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Week Ending: May 5th , 2007
Alan Franciscus
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This Issue:
April 28th, 2007
How Bad is Hepatitis C in Erie County?
http://www.wgrz.com
Mike Igoe, Reporter
The Town of Hamburg may not welcome this news.
The Erie County Health has started reviewing data on Hepatitis C and found the town of Hamburg has 19 reported cases since 2005. But Erie County Health Comissioner Dr. Anthony Bilittier says because the tracking of hepatitis C is new he's not sure if this is a high number.
Dr. Anthony Bilittier, Erie County Health Commissioner: "It's hard to say what's normal? What's the background? What do we normlly see in a community? If we have an outbreak then what's too much?"
Hepatitis C is virus that causes inflammation of the liver. Only certain people are at risk of contracting it.
Dr. Billittier: "Usually if they don't engage in risky behavior for example IV drug abuse or unprotected sex with multiple partners, they're not at risk for Hepatitis C."
Still the county's concerned for the people who are infected. The county health department says 80% of the people don't show any signs until they become chronically ill.
Dr. Billittier: "Some people with Hepatitis C will become yellow or jaundiced."
So the County will continue reviewing its data for all communities to try and get a handle on how bad the Hepatitis C situation really is.
Doctors who see patients with Hepatitis C are required by state law to notify their local health department.
But part of the challenge the county faces is that people who are at high risk may not even see a doctor.
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Needle exchange program
http://www.ketknbc.com
Jennifer Kielman
Some state lawmakers are trying to stop the spread of HIV and hepatitis C with a controversial new program.
The Senate recently passed a bill designed to help drug users, and although it hasn't hit the house floor just yet, it's causing quite a commotion for those KETK 56 News spoke with.
“I know there are cities in Europe, like Amsterdam that have started out with needle exchanges, and now it's the drug capitol of Europe.”
A new bill just passed by the state Senate would allow local health departments to start needle-exchange programs to help reduce the spread of disease by intravenous drug use.
The idea is to allow drug users to take their dirty needles to their local health department and switch them out for new ones.
The sponsor of the bill, state Senator Bob Deuell, says, "Needle-exchange programs were once thought to be a radical idea. But research shows that as many as 20 percent of addicts who participate in needle-sharing programs also seek drug-treatment programs."
The executive director of Tyler AIDS services, Reed Hunsdorfer, agrees.
Hunsdorfer said, “I don't think there's gonna be any more drug use. I think it'll be safer drug use, but people will find syringes and needles anywhere they can.”
On the other hand, those who oppose the bill say it'll promote drug use and doesn't send a very good message to East Texans.
“Anytime it has to do with introvene of injection of drugs, I just don't like it. I don't like the state getting into this business.”
In fact, Berman says he'll veto it once it hits the House floor.
“I don't want to attract drug users to Texas. I understand it could possibly save a life of some drug users and can get clean needles.”
He says the money that would be spent on the needle-exchange bill would be better spent on drug rehab programs.
To date Texas has more than 56,000 people living with the HIV virus. In Tyler there are about 300 people living with it.
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April 29th, 2007
Dose modification associated with poorer response to HCV therapy in HIV/HCV coinfected patients
www.aidsmap.com
Michael Carter
HIV-positive individuals coinfected with hepatitis C virus who modify their dose of anti-hepatitis C therapy reduce their chances of achieving a sustained response to hepatitis C therapy, according to the results of a US study published in the May 15th edition of Clinical Infectious Diseases.
Although the investigators did not find that modifying hepatitis C therapy due to haematological disorders was associated with a poorer treatment outcome, they believe that this could be because of the small number of individuals in the study, and, for this reason, the low number of treatment changes. They recommend that further, larger analyses are carried out to “more accurately assess the effect of haematologic toxicities”.
HIV, hepatitis C, and blood disorders
Significant numbers of HIV-positive individuals are coinfected with hepatitis C virus, and in the era of potent antiretroviral therapy, hepatitis C-related complications are becoming an increasingly important cause of illness and death in coinfected patients. It is well established that in coinfected patients, hepatitis C viral load is higher and progression to fibrosis, cirrhosis and liver cancer is faster, leading to increased mortality compared to patients who are only infected with hepatitis C.
Treatment for hepatitis C virus is available. The currently recommended standard of care consists of pegylated interferon plus ribavirin. The efficacy of this therapy is somewhat lower in coinfected patients than hepatitis C-monoinfected individuals.
Blood disorders, such as leukopenia (a reduced number of white blood cells), anaemia (reduced red blood cells), thrombocytopenia (reduced platelet count), and cytopenia (reduced cell count in the blood) can all be complications of HIV or hepatitis C virus infection. It is also known that anti-hepatitis C therapy can cause blood disorders, with ribavirin associated with anaemia, and interferon with thrombocytopenia and neutropenia (low neutrophil count – neutrophils are a type of white blood cell). Such blood disorders have been associated with the discontinuation of hepatitis C therapy, dose reduction, or the use of supporting therapies such as erythropoietin (EPO) and granulocyte-colony-stimulating factor (G-CSF).
The study
The ACTG A5071 study was designed as a prospective randomised trial to determine the safety and efficacy of two anti-hepatitis C treatment regimens in HIV-positive individuals. These regimens were interferon-alfa-2a plus ribavirin, or pegylated interferon-alfa-2a plus ribavirin.
Because of concerns about the overlapping haematologic toxicities of HIV and hepatitis C, and the side-effects associated with anti-hepatitis C therapy, the investigators conducted an analysis of their results to determine if the modification of anti-hepatitis C treatment, particularly for blood problems, influenced treatment outcome.
A total of 133 coinfected patients were randomised. All were aged 18 or over, had chronic HIV and hepatitis C infection, with a hepatitis C viral load above 600 IU/ml, and a CD4 cell count of 100 cells/mm3 if they were on antiretroviral therapy, or 300 cells/mm3 if they were not taking HIV therapy.
Screening for haematological disorders was undertaken prior to randomisation, and to enter the study patients were required to have a neutrophil count above 1000 cells/mm3, a haemoglobin concentration of 10g/dl or above, and a platelet count of 70,000 platelets/mm3 or greater.
The study lasted for 48 weeks and patients were monitored at regular intervals throughout.
Doses of the study medication were altered if a patient experienced side-effects, including blood disorders. At the discretion of an individual’s doctor, supportive therapy could be prescribed.
Results
Patients treated with pegylated interferon-alfa-2a were significantly more likely to reduce the dose of either pegylated interferon (p = 0.03), or ribavirin (p = 0.013), than individuals who were randomised to the interferon-alfa-2a arm. This difference was clear from week twelve of the study onwards.
However, the investigators found that reasons for treatment modifications did not differ significantly between patients in the two arms of the study. Neutropenia led to the majority of dose reductions (but no treatment discontinuations) in both the pegylated interferon and interferon arms. Anaemia was the cause of the majority of ribavirin dose reductions, and only one patient, stopped the drug because of this side-effect.
The risk of side-effects was not affected by an individual’s use of antiretroviral therapy, the particular HIV drugs taken, the use of AZT, CD4 cell count, hepatitis C genotype, or hepatic activity index.
No significant difference was observed between the two study arms in the number of patients who initiated supportive therapy with EPO. However, significantly more patients in the pegylated interferon arm commended treatment with G-CSF (p = 0.008).
Dose modification as a factor affecting the success of anti-hepatitis C therapy
Analysis showed that patients who modified their anti-hepatitis C therapy for any reason were significantly less likely to experience a successful response to hepatitis C therapy than patients who remained on unaltered therapy (p = 0.01).
Taking either EPO or G-CSF supportive therapy was significantly associated with a response to treatment (p = 0.04).
However, the investigators were unable to show if a treatment modification for blood disorders was significantly associated with a poorer treatment response. They observe that this finding was “limited by the fact that our clinical trial was not specifically designed to answer this question.”
They conclude “dose modification is associated with a lower response to therapy”, adding that it is important to study the outcome of individuals who modify doses for haematologic reasons “in larger clinical cohorts, to more accurately assess the effect of haematologic toxicities and the use of growth factors on the outcome of HCV therapy.”
Reference
Behler CM et al. Hematologic toxicity associated with interferon-based hepatitis C therapy in HIV type-1 coinfected subjects. Clin Infect Dis 44 (online edition), 2007.
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Living with a silent killer
http://www.newarkadvocate.com
By L.B. WHYDE
Advocate Reporter
Area residents battle deadly hepatitis C, urge others to be tested
NEWARK -- Kyle Morgan has been carrying around a silent killer for many years and didn't even know it.
Now, after a 48-week regimen of shots, she is hoping the hepatitis C virus will not return.
Hepatitis C is a virus that affects the liver. Only few indications of the virus exist, and often no symptoms are present until the liver begins to harden. The side effects of the treatment are similar to chemotherapy, including fatigue, flu-like symptoms, skin rashes, hair loss, anemia and irritability.
Morgan, 59, who is the director of academic advising at the Newark campus of Ohio State University, gave herself shots in the stomach once per week. Although she is not sure how she contracted the virus, the blood transfusion she received when she was 1 year old might have been the source of the contamination.
"I feel like I lost a year of my life," Morgan said. "It's been a nightmare (the treatments). I've been off the medicine a week, and I feel better already."
Hepatitis C is called the silent killer because of the lack of symptoms before the liver becomes hardened.
When it was discovered in a routine blood test in 2001, Morgan's hepatitis C was in stage 1. She was given the choice whether to treat the virus. After research and an online support group, Morgan decided against the treatment. Two years later, another biopsy was done; again, she denied treatment.
Then in 2006, after another biopsy, the doctors found the virus in stage 2 and told her she couldn't wait any longer to treat. After the seventh week of treatment, a test found the virus undetectable, but she still had to continue the 48-week regimen.
"The worst part of the treatment was during the last few months, I slept my weekends away, and I lost half my hair," Morgan said. "But I was able to work the whole time, and many cannot do that."
Morgan now will have to wait six months before she can find out if she is free of the virus.
John Eskins, 55, of Glenford, has been living with hepatitis C for many years but thinks he may have contracted it in 1969 when he served in the Army as a medic and came in contact with blood from a lot of people. In 1980, he felt run down and during a physical they found non A and non B chronic active hepatitis. This was before hepatitis C was named as a specifically different form of the virus. Now hepatitis is like "alphabet soup" said Eskins, because there even is a hepatitis G.
At one time several years ago, Eskins was on a liver transplant waiting list for four years. He was called in for a transplant twice, but both times the liver was not acceptable. He now has learned to live with the virus but still has his good days and his bad days. Now, his doctors don't even tell him his life expectancy, because he continues to outlive their projections.
"I improved," Eskins said. "I still have problems as I sleep a lot, get sick a lot and have trouble with my memory, but the liver is still there working, barely. Personally, I believe God helped me a lot on this."
While Eskins and Morgan and the millions of other people that carry the virus in their blood might not look sick, hepatitis C still is life-threatening.
"I just want to get the word out to people," Morgan said. "If they have the risk factors, they need to get their blood tested."
L.B. Whyde can be reached at (740) 328-8513 or lwhyde@newarkadvocate.com.
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Man died after kidney transplant from donor with hep. B
http://search.japantimes.co.jp
MATSUYAMA, Ehime Pref. (Kyodo) A man died of liver damage and severe pancreatitis after receiving a transplanted kidney from a hepatitis B patient and becoming infected with the virus, a hospital panel said Sunday.
The transplant was one of 25 transplants involving suspect kidneys conducted by urologist Makoto Mannami at the Uwajima Municipal Hospital in Uwajima, Ehime Prefecture, since the 1990s that recently came to light.
"It is reasonable to conclude that the transplant caused the virus infection, so we think there are substantial links between the death and the transplant," Katashi Fukao, head of the investigation panel, told a news conference, referring for the first time to causal links between the controversial transplants and the death of a patient.
"I don't think we can call this (proper) medical practice," Fukao added.
According to a report released by the panel, the man was one of two recipients of the kidneys taken in December 2000 by Mannami, 66, from a woman who tested positive for the hepatitis B virus.
The male recipient died about five months after the transplant, but the other person has not been infected with the virus so far and is still alive, the panel said.
The deceased man tested negative for the virus before the transplant but was found to be positive shortly before his death, it said.
Currently, a Health, Labor and Welfare Ministry directive bans transplants of kidneys harvested from dead donors who had cancer or hepatitis B, but there are no written rules concerning transplant of such organs from living donors.
Mannami, now a senior urologist at the Uwajima Tokushukai Hospital, said he thought infection would not occur at the time of the transplant. He also said the patient died of severe pancreatitis, insisting that the liver damage had no direct link to his death.
He is also known to have conducted 11 other transplants at the Tokushukai hospital using suspect kidneys after he moved from the Uwajima Municipal Hospital in March 2004.
The controversy has prompted the health ministry to review its guidelines on transplants of kidneys from sick patients. Members of a ministry panel working on the review are likely to conclude that the act of transplanting kidneys taken from patients due to the donors' medical needs should be banned in principle.
Proponents of this practice say it provides a solution to the chronic shortage of kidneys available for transplant.
In its report released Sunday, the Uwajima Municipal Hospital investigation panel said that all 25 transplants involving unhealthy kidneys conducted by Mannami at the institution were inappropriate.
The doctor failed to give sufficient explanations to the donors about the transplants, and there was no system in place to enable a third party to confirm whether the patients really consented to the operations, the report said.
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April 30th, 2007
Sebivo Approved in European Union as a New First-line Treatment for Chronic Hepatitis B
http://pharmalive.com
Sebivo provides more rapid and powerful viral suppression than lamivudine, the most widely prescribed treatment[1]
Rapid and powerful viral suppression has been shown to lead to better treatment outcomes[2]
Every year in Europe, 90,000 people will develop chronic hepatitis B and 24,000 will die from related complications such as cirrhosis or liver cancer[3]
BASEL, Switzerland, April 30, 2007 - The European Commission has approved Sebivo® (telbivudine) as a new first-line treatment for chronic hepatitis B that has been shown to provide rapid and powerful viral suppression within six months of starting therapy[1].
Approval was based on one-year data from the GLOBE study demonstrating the benefits of Sebivo over lamivudine, the most widely prescribed therapy worldwide, in achieving rapid and powerful suppression of the hepatitis B virus (HBV)[1].
"Chronic hepatitis B is a serious condition that can lead to liver cirrhosis, liver cancer, liver failure, and ultimately death," said Thierry Poynard, MD, PhD, Professor of Medicine and Head of the Department of Hepato-Gastroenterology, Hôpital Pitié-Salpêtrière, France. "There is no cure for chronic hepatitis B, but high viral load increases the risk of serious complications. To reduce this risk, the goal of therapy is therefore to suppress the hepatitis B virus as much as possible, and to maintain that decrease over time. The GLOBE study shows that telbivudine does this more effectively than lamivudine."
Every year in Europe an estimated one million people are infected with HBV and 90,000 will become chronic carriers[3]. The incidence of chronic hepatitis B (CHB) ranges from 29 cases for every 100,000 people in Western Europe to 523 per 100,000 people in Eastern Europe[4]. Approximately 24,000 people in Europe die each year from complications of CHB, including cirrhosis or liver cancer[3].
GLOBE is the largest worldwide registration trial ever conducted in patients with CHB and included 1,367 adult patients at 112 clinical centers in 20 countries. In the European Union, participating countries included the Czech Republic, France, Germany, Greece, Italy, Poland, Spain and the UK.
Data from the study also indicated that Sebivo works very quickly, suppressing HBV to undetectable levels (i.e. PCR negativity) in more than half of patients at six months of treatment, and that 95% of patients who achieved PCR negativity within this time retained their undetectable virus levels at one year1,2. Preliminary two-year results from the GLOBE trial, completed after the EU submission, demonstrated that these benefits were maintained through two years of treatment[5],[6].
"The results of the GLOBE trial showed that the rapid viral suppression achieved with Sebivo at six months can predict outcomes through two years of study," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "This is encouraging news for patients and physicians due to the fact that powerful viral suppression, early in the course of treatment, has been shown to be predictive of long-term viral suppression and minimal resistance. We are excited that Sebivo has now been approved in the European Union and can be made available to patients there."
Sebivo delivers this rapid, powerful and sustained viral suppression with an overall clinical safety profile similar to that of lamivudine. It is given once-daily with or without food, helping to ensure better compliance and patient convenience.
The European Committee decision applies to all 27 countries in the European Union as well as Iceland and Norway. Launches will start in the second quarter of 2007 beginning in the UK and Germany. In addition to the EU, Sebivo is currently approved in 16 major markets including the United States (where it is marketed as Tyzeka®), Canada, Switzerland and China.
About Idenix/Novartis collaboration
Novartis Pharma AG and Idenix are co-promoting Sebivo, for the treatment of hepatitis B, and co-developing valtorcitabine, a second hepatitis B compound, and valopicitabine, a hepatitis C compound, under a development and commercialization arrangement established in May 2003. Under this agreement, Novartis and Idenix will co-promote Sebivo, valtorcitabine and valopicitabine in the US, France, Germany, Italy, Spain and the UK. Novartis has the exclusive right to commercialize Sebivo, valtorcitabine and valopicitabine in the rest of the world.
Disclaimer
The foregoing release contains forward-looking statements which can be identified by the use of terminology such as "tentative approval," "pending expiration," "expected," "will," "could," "promises to be", or similar expressions, or by express or implied discussions regarding the potential final marketing approvals of Sebivo, or potential future revenue from Sebivo. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Sebivo will be approved for any other particular indications in the European Union or any other market, that Sebivo will be brought to market in the EU or in any other country, nor that Sebivo will reach any particular sales levels. In particular, management's expectations regarding the approval and commercialization of Sebivo could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; competition in general; increased government, industry, and general public pricing pressures; unexpected clinical trial results, including additional analysis of clinical data, or new clinical data; our ability to obtain or maintain patent or other proprietary intellectual property protection; and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.
References
[1] Lai, C. Hepatology. 2005 Oct (42.S1):78A.
[2] Zeuzem S, et al. Optimal virologic and clinical efficacy at one year is associated with maximal early HBV suppression in nucleoside-treated hepatitis B patients. J. Hepatol. 2006; 44 Suppl.2:S24.
[3] Van Damme P, et al. Hepatitis B prevention in Europe: a preliminary economic evaluation. Vaccine, Vol. 13, Supplement 1, pp. S54-S57, 1995 International Journal of Epidemiology; V.32; 2003; p118.
[4] Robert Koch Institute. Epidemiologisches Bulletin. 18. November 2005.
[5] Lai C-L, et al. Telbivudine vs lamivudine in HBeAg+ patients with CHB: two-year efficacy and predictors of response. Presented at APASL 2007.
[6] Liaw Y-F, et al. Telbivudine GLOBE Trial: 2 year efficacy and outcome predictors in HBeAg-negative patients with CHB. Presented at APASL 2007.
###
Media contacts
Corinne Hoff
Novartis Global Media Relations
+41 61 324 9577 (direct)
+41 79 248 5717 (mobile)
corinne.hoff@novartis.com
Birgit Gronkowski
Novartis Pharma Communications
+41 61 324 8790 (direct)
+41 79 820 1719 (mobile)
birgit.gronkowski@novartis.com
e-mail: media.relations@novartis.com
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Pro-Pharmaceuticals and Digna Biotech Sign Agreement to Apply DAVANAT® with Novel Drugs to treat Hepatitis C
http://home.businesswire.com
NEWTON, Mass.--(BUSINESS WIRE)--Pro-Pharmaceuticals, Inc. (Amex: PRW), a developer of first-in-class carbohydrate therapeutics, today announced it has signed an agreement with Digna Biotech SL of Pamplona, Spain to investigate the application of the Company’s carbohydrate technology platform in combination with Digna’s novel drugs to improve treatment of chronic Hepatitis C infections. The investigation will evaluate the ability of carbohydrate compounds to improve the delivery of Digna’s novel compounds to enhance activity against chronic Hepatitis C infections. Pro-Pharmaceuticals’ lead compound DAVANAT® will be the first carbohydrate compound to be evaluated as data from pre-clinical and clinical trials show that DAVANAT® increased the patient’s exposure to 5-FU ten-fold with no increase in toxicity.
"The collaboration with Digna is an important step in the development, commercialization and validation of our first-in-class carbohydrate technology," said David Platt, Ph.D, President & Chief Executive Officer, Pro-Pharmaceuticals, Inc. "Pharmaceutical companies continue to evaluate our technology for use with their compounds. The need to improve drug therapies, particularly anti-cancer agents, is significant and represents a large market opportunity. We believe our technology has the potential to play a major role in the worldwide treatment of patients with serious disease.”
Commercialization Strategy
The Company’s business objective is to develop DAVANAT® initially in combination with chemotherapeutics, and subsequently to rescue drugs that were shelved for toxicity or half-life issues; to use novel carbohydrate polymers to increase the solubility of known drugs, and to develop carbohydrate polymers as new chemical entities. Commercialization may be in the form of direct distribution, sales and marketing agreements, out licensing, or partnership with a biotechnology/pharmaceutical company. The Company plans to apply this approach in the U.S. as well as in other major international markets
The Company submitted data to the U.S. Food & Drug Administration (FDA) to allow DAVANAT® to be used as a functional excipient intravenously with 5-FU, for cancer applications for a filing under Section 505 (b)(2). The Company is using Section 505 (b)(2) to obtain more timely and efficient marketing approval of new formulations of previously approved therapeutics. The FDA requested additional chemistry, manufacturing and controls data. The Company plans to file a Master Drug File as soon as it completes the additional manufacturing information needed. 5-FU is one of the most widely used chemotherapy drugs in the world and is used to treat various types of cancers, including colorectal, breast and gastrointestinal.
The Company also plans to file a New Drug Application for DAVANAT® when it completes the two ongoing Phase II trials for first line treatment of colorectal and advanced biliary cancers and then conducts a pivotal Phase III trial.
In addition to DAVANAT®, the Company is developing a pipeline of carbohydrate-based therapeutic compounds that address other chronic diseases that are currently in the pre-clinical stage of development. The Company is testing a library of products—carbohydrate derivatives of marketed chemotherapeutics and biologics, including doxorubicin, irinotecan, oxaliplatin, cisplatin, paclitaxel, and bevacizumab (AVASTIN®). The Company is using its carbohydrate technology platform to develop novel anti-fibrosis (scarring of the liver) drugs through a research collaboration with Mount Sinai School of Medicine. The Company continues to develop and expand its pipeline of carbohydrates drug candidates in combination with other therapeutics and biologics for various indications.
About DAVANAT®
DAVANAT®, the Company’s lead drug candidate, is a polysaccharide (carbohydrate polymer) composed of mannose and galactose (galactomannan). The Company believes DAVANAT®’s mechanism of action is based upon binding to lectins on the surface of cells. It is theorized that DAVANAT® targets specific lectin receptors (Galectins) that are over-expressed on cells. Current research indicates that Galectins affect cell development and play important roles in cell survival. This form of targeted delivery may allow for higher doses of drug administration with no increase in toxicity.
About Digna Biotech SL
Digna Biotech SL is a privately held clinical stage biotechnology company located in Pamplona, Spain. Digna was founded in 2003 to license from and capitalize on all of the discoveries and innovation from the CIMA, the translational medicine center for the Universidad de Navarra with more than 300 scientists. Digna has partnered some of its projects with European bio-pharmaceutical companies including its lead project which is in Phase I testing for scleroderma. The Company has numerous other projects at various stages of pre-clinical testing. One of these is developing novel drugs for treatment of chronic Hepatitis C infections. The Company plans to file an IND in this indication in 2008.
Pro-Pharmaceuticals, Inc. – Advancing Drugs Through Glycoscience®
Pro-Pharmaceuticals is a development stage pharmaceutical company engaged in the discovery, development and commercialization of first-in-class carbohydrate-based therapeutic compounds for advanced treatment of cancer, liver, microbial, cardiovascular and inflammatory diseases. The Company’s initial focus is the development and commercialization of a new generation of anti-cancer treatments using carbohydrate polymers with the intent of enhancing the safety and efficacy of standard cancer agents. The Company’s technology capitalizes on the natural property of carbohydrates to increase the efficacy and reduce the toxicity of chemotherapeutics; “rescue” drugs that were shelved for toxicity or “half-life” issues; increase the solubility of existing drugs, and develop carbohydrate polymers as new chemical entities.
The Company has been conducting clinical and pre-clinical studies with its lead compound, DAVANAT®, in combination with 5-FU, leucovorin, irinotecan, doxorubicin, oxaliplatin, paclitaxel, cisplatin, and bevacizumab (Avastin®). Results show that DAVANAT® exhibits a broad spectrum of activity with tested drugs. The Company is developing additional carbohydrate-based therapeutic compounds that are currently in the pre-clinical stage of development. Founded in 2000, the Company is headquartered in Newton, Mass. Additional information is available at www.pro-pharmaceuticals.com .
FORWARD LOOKING STATEMENTS: Any statements in this news release about future expectations, plans and prospects for the Company, including without limitation statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements as defined in the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on management’s current expectations and are subject to a number of factors and uncertainties, which could cause actual results to differ materially from those described in such statements. We caution investors that actual results or business conditions may differ materially from those projected or suggested in forward-looking statements as a result of various factors including, but not limited to, the following: uncertainties as to the utility and market for our potential products; uncertainties associated with pre-clinical and clinical trials of our product candidates; our limited experience in product development and expected dependence on potential licensees and collaborators for commercial manufacturing, sales, distribution and marketing of our potential products; possible development by competitors of competing products and technologies; lack of assurance regarding patent and other protection of our proprietary technology; compliance with and change of government regulation of our activities, facilities and personnel; uncertainties as to the extent of reimbursement for our potential products by government and private health insurers; our dependence on key personnel; our history of operating losses and accumulated deficit; and economic conditions related to the biotechnology and bio-pharmaceutical industry. We cannot assure you that we have identified all the factors that create uncertainties. Readers should not place undue reliance on forward-looking statements.
More information about those risks and uncertainties is contained and discussed in the "Management Discussion and Analysis of Financial Condition and Results of Operations" and "Risk Factors" sections of the Company’s most recent quarterly or annual report and in the Company’s other reports filed with the Securities and Exchange Commission. The forward-looking statements represent the Company’s views as of the date of this news release and should not be relied upon to represent the Company’s views as of a subsequent date. While the Company anticipates that subsequent events may cause the Company’s views to change, the Company disclaims any obligation to update such forward-looking statements.
DAVANAT and Advancing Drugs Through Glycoscience are registered trademarks of Pro-Pharmaceuticals. AVASTIN is a registered trademark of Genentech, Inc.
Contacts
Pro-Pharmaceuticals, Inc.
Anthony D. Squeglia, 617-559-0033
squeglia@pro-pharmaceuticals.com
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European Union's CHMP Issues Positive Opinion on Pegintron and Rebetol Combination Therapy for Hepatitis C in Patients Coinfected With HIV
http://www.pharmalive.com/
KENILWORTH, N.J., April 30, 2007 /PRNewswire-FirstCall/ -- Schering-Plough Corporation today reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion recommending approval of combination therapy with PEGINTRON(TM) (peginterferon alfa-2b, 1.5 mcg/kg once weekly) and REBETOL(R) (ribavirin, 800 - 1,200 mg daily) for the treatment of previously untreated adult patients with chronic hepatitis C who are coinfected with clinically stable HIV. Approximately 40 percent of the estimated 2.5 million people living with HIV in Europe are coinfected with the hepatitis C virus (HCV), according to the World Health Organization (WHO).
The CHMP recommendation serves as the basis for a European Commission approval of this expanded indication for PEGINTRON and REBETOL combination therapy, which is currently approved in the European Union (EU) for treating chronic hepatitis C in previously untreated adult patients. Upon approval, this new coinfection indication will result in Marketing Authorization with unified labeling that will be valid in the current EU 27 member states as well as in Iceland and Norway.
In two clinical studies, HCV/HIV coinfected patients treated with PEGINTRON combination therapy achieved higher statistically significant sustained virological response (SVR) rates overall compared to conventional interferon alfa-2b and ribavirin.(1,2) SVR is defined as undetectable HCV-RNA six months following the end of treatment and is the standard measure of treatment success for hepatitis C.
Importantly, PEGINTRON combination therapy demonstrated a predictable response in HCV/HIV coinfected patients. Early virological response by treatment week 12, defined as a 2 log viral load decrease or undetectable levels of HCV-RNA, has been shown to be predictive for SVR. The negative predictive value for SVR in HCV/HIV coinfected patients treated with PEGINTRON combination therapy was 99 percent.(1) This means patients with hepatitis C who fail to achieve an early virological response are highly unlikely to become sustained virological responders and can stop therapy with confidence. This can be critical to the effective management of coinfected patients, who are at greater risk for treatment-related adverse events.
Liver disease caused by chronic hepatitis C virus is now a leading cause of morbidity and mortality among HIV patients in the developed world, where deaths due to AIDS-related diseases have declined dramatically as a result of the widespread use of highly active antiretroviral therapy (HAART) for HIV.
"HCV/HIV coinfection represents a complex treatment challenge and a major concern for patients, as hepatitis C in coinfected individuals appears to have a more aggressive course," said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute. "As a result, effective treatment of HCV is critically important for people living with HIV. The CHMP recommendation for approval of weight-based PEGINTRON combination therapy further underscores the benefits of PEGINTRON HCV treatment."
Clinical Studies
The CHMP recommendation for approval of PEGINTRON and REBETOL combination therapy for HCV/HIV coinfection is based on the results of two published clinical studies in previously untreated adult patients with chronic hepatitis C who were coinfected with HIV. RIBAVIC(1) was a multicenter study that randomized 412 patients to receive either PEGINTRON or conventional interferon alfa-2b (3 MIU three times weekly) in combination with flat-dosed ribavirin (800 mg daily) for 48 weeks. The second study(2) was a randomized, single- centre study in which 95 patients were randomized to receive either PEGINTRON or conventional interferon alfa-2b in combination with weight-based REBETOL (800-1,200 mg daily) for 48 weeks, except for patients infected with HCV genotypes 2 or 3 and HCV viral load less than 800,000 IU/ml (Amplicor) who were treated for 24 weeks.
Based on the results of these studies, the CHMP recommended duration of dosing with PEGINTRON and REBETOL combination therapy for HCV/HIV coinfected patients is 48 weeks, regardless of HCV genotype.
PEGINTRON in the European Union
PEGINTRON and REBETOL combination therapy for chronic hepatitis C was approved in the EU in March 2001. The recommended dose in the EU for combination therapy is PEGINTRON 1.5 mcg/kg once weekly plus REBETOL 800-1,200 mg daily, adjusted to body weight. The recommended duration of treatment is 24 weeks for patients with HCV genotype 1 and low viral load, or HCV genotype 2 or 3. For patients with HCV genotype 1 and high viral load or HCV genotype 4, the recommended duration of treatment is 48 weeks. PEGINTRON had previously received centralized marketing authorization in the EU and is marketed as a monotherapy in cases of intolerance or contraindication to ribavirin for the treatment of adult patients with chronic hepatitis C.
Chronic hepatitis C is estimated to affect more than 10 million people in major world markets, including 5 million in Europe. It is a leading cause of chronic liver disease and one of the most common reasons for liver transplant in Europe.
PEGINTRON in the United States
PEGINTRON is not approved in the United States for treatment of HCV/HIV coinfected patients. In the United States, PEGINTRON is indicated for use alone or with ribavirin for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age.
Important Safety Information Regarding U.S. Labeling for PEGINTRON and REBETOL
WARNING
Alpha interferons, including PEGINTRON, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping PEGINTRON therapy.
Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.
REBETOL and combination REBETOL/PEGINTRON therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. REBETOL and combination REBETOL/PEGINTRON therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (at least two reliable forms) during treatment and during the 6- month post-treatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling (800) 727-7064.
PEGINTRON
There are no new adverse events specific to PEGINTRON as compared to INTRON(R) A (Interferon alfa-2b, recombinant) for Injection; however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with PEGINTRON were "flu- like" symptoms, occurring in approximately 50 percent of patients, which may decrease in severity as treatment continues. Application site disorders were common (47 percent), but all were mild (44 percent) or
moderate (4 percent) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2 percent of patients receiving PEGINTRON. Alopecia (thinning of the hair) is also often associated with alpha interferons including PEGINTRON.
Psychiatric adverse events, which include insomnia, were common (57 percent) with PEGINTRON but similar to INTRON A (58 percent). Depression was most common at 29 percent. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1 percent of patients during or shortly after completing treatment with PEGINTRON.
PEGINTRON/REBETOL is contraindicated in patients with autoimmune hepatitis, decompensated liver disease, and in patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia). The following serious or clinically significant adverse events have been reported at a frequency less than 1 percent with PEGINTRON or interferon alpha: severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton wool spots.
In the PEGINTRON/REBETOL combination trial the incidence of serious adverse events was 17 percent in the PEGINTRON/REBETOL groups compared to 14 percent in the INTRON A/REBETOL group. The incidence of severe adverse events in the PEGINTRON/REBETOL combination therapy trial was 23 percent in the INTRON A/REBETOL group and 31-34 percent in the PEGINTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42 percent of patients receiving PEGINTRON (1.5 mcg/kg)/REBETOL and in 34 percent of those receiving INTRON A/REBETOL.
REBETOL should not be used in patients with creatinine clearance less than 50 mL/min. Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its approximately 33,500 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the potential of PEGINTRON and REBETOL. Forward-looking statements relate to expectations or forecasts of future events. Schering- Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering- Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details of these and other risks and uncertainties that may impact forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 1A, "Risk Factors" in the company's first quarter 2007 10-Q.
References:
1. Carrato F, Bani-Sadir F, Pol S et al. JAMA 2004; 292(23): 2839-2848.
2. Laguno M, Murillas J, Blanco J et al. AIDS 2004; 18(13): F27-F36.
CONTACT: Media: Robert J. Consalvo, +1-908-298-7409; Investors: AlexKelly, +1-908-298-7436, or Robyn Brown, +1-908-298-7436
Web site: http://www.schering-plough.com/
Company News On-Call: http://www.prnewswire.com/comp/777050.html/
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Governors Kulongoski and Gregoire Proclaim May 2007 Hepatitis Awareness Month :"The Silent Epidemic" Gains Voices
http://www.sys-con.com
By: Marketwire
OREGON CITY, OR -- (MARKET WIRE) -- 04/30/07 -- The Hepatitis C Caring Ambassadors Program (HCCAP) applauds Governors Kulongoski and Gregoire for recognizing viral hepatitis as a serious threat to public health by issuing proclamations recognizing Hepatitis Awareness month in their respective states. Hepatitis C is the most common chronic, blood-borne viral infection in the United States, and is the leading cause of chronic liver disease. An estimated 5 million Americans have been infected with the hepatitis C virus (HCV) including at least 171,000 citizens in Oregon and Washington.
HCCAP Program Director, Lorren Sandt, said of the proclamations, "Raising awareness among the general public about hepatitis C is especially important since the majority of people living with hepatitis C remain undiagnosed. People cannot change the course of their disease or protect their loved ones if they are unaware of their own health status."
HCCAP's efforts during Hepatitis Awareness Month are focused on educating the general public and policy-makers about both the health threat posed by hepatitis C and the opportunity to turn the tide on this public health crisis. The death rate from hepatitis C is expected to triple from 2010 to 2019. Increased testing and treatment can help curb this dire prediction. "Hepatitis C is a rarity among viral illnesses in that we have medications that cure the disease in approximately half of those who undergo treatment," said Dr. Tina St. John, Medical Director of HCCAP. She added, "In the near future, we hope to improve therapies so that cure is possible in nearly all people treated. There are several products currently in clinical trials showing very promising preliminary results."
Lorren Sandt noted, "The number of people in Oregon and Washington living with hepatitis C would fill the Rose Garden more than 8 times. We have an opportunity to help every one of those individuals, but we must act now. Thank you, Governors Kulongoski and Gregoire, for taking action!"
About Hepatitis C Caring Ambassadors Program
The Hepatitis C Caring Ambassadors Program (HCCAP) is a division of the national nonprofit public charity, the Caring Ambassadors Program, Inc. Headquartered in Oregon City, Oregon, HCCAP is committed to improving the health and longevity of those living with chronic hepatitis C through information, awareness, and public advocacy.
Contact:
Lorren Sandt
503-632-9032
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Tackling high rates of HIV and Hepatitis C in UK prisons
http://www.careandhealth.com
Prisons are facing a health crisis in the UK, due to the failure of prison health services to adequately deal with the extremely high rates of HIV and Hepatitis C among prisoners
In an attempt to reduce high rates of infection and prevent sub-standard health care for prisoners, the National AIDS Trust today launches guidance on responding to HIV, Hepatitis C and other blood-borne viruses in prisons.
Prisoners in the UK are disproportionately affected by blood-borne viruses.
The most recent figures available, from 1997, showed that prisoners were fifteen times more likely to be infected with HIV and over twenty times more likely to be infected with Hepatitis C than the general population in the UK.
Ten years on, experts predict that prisoners are now even more likely to be infected with one or more blood-borne virus.
Prisoners are particularly vulnerable to becoming infected with HIV or Hepatitis C as many have engaged in high-risk activity such as injecting drugs or sex work. The current prison environment also exacerbates the spread of blood-borne viruses.
Although it is illegal, injecting drug use regularly takes place in prisons and often involves the sharing of needles. A large number of prisoners will also have unprotected sex during their time in prison.
The National AIDS Trust has produced Tackling Blood Borne Viruses in Prison- A framework for best practice in the UK, in consultation with an expert working group, which includes experts in prison health, communicable diseases and genito-urinary medicine, as well as prison governors and representatives from key prisons associations.
The guidelines were developed in response to the findings of a survey of UK prisons conducted by the Prison Reform Trust and the National AIDS Trust in 2005, which identified serious failings in the current system, both in terms of prevention and treatment.
The survey revealed that, despite some examples of good practice, many prisons could do more to protect prisoners from blood borne viruses and ensure prisoners were receiving inadequate healthcare in relation to both HIV and Hepatitis C.
This has grave consequences both for the health of individual prisoners and, more generally, for public health through an increased risk of onward transmission.
Deborah Jack, Chief Executive of the National AIDS Trust, comments:
“This evidence-based framework gives clear guidance on how to tackle some of the key problems currently preventing an effective response to HIV and Hepatitis C in UK prisons, including inadequate education and access to prevention methods, lack of medical expertise, and the frequent moving of prisoners.
The implementation of these guidelines will have a significant impact, by reducing onward transmission, encouraging early diagnosis through voluntary and confidential testing and ensuring access to high quality treatment and care for those infected with HIV and Hepatitis C”.
This unique resource will be a useful tool for those who have responsibilities for the health and well being of prisoners and prison staff in the UK; Prison Governors, heads of healthcare and those responsible for commissioning and delivering services in prisons.
The guidelines have been launched at a pivotal time for prison health, as since April 2006, NHS Primary Care Trusts have been responsible for health services in every publicly run prison in England and Wales, and the Department of Health have pledged to provide an equivalent standard of healthcare in prisons as that in the community.
Dame Ruth Runciman, Deputy Chair of the Prison Reform Trust and former Chair of the National AIDS Trust, comments:
“The response to HIV and Hepatitis C in prisons in the last two decades, both in terms of policy and practice, has been entirely inadequate, and these failings need to be addressed as a matter of urgency.
At a crucial time for prison health, this pioneering initiative has the potential to significantly improve the response of prisons to blood-borne viruses, which will have enormous benefits for both individual and public health.”
This practical guide offers gives clear direction and examples of what needs to be done to improve the UK’s response to blood-borne viruses in prisons, setting out best practice from the moment a prisoner enters the system until after their release. Topics covered include:
- Developing a strategic policy on HIV and Hepatitis C
- Identifying opportunities for prevention and testing during the prisoner pathway
- Meeting needs of staff in terms of occupational health, risk assessment and training
- Promoting health and inequality and tackling stigma and discrimination
The framework is available to order or download from www.nat.org.uk
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ICMR, HANRC of Germany join hands to develop Hepatitis C vaccine
http://www.pharmabiz.com
Nandita Vijay, Bangalore
In a major effort towards developing the Hepatitis C vaccine in India, Indian Council of Medical Research (ICMR) and Helmoholtz Association of National Research Centre (HANRC) of Germany have reached an agreement to form the Indo German Science Centre for Infectious Diseases (IGCID).
The pact will allow the scientists from both India and Germany to undertake research on the vaccine development for the deadly disease. The experiments on mice will begin in July this year in association with the National Institute of Virology (NIV), Pune.
To pursue the research programme, experts from HANRC would visit India with their specially designed mice, which will be used to test the virus for the deadly disease. The Hepatitis C affects an estimated 1.5 million people in the country.
A high level delegation from Germany led by Prof. JM Lynek, president, HANRC along with a team of 11 scientists are currently on a visit to India.
NIV, which will be the centre for research, has upgraded its facility and has the capability to test the virus. The German experts have designed the mice to test the strains of the virus. The NIV has different strains of the virus besides the molecular information. Both of these form the starting point of the experiment. All the logistics for the research have been worked out and if all goes well, the country could be on its way to be able to produce a vaccine for the virus, informed Prof NK Ganguly, director general, ICMR.
The research for Hepatitis C comes as a result of a scientific cooperation pact inked between both India and Germany. The two countries also went on to sign a memorandum of understanding between the Indian Prime Minister Dr Manmohan Singh and Chancellor of Germany Angela Merkel, stated Prof Ganguly who was in Bangalore.
The ICMR DG also informed that the Central government would provide adequate fund to the project apart from administering collaborative budgetary efforts and promoting exchange of scientists and hold joint workshops.
A unique feature of the special mice models is that its immune system developed by Germany is akin to the humans and has the ability to replicate the disease. The NIV centre has recently set up a new research centre which is geared up not only to work in areas of virology, development of vaccines but also other anti-infectious diseases.
Presently, there are no animal models that can be used for Hepatitis C experiments in vaccine development. This is one of the reasons why the vaccine for the virus could not be developed anywhere in the world. These mice have been designed by experts and can replicate the disease as in the case of humans.
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May 1st, 2007
Racial Disparities in Treatment of Patients With Cirrhosis and Complications of Portal Hypertension
http://www3.interscience.wiley.com
African-American and Hispanic Patients Receive Less Palliative and Lifesaving Treatment
African-American and Hispanic patients hospitalized for complications of portal hypertension were less likely to undergo a palliative shunt, prompt endoscopy, or liver transplantation compared to white patients, according to a new study in the May issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online via Wiley Interscience (http://www.interscience.wiley.com/journal
/hepatology).
Liver disease is very common in the United States and as it progresses, patients develop portal hypertension-related complications, such as variceal bleeding, ascites or hepatic encephalopathy. These patients should be considered for liver transplantation, without which they face a 2-year survival prognosis of less than 50 percent. While awaiting transplants, they may be candidates for palliative procedures including endoscopic band ligation or portosystemic shunts.
Previous studies have revealed widespread racial disparities in disease treatments and outcomes. To determine the influence of race and health insurance for patients with serious liver disease, including their likelihood of receiving palliative procedures or transplants, researchers, led by Paul J. Thuluvath. MD (and Geoffrey Nguyen, Fellow in Gastroenterology & Hepatology) of Johns Hopkins University School of Medicine examined a nationally representative, population-based sample of hospitalized patients with cirrhosis and complications of portal hypertension.
Using the Nationwide Inpatient Sample, the researchers included 63,696 patients with cirrhosis who were admitted to a hospital between 1998 and 2003 for a complication of portal hypertension. The researchers gathered demographic data, information on health insurance and treatment efforts, and then performed statistical analyses, adjusting for potential confounding factors. They found that during hospital stays, African-American and Hispanic patients were significantly less likely than white patients to receive a portosystemic shunt, a prompt endoscopic variceal hemostasis, or a liver transplant.
Compared to white patients, the odds ratio of undergoing portosystemic shunt for was .37 for African-Americans, and .69 for Hispanics. Similarly, the odds ratio of undergoing liver transplantation was .32 for African-Americans and .46 for Hispanics. For patients with variceal bleeding, rates of upper endoscopy and variceal treatment were similar, however, the odds ratio of delayed endoscopy (more than 24 hours after admission) was 1.6 for African-American patients, compared to white patients. African-American patients were more likely to die in the hospital compared to white patients, while Hispanic patients were less likely than white patients to die in the hospital.
Relative to those who had private insurance, patients receiving Medicare, Medicaid or who were uninsured were less likely to undergo a shunt procedure, more likely to have a delayed endoscopy, and much less likely to receive a liver transplant.
“We have shown that there are striking racial variations in surgical and endoscopic procedures used in the inpatient management of complications of portal hypertension in the USA,” the authors report. “The reasons for these racial differences are unclear from this study.”
While non-medical factors such as health care access may play a contributing role, the authors also found that racial differences were independent of type of health insurance. They suggest that disease severity, for which they were unable to control, might also play a role.
“Further primary studies are warranted to confirm and elucidate the mechanisms of racial disparities in order to enact interventions to rectify them,” the authors conclude. “Concurrently, it is a measure of good practice and quality of care to develop more standardized protocols in the management of portal hypertension to ensure equitable care regardless of race, health insurance coverage, or socioeconomic status.”
"Racial Disparities in the Management of Hospitalized Patients with Cirrhosis and Complications of Portal Hypertension: A National Studym," Nguyen, Geoffrey; Segev, Dorry; Thuluvath, Paul, Hepatology; May 2007; (DOI: 10.1002/hep.21580)
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Liver Stiffness Indicates Portal Hypertension
http://www3.interscience.wiley.com
Measurement is less invasive than alternatives
Measuring liver stiffness using transient elastography can predict severe portal hypertension in patients with hepatitis C-related cirrhosis, according to a new study in the May issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at http://www.interscience.wiley.com
/journal/hepatology.
As liver disease progresses, fibrosis leads to portal hypertension which causes potentially lethal complications such as variceal hemorrhage, ascites and portosystemic encephalopathy. Measuring the hepatic venous pressure gradient (HVPG) is the standard method used to assess portal pressure and predict its complications; however, the procedure is invasive, expensive, and requires technical expertise.
In search of another way to assess liver fibrosis and portal hypertension, researchers, led by Massimo Pinzani, MD, PhD, of the University of Florence, sought to evaluate transient elastography, a rapid, non-invasive technique to measure liver stiffness. They compared its accuracy in detecting portal hypertension and its complications with that of HVPG measurement.
Between March 1, 2005 and July 1, 2006, the researchers studied 61 consecutive patients with diagnosed or suspected cirrhosis from chronic HCV infection. Each patient underwent transient elastography to measure liver stiffness. Immediately afterward, they underwent HVPG measurement and liver biopsy. The researchers then analyzed the data and compared the diagnostic tools.
“Considering the whole patient population, a statistically significant, positive correlation between HVPG and liver stiffness measurement was found,” they report. The correlation was excellent for HVPG values less than 10 or 12 mmHg, but not as good for greater HVPG values. They also noted a correlation between liver stiffness measurement and the presence of esophageal varices, however, the negative and positive predictive values for the detection of varices were unsatisfactory, at 66 percent and 77 percent respectively.
“We suggest that measurement of liver stiffness by transient elastography may represent a reliable non-invasive methodology for the prediction of clinically significant and severe portal hypertension, although not good enough to replace endoscopy for the detection of varices,” the authors conclude.
An accompanying editorial by Joseph Lim of Yale University School of Medicine and Roberto Groszmann of VA Connecticut Healthcare System and Yale University applauds the study as the first to evaluate the correlation between liver stiffness measurement and clinically significant portal hypertension as reflected by both direct HVPG measurement and the identification of esophageal varices on upper GI endoscopy.
“Additional validation studies evaluating its diagnostic accuracy in a representative American population are needed prior to regulatory approval and wide application to clinical practice,” the editorial authors note, particularly because the average BMI of the study population was 23, which contrasts to higher mean BMIs in the U.S. population. To date HVPG still is the gold standard.. for predicting clinical decompensation and the response of portal pressure to pharmacological therapy.
"Liver Stiffness Measurement Predicts Severe Portal Hypertension in Patients with HCV-Related Cirrhosis"
Vizzutti, Francesco; Arena, Umberto; Romanelli, Roberto; Rega, Luigi; Foschi, Marco; Colagrande, Stefano; Petrarca, Antonio; Moscarella, Stefania; Belli, Giacomo; Zignego, Anna Linda; Marra, Fabio; Laffi, Giacomo; Pinzani, Massimo
Hepatology; May 2007; (DOI: 10.1002/hep.21665)
"Transient Elastography for Diagnosis of Portal Hypertension in Liver Cirrhosis: Is There Still a Role for Hepatic Venous Pressure Gradient Measurement?" Lim, Joseph; Groszmann, Roberto, Hepatology; May 2007; (DOI: 10.1002/hep.21731)
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Some 35,000 people in Ontario have hepatitis C and don't know it: gov't ads
http://ca.news.yahoo.com
TORONTO (CP) - Some 35,000 people across Ontario are infected with hepatitis C and don't know it, provincial health officials said Tuesday.
The statistic is part of an advertising campaign that will include TV commercials in eight different languages, ads in almost 300 newspapers, and an online campaign to raise awareness in Ontario. The ads will point people to a new website, www.hepContario.ca, which includes an anonymous quiz to determine whether you're at risk for contracting the disease.
Hepatitis C, commonly spread through intravenous drug use, can cause cirrhosis and liver cancer.
It's possible to live with the disease for several years without experiencing symptoms, said Dr. David Wong, a hepatologist at Toronto Western Hospital.
"In the '60s, if you used that one or two needles, you may have hepatitis C," said Wong.
"If you lived in a country at a time where they were not throwing away their syringes, but were actually vaccinating everybody with the same needle, you may have hepatitis C from 40 years ago and not know it."
Keith Barry, a member of Ontario's hepatitis C task force, was infected during a blood transfusion in 1979 but wasn't diagnosed until 1989. He called the awareness campaign invaluable.
"When I was diagnosed in 1989, these tools didn't exist," said Barry. "I staggered around in the dark for a long time, not knowing where I was or what I was going to do, in a mass confusion. Today, people don't have to do that."
Such campaigns have an important role to play in dispelling myths about hepatitis C, he added.
"There are still people that come and speak to me and say, 'You know, I'm being stigmatized at work. I'm being stigmatized by my friends and my family,' " said Barry.
"If I can help that, then I've done my job."
Overall, officials say about 110,000 Ontarians have the viral infection.
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DiaSorin Provides Hepatitis Training to Laboratory and Healthcare Workers
http://www.redorbit.com/
DiaSorin Inc. and the National Laboratory Training Network (NLTN) will present the second in a series of three hepatitis web conferences on hepatitis A, B and C, "Understanding Hepatitis B" by Wendi Kuhnert, PhD, Centers for Disease Control and Prevention (CDC) on May 16, 2007. This training is offered via audio or web conference to healthcare workers performing public health, clinical, and environmental laboratory testing. 500 laboratory professionals attended the first web conference "Understanding Hepatitis A" on January 17, 2007. The National Laboratory Training Network is a training system sponsored by the Association of Public Health Laboratories (APHL) and the Centers for Disease Control and Prevention (CDC).
Infection with hepatitis viruses continues to be a health threat in the United States and many parts of the world. Any person with a hepatitis virus infection is a potential source of infection to others. According to the Centers for Disease Control, in the United States it is estimated that 1.25 million persons have chronic Hepatitis B and 4.9% of the U.S. population have been infected at some point. However hepatitis B is considered to be a vaccine preventable disease.
"It is imperative that laboratory professionals understand new methods in place for testing to detect and defend the public against life-threatening infectious diseases such as hepatitis. We are pleased that DiaSorin, with their many years of experience in research, development and manufacturing of in-vitro diagnostic testing for hepatitis A, B and C, is partnering with the NLTN to provide these hepatitis training programs," said Karen Breckenridge, Knowledge Manager for APHL's NLTN program. Hepatitis testing is performed to prevent further transmission to others and to defend communities against hepatitis outbreaks, and to identify those who require vaccination or to confirm immune status.
The final DiaSorin and NLTN co-sponsored training conference, "Understanding Hepatitis C" is scheduled for June 6, 2007. Faculty for the hepatitis conferences include Wendi L. Kuhnert, PhD, Centers for Disease Control, D. Robert Dufour, M.D., U.S. Department of Veterans Affairs, and Dawn Franzmeier, B.A., Product Manager, DiaSorin Inc. Contact NTLN via e-mail at nltnmarketingmgr@nltn.org , or visit www.nltn.org/courses or call 1-800-536-NLTN (6586) to register for any of the training sessions.
About DiaSorin
With corporate headquarters in Saluggia, Italy, and U.S. operations located in Stillwater, Minnesota, DiaSorin develops and manufactures over 300 disease state assays including infectious disease, blood virus, autoimmune, and bone and mineral metabolism. Please visit our website at www.diasorin.com for additional information.
Source: Business Wire
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CEL-SCI's Cel-1000 Shown to Significantly Enhance Immune Response Against Hepatitis B Antigen in Animals
http://biz.yahoo.com
VIENNA, Va., May 1 /PRNewswire-FirstCall/ -- CEL-SCI CORPORATION (Amex: CVM - News) announces that CEL-1000 alone increased the immune response against hepatitis B antigen, and that the combination of CEL-1000 with MAS-1, a proprietary water-in-oil adjuvant delivery system owned by Mercia Pharma, induced highly significant increases in specific anti-HBV (hepatitis B virus) antibodies. These findings were presented by Dr. Daniel Zimmerman, Senior Vice President of Research, Cellular Immunology at CEL-SCI at the 10th Annual Conference of the National Foundation for Infectious Diseases in Baltimore, Maryland.
This new finding with CEL-1000 may have broad application for the enhancement of immune responses by individuals who have a poor immune response to vaccinations. It also has application for antigen sparing (reducing the amount/dose of antigen) required for protective immunity, and application to biodefense and pandemic settings for anti-infectious vaccines.
Dr. Zimmerman said, "A good number of people, a great majority of them middle aged and older men, vaccinated against Hepatitis B fail to generate high enough levels of antibodies to be considered protected. These individuals need and deserve a better level of protection."
CEL-1000 has previously been shown to be protective in animal challenge studies against viruses and unrelated diseases, specifically herpes simplex virus, viral encephalitis and malaria. CEL-1000 appears to activate innate (very early stage) and Th1 type (cellular) immune responses to induce a broad- spectrum protection against infection in animal models. The innate immune system is generally accepted to be the first line of defense against infectious agents.
CEL-1000, derived from the beta chain of human MHC-II, is a modified version of a human immune-based protein known to bind to both human and mouse immune cells and appears to act by enhancing the host's protective immune response. More information on CEL-1000 is available at www.cel-sci.com.
CEL-SCI Corporation is developing new immune system based treatments for cancer and infectious diseases. The Company has operations in Vienna, Virginia and Baltimore, Maryland. The Company's lead product Multikine® is cleared to enter a global Phase III clinical trial in advanced primary head and neck cancer patients in the U.S. and Canada. CEL-SCI's other products, which are currently in pre-clinical stage, have shown protection against a number of diseases in animal tests and are being tested against diseases associated with bio-defense and avian flu.
Source: CEL-SCI Corporation
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May 2nd, 2007
HCV patients survival after liver transplantation is not improving
http://www.eurekalert.org
Transplant patients without HCV are doing better than ever
For liver transplant recipients without hepatitis C (HCV), survival has improved over time. However, for recipients with HCV, survival has not improved, according to a study in the May issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience at http://www.interscience.wiley.com/journal
/livertransplantation.
HCV-induced liver disease is the most common reason for liver transplantation in the U.S., however, previous studies have shown that these patients do not respond as well to liver transplantation. The difference has become even more striking in recent years, leading some to suggest that survival rates have been decreasing for patients with HCV who have received transplants.
Researchers led by Paul Thuluvath of The Johns Hopkins School of Medicine in Baltimore, MD, sought to study a large sample of the liver transplant population to determine if there has indeed been a decline in survival among HCV patients after adjusting for possible confounding factors.
They gathered data from the United Network for Organ Sharing on all adult liver transplantation performed in the U.S. between January 1991 and October 2001. They included 5,708 HCV patients and 16,116 non-HCV patients and performed multivariate analysis to determine the impact of confounding factors on survival.
The proportion of liver transplant patients with HCV increased dramatically over the study time period, from 16.4 percent in 1991 to 54.7 percent in 2001. However, patients with HCV had a lower 3-year survival (78.5 percent) compared to non-HCV patients (81.7 percent.) For the former group, there was no improvement in survival during the study period, in contrast to the latter group.
"In summary, the survival of patients transplanted with HCV is significantly lower than those without HCV," the authors report. "There has been a statistically significant improvement in patient and graft survival for non-HCV recipients between 1991 and 2001, but for HCV recipients, the survival rate has remained unchanged without any obvious explanations."
Another article in the same issue of Liver Transplantation by Luca Belli of Niguarda Hospital in Milan includes observations from another group of HCV positive patients who received liver transplants between January 1990 and December 2002. They noted a trend for better patient survival in recent years, "but the cumulative probability of developing severe recurrent disease remained unchanged," the authors report. They pinpointed the combination of a female recipient receiving an old graft as a strong risk factor for a severe recurrence.
An accompanying editorial by Marina Berenguer of Hospital La Fe in Valencia, Spain considers the conflicting data from these studies and others that came before and suggests that advanced donor age together with steroid pulse therapy and over immunosuppression can explain differences in outcomes. "The association with worse outcomes in recent years, and the controversy that seems to surround this observation, is likely due to differences in distribution of these variables from study to study, from center to center, and from year to year."
For future studies, she suggests that researchers use large databases to identify trends in liver transplantation, or that they perform studies comparing different management strategies. In the absence of effective antivirals, she concludes, "we are obliged to make sure through a better understanding of factors associated with outcome that we are minimizing harm to patients with our current management strategies."
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Article: "Trends in Post-Liver Transplant Survival in Patients With Hepatitis C Between 1991 and 2001 in the United States" Thuluvath, Paul; Krok, Karen; Segev, Dorry; Yoo, Hwan; Liver Transplantation; May 2007; (DOI: 10.1002/lt.21123).
Accompanying Article: "Liver Transplantation for HCV Cirrhosis: Improved Survival in Recent Years and Increased Severity of Recurrent Disease in Female Recipients: Results of a Long Term Retrospective Study" Belli, Luca; Burroughs, Andrew; Burra, Patrizia; Alberti, Alberto; Camma, Calogero; Samonakis, Dimitrios; Cillo, Umberto; Quaglia, Alberto; Boninsegna, Sara; Pinzello, Giovambattista. Liver Transplantation; May 2007; (DOI: 10.1002/lt.21093).
Editorial: "Recurrent Hepatitis C: Worse Outcomes Established, Interventions Still Inadequate" Berenguer, Marina. Liver Transplantation; May 2007; (DOI: 10.1002/lt.21136).
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Anadys Presents Results From Its NS5b HCV Program at International Conference on Antiviral Research
http://www.pr-inside.com
SAN DIEGO, May 2 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. described its optimization of a series of non-nucleoside compounds that potently inhibit the HCV NS5b polymerase enzyme during a podium presentation at the 20th International Conference on Antiviral Research (ICAR) in Palm Springs, CA today at 3:30 p.m. PDT (6:30 p.m. EDT).
Anadys reported optimizing NS5b polymerase inhibitors with nanomolar potency in both biochemical and replicon assays and with promising metabolic properties.
"Our work in our AN 025-1 program has led to several proprietary, non- nucleoside compounds with excellent potency against
the NS5b polymerase, a key enzyme necessary for the production of new HCV RNA in infected cells," said Lawrence C. Fritz, Ph.D., president and chief executive officer of Anadys Pharmaceuticals. "We are especially excited about the progress we have made in recent months in this HCV direct antiviral program and look forward to nominating a candidate this year from the ANA59X sub-series for clinical development as an orally-administered drug."
Background
HCV is a leading cause of chronic liver disease. Current therapies for genotype 1 HCV, the most common form of HCV, are associated with sub-optimal response rates and debilitating side effects. There remains an urgent need for the development of more effective and well-tolerated HCV treatments.
Methods
Anadys' researchers sought to discover small-molecule, non-nucleoside inhibitors of the HCV genotype 1 polymerase. The use of structure-based drug design methods facilitated investigation of a series of chemical classes. Systematic exploration of variations of the structures of the compounds resulted in a number of compounds that inhibit the NS5b enzyme with low nanomolar potencies. Knowledge of the parameters that provide potency facilitated work to explore other parameters, such as metabolic stability in vitro and pharmacokinetic behavior in animals.
"Our researchers have had considerable success in using structural data to guide our medicinal chemistry," said Devron R. Averett, Ph.D., chief scientific officer of Anadys. "Anadys' knowledge in this area has led us to attractive compounds that combine improved inhibitory potency against the genotype 1 NS5b enzyme with promising metabolic characteristics."
AN 025-1 Series
In 2007, Anadys expects to nominate a new preclinical candidate from the ANA59X sub-series of Anadys' AN025-1 program, a series of non-nucleoside NS5B polymerase inhibitors, for the treatment of chronic HCV infection. Non- nucleoside polymerase inhibitors are an example of direct antivirals. Direct antivirals act against the hepatitis C virus itself in contrast to immunomodulators which activate the body's immune system to attack the virus. The NS5b polymerase is a virally encoded enzyme essential to replication of HCV in the body. Anadys has identified a specific site on this enzyme that we believe is preferred as a drug target. Within the AN 025-1 program the Company has identified non-nucleoside compounds that bind to this specific location. These compounds directly inhibit replication of HCV in laboratory experiments at concentrations that Anadys believes will be achievable in humans. Anadys has optimized multiple characteristics of these compounds in order to identify a pre-clinical candidate to develop as an orally administered drug.
Hepatitis C Virus
There is currently no vaccine available to prevent the spread of HCV. The World Health Organization (WHO) reports that an estimated 170 million persons are chronically infected globally with HCV and 3 to 4 million persons are newly infected each year. Cirrhosis develops in about 10-to-20 percent of persons with chronic infection, and liver cancer develops in 1-to-5 percent of persons with chronic infection over a period of 20-to-30 years. Most patients suffering from liver cancer who do not have hepatitis B virus infection have evidence of HCV infection. The mechanisms by which HCV infection leads to liver cancer are still unclear. In the US, the National Institutes of Health estimate that HCV results in 10,000 to 12,000 deaths annually. The Center for Disease Control and Prevention estimated that the number of deaths could increase to nearly 40,000 by 2010. Hepatitis C also exacerbates the severity of underlying liver disease when it coexists with other hepatic conditions.
According to industry analyst reports and available market data, 3.2 million people are infected with HCV in the United States with only about 100,000 patients in the U.S. receiving treatment annually. Even so, it is estimated that annual U.S. sales of HCV treatments are approximately $3.5 billion. The total U.S. sales of HCV therapies are expected to continue to grow significantly as better therapies that provide greater efficacy and better tolerability become available.
About Anadys
Anadys Pharmaceuticals, Inc., http://www.anadyspharma.com/, is a biopharmaceutical company committed to advancing patient care by discovering, developing and commercializing novel small molecule medicines for the treatment of viral diseases and cancer. The Company's programs focus on Toll-Like Receptor-based small molecule product candidates and direct antiviral compounds that inhibit key steps in viral proliferation. The Company has core expertise in medicinal chemistry coupled with structure-based drug design, and is developing compounds for the treatment of hepatitis C infection, hepatitis B infection and cancer.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to the expected timing and plans for nominating a compound from the ANA59X sub-series, the believed potency and metabolic characteristics of compounds in Anadys' AN 025-1 program and references to the expected market growth and commercial opportunities for HCV therapies. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. In particular, the results of in vitro studies and initial clinical trials may not be predictive of future results, and Anadys cannot provide any assurances that any of its product candidates will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by risks related to its collaborative relationships with Novartis and LG Life Sciences, competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, the level of effort that its collaborative partners devote to development and commercialization of its product candidates, difficulties or delays in its pre-clinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments involving future products and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2006. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Source: Anadys Pharmaceuticals, Inc.
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Florida Celebrates National Hepatitis Awareness Month
http://www.emaxhealth.com
Hepatitis Awareness Month
The Florida Department of Health celebrates the first day of National Hepatitis Awareness Month with Hepatitis Day at the Capitol.
The purpose of the event is to promote hepatitis awareness and education, as well as encourage hepatitis testing, vaccination and prevention methods.
Hepatitis is characterized by inflammation of the liver. Hepatitis A, B and C are the most common types of viral hepatitis in the United States. Symptoms of hepatitis, if they are present, include nausea, fever, weakness, loss of appetite and jaundice. The Centers for Disease Control and Prevention (CDC) has issued guidance on an initiative to eliminate hepatitis B in the United States.
"The Bureau of Immunization and the Bureau of HIV/AIDS Hepatitis Prevention Program are working together to provide over 17,000 additional doses of hepatitis B (HBV) vaccine to at-risk adults," DOH Deputy State Health Officer Bonita Sorensen M.D., M.B.A. said. "Public health in Florida has already done a commendable job of significantly reducing hepatitis B in infants, children and adolescents. Here is our opportunity to do the same for adults who are at risk."
Most county health departments throughout Florida offer free hepatitis vaccine and testing to adults at risk. During Hepatitis Awareness Day at the Capitol, the Leon County Health Department provided free hepatitis B and free hepatitis A (HAV) vaccines to adults. There is no vaccine for hepatitis C (HCV).
Almost four million Americans and more than 300,000 Floridians are infected with the hepatitis C virus. Hepatitis C is referred to as the 'silent epidemic' because most people are unaware they are infected due to a lack of symptoms. The disease often lies undetected for 20-30 years and is a leading cause of liver cirrhosis and liver failure.
Hepatitis C is usually spread through contact with blood containing the virus. All individuals infected with HCV should be vaccinated for HAV and HBV, as both viruses can cause further liver damage. Hepatitis A is transmitted by eating food or drinking water that has been contaminated with human waste (feces). Hepatitis B is spread through contact with the blood or body fluids of an infected person.
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Hepatitis spread to patient in dental office
http://news.yahoo.com
NEW YORK (Reuters Health) - Hepatitis B virus was transmitted from one patient to another when they both underwent oral surgery in the same office, on the same day -- despite proper infection control measures -- public health officials report.
The situation came to light when a 60-year-old woman sought medical care because of joint pain and fatigue, and was found to have hepatitis B. She had no traditional risk factors for hepatitis, but she said she had oral surgery several months earlier.
A cross-match of the state department of health's hepatitis B registry found a patient infected with hepatitis B virus who had oral surgery a couple hours earlier that day.
Viral DNA from the two subjects was identical, according to Dr. John T. Redd, from the Centers for Disease Control and Prevention in Atlanta. .
An inspection of the surgeon's office showed that appropriate, standard precautions for preventing transmission of blood-borne viruses were being followed, the investigators report in the Journal of Infectious Diseases.
Hepatitis B virus can persist in dried blood on surfaces for a week or longer, and can also be present on surfaces that have no detectable blood.
Infection control procedures have nearly eliminated its spread in health care settings, note Dr. Ban Mishu Allos and Dr. William Schaffner in an accompanying commentary. Still, several similar cases have been reported in which the means of transmission could not be identified, they add.
This is "troubling because it suggests that there are aspects of transmission of bloodborne disease that remain poorly understood," according to the editorialists, from Vanderbilt University School of Medicine in Nashville, Tennessee.
They advocate universal hepatitis B vaccination of all adults up to 40 years of age, as well as thorough investigations for non-traditional exposure sources when hepatitis B virus is diagnosed in patients with no recognizable risk factors.
SOURCE: Journal of Infectious Diseases, May 1, 2007.
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Nucleonics Receives FDA Clearance to Begin Phase 1 Trial of Expressed RNAi Approach to Treating Chronic Hepatitis B Infections
http://biz.yahoo.com
Systemic Delivery of DNA Encoding Four shRNA Molecules Mediates Destruction of All HBV RNAs
HORSHAM, Pa.--(BUSINESS WIRE)--Nucleonics, Inc., a biotechnology company focused on the development of novel expressed interfering RNA (eiRNA) based therapeutics, announced today that it has received clearance from the US Food and Drug Administration for its Investigational New Drug (IND) application to begin a Phase 1 human safety study of Nucleonics' investigational eiRNA therapy for the treatment of chronic hepatitis B (HBV) infection. This clearance paves the way for the company to begin treating patients in June.
A total of 15 patients will be enrolled in the study, which will be conducted in the United States and Europe.
"We are very pleased to be able to move forward with this human safety study, which will be the first systemic delivery of an RNAi therapeutic to patients," said Robert Towarnicki, Nucleonics, Inc. president and chief executive officer. "Our approach, which simultaneously targets four different regions of the HBV genome, offers the opportunity to destroy all of the different RNA molecules produced by HBV within an infected cell through RNA interference. Therefore, if successful, it could offer a significantly more potent antiviral therapy than has ever before been achieved."
About Nucleonics HBV Candidate
Nucleonics employs an expressed interfering RNA (eiRNA) approach whereby scientists insert plasmid DNA coding for relevant short hairpin RNAs (shRNA) into targeted cells, inducing the cells to produce and deliver specific shRNA sequences. Nucleonics' researchers have shown the ability of shRNA produced in this way to silence genes, including Hepatitis B, Hepatitis C, and HIV, in relevant cell lines for extended periods of time. Moreover, they have silenced multiple genes in adult mice without triggering an interferon response. Nucleonics' product pipeline includes eiRNA therapeutics directed against chronic Hepatitis B, Hepatitis C, pan-influenza (including H5N1 avian flu), as well as prostate and ovarian cancer.
The Nucleonics' HBV clinical candidate encodes four short hairpin RNA (shRNA) molecules, each under the control of an RNA polymerase III promoter. Each of the four shRNAs targets a different segment of the HBV genome and collectively they mediate the destruction of all the different RNA molecules produced by HBV within an infected cell through RNAi. Extensive characterization of this vector has shown that each shRNA contributes significantly to the potent antiviral effect of the vector in infected cells. Moreover, the ability to provide four different shRNAs from a single expression vector greatly reduces the potential for viral resistance to develop.
About Nucleonics, Inc.
Nucleonics, founded in January 2001, is an emerging biotechnology company focused on the development of novel RNA interference-based therapeutics for viral and other diseases. Privately owned Nuc | 
