirteen patients with active vasculitic skin lesions demonstrated significant improvement. Six of 7 patients with peripheral neuropathy experienced a slight to moderate improvement in symptoms.
Of the inpatients, several were treated with additional concurrent therapies after plasmapheresis: 8 received low-dose oral or intravenous cyclophosphamide to prevent rebound of immune-complex production; 5 underwent rituximab weekly treatment (4 to 6 doses); 15 started weekly pegylated alfa interferon therapy for up to 4 weeks; and 12 also started daily oral ribavirin.
Some patients, Dr. Hofmann noted, may require maintenance plasmapheresis treatment for persistent, acute cryoglobulinemia.
[Presentation title: Hepatitis C Associated Systemic Cryoglobulinemia: Successful Treatment With Plasma Exchange. Abstract 331]
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Conatus Pharmaceuticals Reports Positive Results of CTS-1027 in Multiple Preclinical Studies of Liver Disease
http://www.earthtimes.org
SAN DIEGO, Nov. 5 /PRNewswire/ -- Conatus Pharmaceuticals Inc. today reported positive preclinical results on its lead compound, CTS-1027 in multiple models of hepatitis, an inflammatory liver disease. The results were presented in a poster session today at the American Association for the Study of Liver Diseases (AASLD) in Boston, MA.
CTS-1027 significantly reduced liver damage following oral administration in four different preclinical models of liver injury. CTS-1027 markedly reduced aminotransferase (ALT) activity and improved survival and liver histology in the TNFalpha/Gln model. CTS-1027 was equally effective dosed at the same time as the insult or post-insult in the LPS/Gln model. CTS-1027 significantly reduced ALT activity in the Fas and Con A models. Dosing was well below or equivalent to exposure levels previously tolerated in human clinical studies.
"CTS-1027 represents a potential new and exciting approach to treat patients infected with Hepatitis C Virus (HCV), and in the treatment of other liver diseases. Our initial goal for the development of CTS-1027 is to establish safety and efficacy in patients infected with HCV who have failed or can not tolerate standard of care," stated Alfred Spada, Ph.D., SVP Research and Development. "We plan to initiate a Phase 2 clinical trial within the next few months."
CTS-1027 is an oral, small molecule, matrix metalloproteinase (MMP) inhibitor under development for chronic use to protect the liver from damage due to a variety of insults including virus infection, obesity, alcohol use, and autoimmune diseases. Preclinical studies demonstrate strong efficacy in multiple models of liver disease. In previous clinical trials in other therapeutic areas, CTS-1027 was chronically administered to over 500 people, some for over 18 months.
Matrix metalloproteinases (MMPs) are a well studied family of proteolytic enzymes. In the liver, as in other solid organs, MMPs play a key role in maintaining the integrity of the extracellular matrix. Excessive MMP activity has been demonstrated to occur in the liver in response to a variety of acute and chronic insults. This results in the loss of scaffolding that maintains the normal architecture of the liver and the recruitment and activation of inflammatory cells that perpetuate liver damage. In addition, important cytokines in the progression of liver damage, such as TGF-beta, stimulate the expression of MMPs from hepatic stellate cells, the main cell type involved in the pathology of fibrosis. MMPs are also well recognized to play an important and direct role in regulating inflammation. These dual activities of tissue remodeling and modulating inflammatory networks make MMPs an attractive target in the setting of acute and chronic liver disease.
Conatus Pharmaceuticals Inc. is a privately-held specialty pharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease. Chronic liver disease affects millions of people worldwide and can be caused by many different conditions or "insults" to the liver including Hepatitis C and other viral infections, obesity, chronic alcohol abuse or autoimmune diseases. Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the successful sale of Idun to Pfizer.
http://www.conatuspharma.com/
Conatus Pharmaceuticals Inc.
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AASLD: Liver Transplant for HBV-Related End-stage Liver Disease Drops Dramatically
http://www.medpagetoday.com
By Nicholas Mulcahy,
Contributing Writer, MedPage Today
Reviewed by Robert Jasmer, MD;
Associate Clinical Professor of Medicine,
University of California, San Francisco
BOSTON, Nov. 4 -- The number of U.S. patients registered for liver transplantation for decompensated liver disease secondary to hepatitis B virus (HBV) has decreased by 37% since 2000, according to an epidemiological study presented here.
The decrease is likely the result of the widespread use of effective antivirals for HBV, W. Ray Kim, M.D., of the Mayo Clinic College of Medicine, reported at the American Association for the Study of Liver Diseases meeting.
"This is 'real-life' data that suggests antivirals can reduce the incidence of end-stage liver disease. Multiple [clinical] studies have shown that antivirals can reduce the incidence," said Dr. Kim.
Dr. Kim and colleagues analyzed data from the Organ Procurement and Transplantation Network waitlist from 1994 through 2006. The 125,800 patients included 6,087 with HBV, 41,021 with hepatitis C, and 79,937 with other conditions.
The number of registrants with HBV peaked in 2000 at 586 and dropped 30% to 409 in the ensuing 6 years. The decrease in HBV registrants since 2000 has not been mirrored among HCV registrants, which have stayed roughly the same, said Dr. Kim.
The HBV registrants included patients with end-stage liver disease (ESLD) and those with hepatocellular carcinoma (HCC). The decrease in the number of liver transplant registrants was pronounced among the ESLD patients.
From 2000 through 2006, the number of waitlist registrants with ESLD dropped 37% from 432 to 271. In contrast, the number of registrants with hepatocellular carcinoma increased 146% from 52 to 128 during this period.
The decrease in the number of liver transplant registrants with HBV was coincidental with the wide use of effective nucleoside and nucleotide analogues, Dr. Kim noted.
There are other possible explanations for the decrease in the number of ESLD liver transplant registrants, added Dr. Kim.
The implementation of the model for end-stage liver disease (MELD) scoring system in 2002 is one possible reason. "Patients who were previously categorized as ESLD may have been subsequently listed as HCC," he noted.
However, upon review, Dr. Kim and colleagues dismissed this cause and noted that during the study period the percentage of patients with either HBV or HCV and HCC in the waitlist grew but that the percentage with HBV grew less dramatically.
Another possible explanation might be that the total number of patients with HBV has decreased in the U.S. However, Dr. Kim noted that in the past 10 years there has been a 73% increase in Asian-Pacific Islanders in the U.S., with many being born in countries with high levels of HBV. "I don't think there is any dispute that hepatitis B is increasing in this country," he said.
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GlaxoSmithKline Initiates Trials of Promacta/revolade (eltrombopag) to Investigate the Potential to Aid Hepatitis C Patients in Achieving Sustained Virological Response
http://www.medadnews.com
LONDON, Nov. 5, 2007-GlaxoSmithKline (GSK) today announced the commencement of two parallel Phase III studies to assess the clinical benefits of its investigational compound PROMACTA
REVOLADE™ (eltrombopag) in hepatitis C-associated thrombocytopenia, a condition characterised by decreased platelet counts. The studies, ENABLE 1 and ENABLE 2 (Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE), will measure the ability of eltrombopag to raise platelet counts sufficiently enough to enable the initiation of antiviral therapy and to allow sustained antiviral therapy in thrombocytopenic hepatitis C patients. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve sustained virological response (SVR).
SVR is defined as an undetectable viral load of hepatitis C for a period of six months post-treatment and is the desired outcome of antiviral therapy. SVR is a determination that the hepatitis C virus is no longer replicating — a status that is viewed clinically to be an eradication of the virus and a decreased risk of disease progression.[1]
“The launch of both ENABLE trials is of great interest to many investigators in the field,” said John McHutchison, MD, Professor of Medicine and Associate Director, Duke Clinical Research Institute, Durham, North Carolina, US. “Thrombocytopenia is a complicating factor in hepatitis C treatment. Not only can it interfere with the administration of effective doses of antiviral therapy, but in some cases treatment may be terminated or not started at all. In a previous Phase II study, eltrombopag, compared to placebo, increased platelet counts and allowed more patients to complete the first 12 weeks of antiviral therapy, giving them an opportunity to achieve an SVR. ENABLE will investigate the effect of eltrombopag over a 12-month treatment period to determine how it may help patients to achieve SVR, which in clinical terms is considered a cure for hepatitis C, as well as better understand any related toxicities or tolerability issues.”
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) can occur as a result of damage to liver cells that produce thrombopoietin (the body’s natural platelet growth factor), or due to disease progression from cirrhosis. It may also occur as a consequence of antiviral (interferon) therapy used to treat HCV infection.[2],[3]
Combination antiviral treatment (peginterferon plus ribavirin) is the standard regimen used to control HCV infection.i This approach is critical for successful management of HCV and provides patients with the potential for a cure.
Eltrombopag is an investigational oral, non-peptide platelet growth factor. The ENABLE trials will investigate if eltrombopag will allow patients a greater opportunity to maximize the dose and duration of their antiviral therapy, thus improving the likelihood of achieving SVR. The ability to achieve and maintain SVR not only provides patients with clinical benefits, but is also shown to have a positive impact on quality of life with significant improvements in perceived wellness, vitality, social functioning and health distress.[4]
In addition, a Phase II subgroup analysis evaluating eltrombopag in hepatitis C patients will be presented at the forthcoming 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Massachusetts.[5]
Study Design
ENABLE 1 and ENABLE 2 are parallel, multi-center, two-part studies. Each consists of an open-label pre-antiviral treatment phase (Part 1) and a randomized, double-blind, placebo controlled, antiviral treatment phase (Part 2). Both studies will enroll approximately 750 patients with chronic hepatitis C infection (quantifiable HCV RNA) with baseline platelet counts of <75,000/?L. In Part 1 of the study all subjects will receive open-label eltrombopag in increasing doses for up to nine weeks before being randomized to double-blind eltrombopag or matched placebo in combination with antiviral therapy for up to 48 weeks (Part 2). ENABLE 1 will administer peginterferon alfa-2a plus ribavirin, while ENABLE 2 will investigate the use of peginterferon alfa-2b plus ribavirin. SVR rates will be assessed along with safety and quality of life outcomes.
Hepatitis C Prevalence
The World Health Organization (WHO) estimates that about 180 million people are infected with hepatitis C globally.[6] Three to four million new cases are diagnosed each year and 70% of these individuals go on to develop chronic hepatitis.[4] Hepatitis C is to blame for 50 — 76% of all liver cancers and two thirds of all liver transplants in the developed world.[6]
About Thrombocytopenia and Hepatitis C
A reduction in platelet count to a level <150,000/?L is the defining characteristic of any type of thrombocytopenia and diagnosis can be confirmed following a routine blood test. Thrombocytopenia occurs in 5% - 10% of all patients hospitalised for any cause.[7] The severity of thrombocytopenia varies. Mild to moderate cases may resolve spontaneously without treatment, however severe thrombocytopenia can be associated with significant morbidity and mortality.[2],[8] The cause of thrombocytopenia associated with hepatitis C is multi-factorial: inadequate thrombopoietin production by damaged liver, bone marrow suppression by interferon or viruses (HCV), sequestration of platelets in the spleen, and increased platelet destruction from an associated autoimmune process.
About Eltrombopag
Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown in pre-clinical research and clinical trials to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets, and thus can be considered a platelet growth factor. The safety profile will be further examined in ongoing clinical trials. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline.
Eltrombopag is an investigational compound that has not received regulatory approval in any market for any indication at this time.
About GlaxoSmithKline
GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit www.gsk.com.
Notes to Editors
REVOLADE™ and PROMACTA® are registered trade marks of the GlaxoSmithKline group of companies.
PROMACTA® is the proposed registered trademark to be used in the United States.
REVOLADE™ is the proposed trade mark for use in certain European countries.
To access the latest GSK Oncology media materials, visit www.gskcancermedia.com
REFERENCES
[1]Alberti A, Clumeck N, Collins S, et al. Short statement of the first European consensus conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. Journal of Hepatology 2005;42:615—624.
[2] Kaushansky K. The thrombocytopenia of cancer: prospects for effective cytokine therapy. Hematol Oncol Clin North Am. 1996;10:431-455.
[3]Ong JP, Younossi ZM. Managing the hematological side effects of antiviral therapy for chronic hepatitis C: Anemia, neutropenia, and thrombocytopenia. ClevelandClin Journal of Medicine. 2004;71(suppl 3):S17-S21.
[4]Bonkovsky HL, Woolley JM. The Consensus Interferon Study Group. Reduction of health-related quality of life in HCV and improvement with interferon therapy. Hepatology. 1999;29(1):277-279.
[5]Afdhal NH, McHutchison JG, Shiffman ML, et al. Eltrombopag raises platelet counts in two weeks in patients with HCV and significant thrombocytopenia. Abstract #42. Presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases. November 2-6, 2007. Boston, MA. Presented November 4, 2007.
[6]World Health Organisation. http://www.who.int/vaccine_research/diseases
/viral_cancers/en/index2.html. Accessed 18 July 2007.
[7]Mocharnuk R. Growth factors in granulocytopenia and thrombocytopenia. Presented at: 44th Annual Meeting of the American Society of Hematology; December 6—10, 2002; Philadelphia, Pa.
[8]Demetri GD. Targeted approaches for the treatment of thrombocytopenia. Oncologist. 2001;6 (suppl 5):15-23.
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November 6th, 2007
Ninety-one Percent of Baraclude (entecavir) Treated Patients in a Four-Year Cohort Demonstrated Virologic Suppression to Undetectable Levels
www.pharmalive.com
- In this Cohort of Nucleoside-Naive Chronic Hepatitis B e-Antigen (HBeAg) Positive Patients, Resistance Monitoring Identified One Patient with Genotypic Resistance to BARACLUDE -
BOSTON, November 02, 2007 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company today announced data from a four-year cohort (ETV-022/901, n=146), which showed that 91 percent (98/108) of patients treated with BARACLUDE(R) (entecavir) suppressed the amount of hepatitis B virus in the blood, or viral load, to undetectable levels(1) at week 192. Suppression of viral load to undetectable levels is a measure of antiviral treatment response; maintenance of viral load suppression is an important goal of chronic hepatitis B treatment. The results are being presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Patients in this cohort were nucleoside naive e-antigen (HBeAg)-positive patients with chronic hepatitis B infection. HBeAg is a viral protein identified as a marker of active replication of the hepatitis B virus. Patients in this cohort were initially treated with BARACLUDE 0.5 mg in study ETV-022 and continued treatment with BARACLUDE 1 mg by enrolling in study ETV- 901 with a less than or equal to 35 day treatment gap.
Resistance monitoring in this cohort identified one patient with genotypic resistance to BARACLUDE at week 139 who had a virologic breakthrough at week 148.
"The data indicate that BARACLUDE maintained viral suppression through four years of treatment in this patient population," said Hugo Cheinquer, M.D., Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil. "That a majority of BARACLUDE patients had undetectable viral load at four years with one patient developing resistance is very encouraging news for physicians who treat this chronic disease."
Safety events in this cohort were consistent with prior experience. Five deaths were reported in this cohort; no deaths were attributed to BARACLUDE(R) (entecavir). Twelve percent of patients experienced a serious adverse event. The most common adverse events occurring in greater than or equal to 10 percent of patients were: upper respiratory tract infection (31 percent), headache (21 percent), cough (17 percent), diarrhea (16 percent), influenza (17 percent), nasopharyngitis (16 percent), pyrexia (12 percent) and upper abdominal pain (10 percent).
About the Nucleoside-Naive HBeAg-Positive Four-Year BARACLUDE Cohort (n=146)
This four-year cohort evaluated long-term efficacy and safety of BARACLUDE in nucleoside-naive chronic HBeAg-positive patients who received four years of continued BARACLUDE treatment. The four-year cohort consisted of 146 patients who met the following criteria:
- Enrolled in study ETV-022, which compared the efficacy and safety of BARACLUDE 0.5 mg versus lamivudine 100 mg in nucleoside-naive chronic HBeAg-positive patients
- Enrolled in study ETV-901, which evaluated the efficacy and safety of BARACLUDE 1 mg, after a treatment gap of less than or equal to 35 days
- Some patients initially received combination of BARACLUDE 1 mg and lamivudine 100 mg for a mean of 26 weeks in study ETV-901. The mean duration of BARACLUDE 1 mg monotherapy was 194 weeks
The analysis cohort was defined regardless of treatment response at the end of dosing in study ETV-022 or viral load, HBV serology, or ALT measurements at the start of dosing in study ETV-901. Serologic testing was conducted by a central laboratory in study ETV-022 and by local laboratories in study ETV-901.
Resistance was comprehensively monitored in the BARACLUDE clinical program. Patients with HBV DNA levels of greater than or equal to 300 copies/mL at weeks 48, 96, 144, 192, or at the end of dosing were genotyped and a phenotype was determined for all novel emerging substitutions. All patients experiencing a virologic breakthrough (greater than or equal to 1 log(10) increase from nadir) were phenotyped even if they did not have emerging substitutions.
Study Results
- At week 192 of BARACLUDE(R) (entecavir) treatment, 91 percent (n=98/108) of nucleoside-naive chronic HBeAg-positive patients in this cohort achieved undetectable viral load (HBV DNA <300 copies/mL) and 86 percent (n=96/112) of patients achieved ALT normalization (ALT less than or equal to 1 times the upper limit of normal).
- During years three and four, an additional 41 percent (n=39/96) of patients lost HBeAg and 16 percent (n=15/96) of patients achieved HBeAg seroconversion.
- Resistance monitoring in this cohort identified one patient with genotypic resistance to BARACLUDE who later experienced virologic breakthrough.
- Safety events were consistent with previous experience. Additional cumulative safety results of patients reported in this four-year cohort:
- Ninety percent of patients had any adverse event.
- Grade 3-4 adverse events were reported in 13 percent of patients.
- There were no discontinuations due to adverse events in this cohort.
- Less than one percent of patients experienced on-treatment ALT flares during the fourth year.
About BARACLUDE(R) (entecavir)
Discovered at Bristol-Myers Squibb, BARACLUDE is a nucleoside analogue indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication with either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. In addition to the United States, BARACLUDE has been approved in more than 60 countries and regions around the world.
Indication and Important Safety Information About BARACLUDE(R) (entecavir) 0.5mg/1mg Tablets
BARACLUDE is a prescription medicine used for chronic infection with hepatitis B virus (HBV) in adults where the virus is multiplying and damaging the liver. BARACLUDE does not cure HBV or stop the spread of HBV to others. People should not take BARACLUDE if they are allergic to it or any of its ingredients. BARACLUDE has not been studied in children and is not recommended for anyone less than 16 years of age.
People taking BARACLUDE(R) (entecavir) should tell their healthcare provider right away if they feel very weak or tired, have unusual muscle pain, have trouble breathing, have stomach pain with nausea and vomiting, feel cold -- especially in their arms and legs, feel dizzy or lightheaded, or have a fast or irregular heartbeat, as they may be signs of a serious condition called lactic acidosis (buildup of an acid in the blood). Lactic acidosis is a medical emergency and must be treated in the hospital. Some people who have taken medicines like BARACLUDE have developed serious liver problems called hepatotoxicity. This may occur with liver enlargement (hepatomegaly) and fat in the liver (steatosis). People should call their healthcare provider right away if they get any of the following signs of liver problems: yellowing (jaundice) of the skin or the white part of the eyes, darkening of the urine, lightening in the color of bowel movements (stools), not feeling like eating food for several days or longer, feeling sick to the stomach (nausea), or having lower stomach pain. Lactic acidosis and hepatotoxicity have happened in some people taking medicines like BARACLUDE.
For people taking BARACLUDE who have or get HIV (the virus that can cause AIDS) and are not taking medicines for HIV at the same time, some HIV treatments that they may take in the future may be less likely to work. People are advised to get an HIV test before starting to take BARACLUDE and anytime that there is a chance they were exposed to HIV. BARACLUDE will not help HIV infection.
In some people, hepatitis B symptoms may get worse or become very serious when they stop taking BARACLUDE. People should not stop BARACLUDE without talking to their healthcare provider. Healthcare providers will need to follow their patients and do blood tests to check the liver when BARACLUDE is stopped. People should tell their healthcare provider if they have or develop kidney problems because their healthcare provider may want to do tests to see if a lower dose is needed.
Because BARACLUDE is removed from the body through the kidneys, a dose adjustment may be required. Healthcare providers may want to perform tests to determine whether a patient needs a lower dose or should take BARACLUDE less often than once a day.
It is not known if BARACLUDE is safe to use during pregnancy. It is not known if BARACLUDE helps to prevent a pregnant mother from passing HBV to her baby. A pregnant woman and her healthcare provider will need to decide if BARACLUDE is right for her. A woman should not breastfeed if she is taking BARACLUDE.
People should discuss with their healthcare provider all prescription and non-prescription medicines, vitamins, herbal supplements, and other health preparations they are taking or plan to take. BARACLUDE(R) (entecavir) may interact with medicines that leave the body through the kidneys. The safety and effectiveness of BARACLUDE in liver transplant recipients is unknown. The most common side effects of BARACLUDE in clinical studies were headache, tiredness, dizziness, and nausea.
This list of side effects is not complete at this time because BARACLUDE is still under study. People should report any new or continuing symptom to their healthcare provider. BARACLUDE should be taken once daily on an empty stomach (at least two hours after a meal and two hours before the next meal). To learn more about BARACLUDE and for Full Prescribing Information, including boxed WARNINGS, please visit http://www.bms.com/. Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
BARACLUDE(R) (entecavir) is a trademark of Bristol-Myers Squibb Company.
Full prescribing information for BARACLUDE, including boxed WARNINGS, is available at http://www.bms.com/.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life. Visit Bristol-Myers Squibb at www.bms.com.
(1) HBV DNA levels less than 300 copies/mL by polymerase chain reaction (PCR) assay.
CONTACT: Sonia Choi, +1-609-252-5132, , or Investors,John Elicker, +1-212-546-3775, , both of Bristol-MyersSquibb sonia.choi@bms.com john.elicker@bms.com
Web site: http://www.bms.com/
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Hepatitis C treatment reduces the virus but serious liver problems may progress
http://www.physorg.com
Patients with chronic hepatitis C and advanced liver disease who did not respond to previous standard therapy experienced significant decreases in their liver enzymes, viral levels, and liver inflammation following treatment with long-term pegylated interferon. However, the treatment did not slow or prevent the progression of serious liver disease.
These findings come from the clinical trial, Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) and were reported at the annual meeting of the American Association for the Study of Liver Disease in Boston on November 5, 2007. HALT-C is funded by the National Institutes of Health (NIH) with additional support from Hoffmann-La Roche Inc.
"The HALT-C trial unequivocally demonstrated that maintenance therapy with peginterferon does not prevent progression of liver disease among patients who have failed prior treatments," said James Everhart, M.D., project scientist for HALT-C and a program director for the Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the principal sponsor of HALT-C at NIH. "These results add to the incentive to develop more effective drugs that will benefit patients with severe liver disease due to hepatitis C."
HALT-C, a randomized multicenter trial of 1,050 patients with chronic hepatitis C who had failed prior treatment to eradicate the infection, assessed whether long-term treatment with peginterferon alfa-2a reduced the development of cirrhosis, liver failure, or liver cancer. The 517 patients randomized to the treatment arm received 90 micrograms of peginterferon in weekly injections for 3.5 years. The 533 patients in the control arm underwent the same follow-up and care as the treated patients including liver biopsies, quarterly clinic visits, and blood tests. All patients had advanced liver fibrosis, a gradual scarring of the liver that puts patients at risk for progressive liver disease.
The outcomes assessed in HALT-C were death, liver cancer, ascites (excess fluid in the abdomen), or encephalopathy (brain and nervous system damage), and for those who did not have cirrhosis initially, the development of cirrhosis. At the end of the study, 34.1 percent of the patients in the treated group and 33.8 percent of the patients in the control group had experienced at least one outcome. Patients in the treated group had significantly lower blood levels of the hepatitis C virus and less liver inflammation. However, there was no major difference in rates of any of the primary outcomes between groups.
Among treated patients, 17 percent stopped peginterferon by one year and six months and 30 percent stopped the drug two years later. Adverse events such as infections, musculoskeletal or digestive problems were the most common reasons patients stopped taking the drug.
Viral hepatitis C infects more than 100 million persons worldwide and as many as 4 million persons in the United States. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants in the United States each year. The best current antiviral therapy consists of pegylated interferon given by injection in combination with oral ribavirin prescribed for about 6 months to a year. This therapy eliminates the virus in about 50 percent of infected patients.
Source: NIH/National Institute of Diabetes and Digestive and Kidney Diseases
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November 7th, 2007
High court calls for hepatitis C settlement
http://www.asahi.com
THE ASAHI SHIMBUN
OSAKA--The high court here Wednesday urged drug makers and the state to accept a court-mediated settlement in a group action lawsuit filed by hepatitis C sufferers infected by tainted blood products.
Presiding Judge Katsutoshi Yokota's request came after the two parties last month expressed their intention to accept such an outcome.
"I judged that there is a possibility that a settlement can be reached (between the plaintiffs and the defendants)," Yokota said.
Details of the proposed deal were not available, but the judge said he would present his outline by around Dec. 7.
It is the first time that a judge has called for such a settlement in a group action suit filed by people infected with hepatitis C virus through tainted blood products.
In a previous hearing held Sept. 14, the high court proposed the idea in an effort to resolve the case quickly.
On Oct. 15, the plaintiffs proposed a settlement under which it wanted the state to acknowledge its legal responsibility and offer an apology.
The state also conveyed its intention to enter into talks on a court-mediated settlement.
Drug makers Mitsubishi Tanabe Pharma Corp. (formerly Mitsubishi Pharma Corp.) and its subsidiary Benesis Corp. also told the court they were prepared to enter into such talks.
The demands submitted by the plaintiffs in September have not been made public.
However, it is believed they are seeking an apology and compensation for all the plaintiffs of the several suits as well as permanent measures to treat all hepatitis C sufferers.
Rulings by five district courts were divided on the matter of state responsibility.
While districts courts of Osaka, Fukuoka, Tokyo and Nagoya ruled that the state was responsible for the use of tainted blood products, the Sendai District Court ruled otherwise.
But even among the four courts that recognized the state's responsibility, there was disagreement over which periods the state should be held responsible.
Lawyers for the government told the Osaka High Court that it would admit its legal responsibility only for a limited period, sources said.
Consequently, the state may show reluctance to paying compensation to all the plaintiffs from the different periods, according to analysts.
From October 2002, a series of group lawsuits were filed with the five district courts.
Currently, 171 patients are involved in trials in four district courts and five high courts.
In the Osaka High Court, 13 plaintiffs aged from their 20s to their 50s are seeking a total of 759 million yen in compensation from the state and the drug makers.
Late last month, Prime Minister Yasuo Fukuda said, "It cannot be said that the state is not responsible."
He then instructed Yoichi Masuzoe, minister of health, labor and welfare, to enter into talks for a court-mediated settlement.
Masuzoe said, "We will apologize for what we should apologize for and will pay compensation for what we should pay compensation for."(IHT/Asahi: November 8,2007)
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Consensus Interferon in Hepatitis C Is an Option for Those Non-Responsive to Peginterferon/Ribavrin: Presented at AASLD
http://www.docguide.com
By Maria Bishop
BOSTON, MA -- November 7, 2007 -- In a recent retrospective study of veterans, 12% of hepatitis C virus (HCV) subjects remained HCV ribonucleic acid (RNA) undetectable at least 3 months post-treatment with consensus interferon (Infergen) following prior treatment with peginterferon and ribavirin, researchers reported here at the 58th Annual Scientific Meeting of the American Association for the Study of Liver Disease (AASLD).
Treatment-naïve veterans fared better, with 24% remaining HCV RNA undetectable at least 3 months post-treatment with consensus interferon, noted lead author Helen S. Yee, PharmD, Ambulatory Care Clinical Pharmacist, Pharmacy Service, Department of Veterans Affairs (VA) Medical Center, San Francisco, California, United States.
These data offer an alternative for patients who are nonresponders/relapsers to peginterferon plus ribavirin. At least 50% of chronic HCV patients who receive standard therapy are nonresponders to treatment, added Dr. Yee.
Seven-hundred seventy-six of the hepatitis C patients who were reviewed for this study had been prescribed consensus interferon with ribavirin (99.7%) or without ribavirin in the VA health care system from October 2003 to October 2006. Treatment duration varied significantly between prescribers, and over 57% of the patients in this study discontinued consensus interferon within less than 3 months of starting treatment. The mean treatment duration averaged 3.1 months.
Data were reviewed for documentation of the following: HCV antiviral treatment history and response; time between HCV antiviral treatments; consensus interferon dose, frequency, and duration; and HCV RNA results. Demographic data were also included. The mean age of patients (95.4% of whom were male) was 55.4 ± 5.57 years. The average prior peginterferon treatment duration (n = 646) was 8.9 months.
"Factors associated with outcomes and consensus interferon [with or without ribavirin] -- such as dosing, length of treatment, and other practice variations -- need to be further assessed," concluded Dr. Yee.
This trial was funded in part by the VA National HIV/Hepatitis C Program and a grant from Valeant Pharmaceuticals, makers of Infergen.
[Presentation title: Hepatitis C Virus (HCV) Treatment Outcomes with Consensus Interferon with or without Ribavirin in Peginterferon/Ribavirin Non-responders/Relapsers: Results from National Clinical Practice Settings. Abstract 355]
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November 8th, 2007
Gilead Adds To Fibrotic Disease Pipeline In $202M Deal With LGLS
http://www.bioworld.com
By Jennifer Boggs
Staff Writer
Gilead Sciences Inc. is paying Korean firm LG Life Sciences Ltd. $20 million up front for rights to a caspase inhibitor program for fibrotic diseases, which includes a Phase II-stage compound being tested in patients with hepatitis C virus.
LGLS, based in Seoul, Korea, has been developing LB84451, an oral, once-daily, pan-caspase inhibitor, and other caspase inhibitors, which might have potential to stop the progression of fibrosis in the liver due to chronic hepatitis infections, as well as pulmonary fibrotic diseases.
Caspases, which are described as cellular proteases that are involved in processes such as apoptosis and inflammation "are a novel field of scientific research," said Nathan Kaiser, spokesman for Foster City, Calif.-based Gilead, which saw LGLS's caspase inhibitor program as a strategic fit.
"It aligns well with our interests in liver and our emerging focus on pulmonary diseases," he told BioWorld Today. On the liver side, Gilead markets Hepsera (adefovir dipivoxil) for hepatitis B virus (HBV) infection and, earlier this year, reported promising top-line Phase III data for Viread (tenofovir disoproxil fumarate) in HBV patients.
The company also is investigating non-nucleoside HCV polymerase inhibitors for hepatitis C virus. And last year, Gilead got a big boost to its pulmonary pipeline, with the acquisitions of Denver-based Myogen Inc. and Seattle-based Corus Pharma Inc.
Those deals brought late-stage drugs ambrisentan for peripheral arterial hypertension and aztreonam lysine for cystic fibrosis, respectively. (See BioWorld Today, July 21, 2006, and Oct. 3, 2006.)
Prior to its deal with Gilead, LGLS initiated Phase IIa testing of LB84451, looking for safety, tolerability, pharmacokinetic and efficacy data.
That study is expected "to be completed in the first half of 2008," Kaiser said, after which Gilead will determine the next steps. Besides HCV, the caspase inhibitor program could be explored in nonalcoholic steatohepatitis and idiopathic pulmonary fibrosis.
As development progresses, LGLS could receive up to $182 million in milestone payments, and would be entitled to an undisclosed royalty rate on product sales.
LGLS also retains rights to the caspase program in Korea, China and India, and holds worldwide rights to develop the program in ophthalmic and topical uses.
The Gilead deal is LGLS's second large collaboration this year. In March, the firm partnered with Osaka, Japan-based Takeda Pharmaceutical Co. Ltd. to develop obesity drugs based on LGLS' obesity program. In that deal, Takeda gained exclusive rights to compounds for worldwide commercialization, except Korea and Vietnam, with a semi-exclusive right in India, in exchange for up-front and research payments, as well as milestones, that potentially could exceed $100 million.
Gilead, which reported third-quarter earnings last month, posting a net income of $398.3 million, or 42 cents per share, revised its 2007 financial guidance to account for the $20 million payment to LGLS. It now expects R&D expenses for the year to fall between $510 million and $520 million, up from the previous guidance of $490 million to $500 million. The company ended the third quarter with about $2.2 billion in cash. (See BioWorld Today, Oct. 22, 2007.)
Gilead's shares (NASDAQ:GILD) closed at $44.62 Wednesday, down $2.49.
Published November 8, 2007
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Peregrine's bavituximab passes safety test
http://www.pharmaceutical-business-review.com
By Staff Writer
Peregrine Pharmaceuticals has reported positive results from its multiple dose, open label Phase lb study of bavituximab in chronic hepatitis C patients at the 58th Annual Meeting of the American Association for the Study of Liver Disease. Results indicate that bavituximab was generally safe and well tolerated, with no dose limiting toxicities or serious adverse events reported.
The study was designed to assess the safety and pharmacokinetic properties of ascending dose levels of bavituximab administered as monotherapy in patients with chronic HCV (hepatitis C virus) infection. Other study objectives included evaluation of anti-viral activity as measured by changes in serum HCV virus levels and an exploratory analysis of changes in serum cytokine levels as a measure of bavituximab's ability to stimulate certain components of the immune system.
Anti-viral activity (decline of greater than or equal to 0.5 log10 reduction in HCV RNA) was observed at all dose levels and was most consistent in patients receiving 3mg/kg of bavituximab. In this cohort, 83% of the patients demonstrated anti-viral activity. An assessment of the cytokine profile in this cohort also suggests bavituximab induces a pro-inflammatory cytokine profile, defined as an increase in the ratio of TNF alpha and TGF beta.
Steven King, president and CEO of Peregrine, said: "Meeting all of the objectives of this phase l trial was an important milestone for the bavituximab HCV program. We are particularly pleased with bavituximab's positive safety profile at all doses tested, its predictable and consistent pharmacokinetic characteristics, and the signs of anti-viral activity and immune system stimulation that were observed. Based on these results, we have been able to identify a target dose range of 3mg/kg for future clinical studies."
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Psychiatric Disorders Do Not Reduce Effectiveness of Hepatitis C Treatment: Presented at AASLD
http://www.docguide.com/
By Maria Bishop
BOSTON, MA -- November 8, 2007 -- Although comorbid psychiatric disorders at initiation of treatment for hepatitis C virus (HCV) are a risk factor for mental adverse events, they do not negatively affect the duration of pegylated interferon alfa-2b plus ribavirin treatment, adherence to treatment, or sustained viral response, researchers reported here at the 58th Annual Scientific Meeting of the American Association for the Study of Liver Disease (AASLD).
In clinical practice, patients infected with hepatitis C virus frequently have comorbid psychiatric disorders and are often drug users, noted Jean Philippe Lang, MD, Head of the Department of Psychiatry, Centre Hospitalier Erstein, Erstein, Cedex, France.
In a "real life" study called the CHEOBS study, factors related to compliance with the combination treatment of peginterferon alfa-2b (1.5 ug/kg/week) and ribavirin (800 to 1200 mg/day) were analysed in 1,972 HCV patients. The CHEOBS study is a prospective, observational study comprising 184 medical centres in France specialising in the management of hepatitis C.
Patient- and investigator-reported questionnaires were completed every 3 months; adherence was assessed every 3 months, as well.
Patients were divided into two groups: those not presenting with psychiatric disorders (NPPD) (n = 1,528) and those presenting with psychiatric disorders (PPD) (n = 444). A significantly greater proportion of patients in the PPD group had a history of injection or intranasal drug abuse, HCV genotype 3 infection, and chronic disease.
The rates of responders, nonresponders, and relapsers were similar between the PPD and NPPD groups, as was the proportion of adherent patients.
While the research team concluded the psychiatric disorders put HCV patients at risk for mental adverse events, they noted that psychiatric disorders did not reduce the effectiveness of hepatitis C Treatment.
Dr. Lang noted that the psychological effects of treatment with pegylated interferon alfa-2b plus ribavirin in fact negatively affected the quality of life of patients not presenting with psychiatric disorders (NPPD) more than it did those presenting with psychiatric disorders (PPD).
This trial was supported by funding from Schering-Plough.
[Presentation title: Assessment of the Impact of Psychiatric Disorders on Safety, Compliance, and Sustained Virological Response After Hepatitis C Treatment (CHEOBS). Abstract 906]
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Viral Vertigo
www.forbes.com
Robert Langreth
A drug for stealth killer hepatitis C has been years in the making. Hopes for a blockbuster are feverish.
If you want to know why drug research remains a slow and frustrating business even in this golden age of molecular biology, look at the troubles Vertex Pharmaceuticals (nasdaq: VRTX - news - people ) has gone through to devise a new drug to combat hepatitis C.
Hep C chronically infects 3.2 million Americans. The liver disease is spread through direct contact with | 
