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Week Ending: November 2nd , 2007
Alan Franciscus
Editor-in-Chief
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This Issue:
October 27th, 2007
Hepatitis called 'silent epidemic' in Hawaii
http://the.honoluluadvertiser.com
By Greg Wiles
Advertiser Staff Writer
Calling hepatitis B and C a "silent epidemic" in Hawai'i, organizers of a symposium set for today aim to shed more light on the diseases and get more physicians and patients to acknowledge their threat.
The gathering at the Queen's Conference Center between 8 a.m. and 4 p.m. will feature perspectives on hepatitis from doctors, patients, insurance companies and others who deal with the diseases, which can lead to more serious health problems, including cirrhosis of the liver and liver cancer.
"There's a big problem with hepatitis here," said Dr. Alan Tice, an associate professor at the University of Hawai'i's John A. Burns School of Medicine.
"A lot of people aren't aware how big it is."
Tice said Hawai'i's population probably has higher risk because of greater numbers of people here from Asia and Pacific Islands, where rates are higher than those found in the United States. Rates in those regions range from 7 percent of the population to 20 percent, according to the Hepatitis Support Network of Hawaii.
Hepatitis also can show up in former drug users who've shared needles, people who've been tattooed with dirty instruments or those who've shared razors or toothbrushes, Tice said. The incubation period for the diseases can be more than 10 years.
Tice said hepatitis C can be treated successfully in two-thirds of the cases if detected early enough, while hepatitis B can be knocked down.
The symposium is being sponsored by the Hepatitis Support Network of Hawaii. Ken Akinaka, executive director of the group, said they hope to raise awareness of hepatitis among physicians and the public.
"We really want to educate medical providers and the public at large about the silent epidemic," Akinaka said.
Reach Greg Wiles at gwiles@honoluluadvertiser.com.
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October 29th, 2007
Ono and Medarex Announce Allowance of Investigational New Drug Application for Fully Human Anti-PD1 Antibody
http://biz.yahoo.com
Monday October 29, 4:00 pm ET
Addition of Hepatitis C Treatment to Ongoing Oncology Program for MDX-1106
PRINCETON, N.J., Oct. 29 /PRNewswire-FirstCall/ -- Ono Pharmaceutical Co., Ltd. and Medarex, Inc. (Nasdaq: MEDX - News) announced today the allowance of an investigational new drug application (IND) filed with the U.S. Food & Drug Administration (FDA) for MDX-1106 (ONO-4538: development code of Ono Pharmaceutical Co., Ltd.), a fully human anti-PD-1 antibody being investigated for the treatment of chronic viral infections, with the first trial to target hepatitis C. MDX-1106 was developed under the May 2005 collaborative research agreement between Ono and Medarex, and currently is in a separate ongoing Phase I clinical study in patients with recurrent or treatment- refractory cancer.
The new Phase I single-dose, dose-escalation trial with MDX-1106/ONO-4538 is expected to enroll up to 34 patients with active hepatitis C genotype 1 infection (HCV). The study is intended to evaluate the safety, pharmacokinetics, and preliminary efficacy of single doses of MDX-1106/ONO- 4538.
"Recently, involvement of PD-1 in hepatitis C has been reported in the scientific literature," said Shozo Matsuoka, Ph.D., Senior Managing Director of Ono Pharmaceutical, Co., Ltd. "ONO-4538/MDX-1106 aims to improve the immune capacity of the body and treat hepatitis C with a novel mechanism of action which inhibits the involvement of PD-1. We are seeking to develop ONO- 4538/MDX-1106 to be a new treatment for hepatitis C."
"We value our partnership with Ono and are pleased with the progress to study the potential of MDX-1106 in both oncology and infectious diseases," said Howard Pien, President and CEO of Medarex. "We believe that our ongoing program in patients with cancer is currently progressing well and that this exploratory Phase I study in HCV may be a step toward potentially adding new infectious disease indications for therapeutic blockade of this important T cell regulatory molecule."
About MDX-1106/ONO-4538
PD-1 (programmed cell death 1) is one of the receptors expressed on the surface of activated lymphocytes (T-cells) and is involved in the system of negative regulation for the suppression of activated lymphocytes. An increasing number of studies have reported that tumor cells and certain chronic viruses, including HCV, may use the PD-1 pathway to evade host adaptive immune responses (which protect the host from both harmful pathogens and tumors), suggesting that blockade of the negative regulatory signal mediated by PD-1 may promote the host immune response to recognize tumor cells as foreign and eliminate viral pathogens. Preclinical studies suggest that blockade of the PD-1 signaling pathway by MDX-1106/ONO-4538, a fully human anti-PD-1 antibody, activates T-cell responses and promotes an immune response to fight tumors and infectious diseases. Medarex and Ono Pharmaceutical continue to investigate the potential of MDX-1106/ONO-4538 for cancer in an ongoing Phase I clinical trial and for hepatitis C.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb® technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. More than 30 of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with seven of the most advanced product candidates currently in Phase III clinical trials. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs. For more information about Medarex, visit its website at www.medarex.com.
Medarex Statement on Cautionary Factors
Except for the historical information presented herein, matters discussed herein may constitute forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words "potential"; "plan"; "expect"; "may"; or similar statements are forward-looking statements. Medarex disclaims, however, any intent or obligation to update these forward- looking statements. Risks and uncertainties include risks associated with product discovery and development, uncertainties related to the outcome of clinical trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of MDX-1106 in patients, uncertainties related to product manufacturing, as well as risks detailed from time to time in Medarex's public disclosure filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2006 and subsequent Quarterly Reports on Form 10-Q. There can be no assurance that such development efforts will succeed or that other developed products will receive required regulatory clearance or that, even if such regulatory clearance were received, such products would ultimately achieve commercial success. Copies of Medarex's public disclosure filings are available from its investor relations department.
Medarex®, the Medarex logo and UltiMAb® are registered trademarks of Medarex, Inc. All rights are reserved.
Source: Medarex, Inc.
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Homelessness increases risk of infection for injecting drug users
http://www.news-medical.net
A new report from the Health Protection Agency shows that around three-quarters of injecting drug users (IDUs) have been homeless at some point. In addition, those who have been homeless have higher levels of injecting risk and associated infections, primarily through the sharing of needles and low standards of hygiene.
The report, 'Shooting Up: Infections Among Injecting Drug Users in the UK', suggests that homeless people who inject drugs are more likely to share needles and syringes: One in four IDUs who reported being homeless in the past year said that they had shared needles and syringes in the last month, compared with one in six who had not been homeless. Sharing needles seriously increases the risk of getting life threatening infections such as hepatitis C and HIV.
IDUs are also more likely to develop abcesses, wounds and bacterial infections such as MRSA. Increasing numbers of IDUs inject in the groin and inject crack-cocaine, which both carry a higher risk of infection.
Almost half of IDUs are infected with hepatitis C, and one in four has been exposed to hepatitis B. However, the number of IDUs in contact with drug services has increased noticeably in recent years and hepatitis B vaccination uptake has risen, with two-thirds of all IDUs reporting taking at least one vaccine dose. Overall one in 75 IDUs in the UK has HIV. In London however, one in every 20 IDUs is infected with HIV.
Dr Fortune Ncube , one of the Agency's experts in blood borne viruses, who compiled the report said: "Injecting drug users who are also homeless are likely to find it harder to maintain hygienic injection practices as a result of having to inject in public places or having difficulty in storing injecting equipment somewhere clean. Injecting drug users in this situation are more susceptible to contracting severe life-threatening infections, as are those IDUs who inject into the groin or inject crack cocaine.
"The recent increase in infections among IDUs indicates a need to re-examine the scope and range of harm reduction services provided for IDUs. Although a lot of work has been done in response to this, such as recent NICE guidelines and National Clinical Guidelines, much more is still needed to bring the levels of infection down."
Notes:
- To see the full report please go to http://www.hpa.org.uk/publications/
PublicationDisplay.asp?PublicationID=105
- For further information, contact the Health Protection Agency, Colindale press office on 020 8327 6690/7097/6055/7098.
- A recent estimate of the numbers of injecting drug users in the UK suggests 140,000 injectors of heroin and crack-cocaine in England , (0.42% in the 15-64 age group).
- IDUs' experience very high levels of infection, up to 80% of those acquiring hepatitis C develop chronic infection and are at risk from developing cirrhosis and liver cancer.
- Between 1992 and 2006 there were 62,424 laboratory reported diagnoses in England ; 90% of these diagnoses gave injecting drug use as the route of infection.
- Transmission of both hepatitis B and hepatitis A continues among IDUs even though there is an effective vaccine for both conditions, proportional uptake of hepatitis B vaccination has increased markedly in recent years.
- IDUs are members of wider communities and infection among this group may have impact on other community members such as family members, sexual partners and healthcare workers.
- 'Shooting Up: Infections Among Injecting Drug Users in the United Kingdom 2006' has been produced in collaboration with Health Protection Scotland, National Public Health Service for Wales , Communicable Disease Surveillance Centre Northern Ireland , and Centre for Research on Drugs & Health Behaviour, London School of Hygiene and Tropical Medicine. The report incorporates data from the Agency's Unlinked Anonymous Prevalence Monitoring Programme (UAPMP) together with laboratory reports of infections and data from cohort studies in IDUs. The Unlinked Anonymous Prevalence Monitoring Programme's (UAPMP) aims to measure the distribution of infection in sub-groups of the adult population, monitor HIV, hepatitis B and hepatitis C in those injectors in contact with specialist services, such as needle exchanges, or on treatment programmes, such as methadone maintenance.
- For current advice on the immunisation of injecting drug users please refer to The 'Green book' via www.immunisation.nhs.uk.
http://www.hpa.org.uk
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Efficacy, safety, and changes in angiogenic markers following sunitinib monotherapy in patients with advanced hepatocellular carcinoma: Experience from a phase II study: Abstract PR 7.
http://www.aacr.org
Use of sunitinib, designed to reduce tumor angiogenesis, appears to offer early evidence of antitumor activity for patients with a difficult to treat liver cancer known as advanced hepatocellular carcinoma (HCC), say researchers at Dana Farber Harvard Cancer Center.
Results from a 30-patient Phase II study in HCC of the agent, which is approved for use in kidney and rare stomach cancers, show that cancer stabilized in 10 patients for at least three months while one patient had a partial response. Overall, the agent offered a progression-free survival of four months, says the study's lead investigator, Andrew X. Zhu, M.D., Ph.D., an attending oncologist at Massachusetts General Hospital Cancer Center and an assistant professor of medicine at Harvard Medical School.
"We have seen preliminary evidence of anti-tumor activity, and although it is modest, it is also encouraging because all of these patients have cancer that cannot be removed by surgery or which has metastasized," Dr. Zhu said. "This is a small, single arm study so there is need for more research to confirm this potential benefit, and to examine safety more closely." The treatment was generally well tolerated in most patients, Dr. Zhu says, but adds that grade three and four toxicities were observed in approximately three to 20 percent of patients, depending on the specific side effect.
HCC is most commonly found in patients with chronic viral hepatitis (B or C) or with cirrhosis, and surgery to remove tumors is only possible in a small percentage of patients. Generally, patients have a poor prognosis because these tumors produce a lot of proteins, such as VEGF and VEGFR2, that make them highly vascular and able to build a solid and nurturing blood supply with increased ability to invade surrounding major vessels and to metastasize, Dr. Zhu says. Sunitinib is a receptor tyrosine kinase inhibitor designed to target and block VEGFR2 activity, among other pro-growth molecules.
To find out if sunitinib could target HCC, the research team employed a number of research tools to measure changes in the patients' blood and tumor perfusion. "Instead of just trying to determine if the drug is attacking the tumor, we want to get a sense of what kind of changes the agent might be inducing," Dr. Zhu said. "We want to know what the mechanisms are that might confer benefit as well as toxicity."
The team used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess changes in the permeability of tumor blood vessels and found that it decreased by an average of 38 percent after two weeks of sunitinib therapy. Using protein arrays to test for angiogenic biomarkers in the blood, the investigators found that the levels of VEGF and PIGF increased, while that of soluble VEGFR2 declined in most patients. Also, flow cytometry analyses of blood cells suggested that circulating endothelial cells increased in some patients while circulating progenitor cells were significantly decreased, indicating that sunitinib may indeed target key angiogenesis pathways in relevant cell populations.
"These are very interesting changes in blood markers induced by sunitinib. Ongoing studies of these and of other markers might help us to understand how the drug works in HCC and what changes might be relevant in predicting the potential clinical benefits in these patients," Dr. Zhu said.
The HarvardMedicalSchool research team involved in this study includes Dushyant Sahani, M.D., and Rakesh K. Jain, Ph.D. The study was funded by Pfizer, Inc., manufacturers of sunitinib (marketed as Sutent).
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October 30th, 2007
Inovio Biomedical's DNA Vaccine Delivery Technology Moves Ahead in Clinical Trial for Hepatitis C
http://biz.yahoo.com
SAN DIEGO--(BUSINESS WIRE)--Inovio Biomedical Corporation (AMEX:INO - News), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today that its partner, Tripep AB of Sweden, has begun enrolling patients for its Phase I/II clinical study of a novel DNA vaccine designed to treat chronically infected hepatitis C virus (HCV) patients. The trial will test Tripep’s proprietary DNA vaccine, ChronVac-C®, administered using Inovio’s MedPulser® DNA Delivery System, in 12 subjects already infected with HCV. The trial is being conducted in Sweden at the world-renowned Karolinska Institute.
The main purpose of the study is to show that the treatment is safe, but also to test if the treatment boosts patients’ immune response to hepatitis C and its effects on virus replication. The market for therapies against hepatitis C infections is estimated at more than $2 billion and is expected to grow to more than $8 billion by 2015.
“This is the first human study in the world in which a DNA vaccine against an infectious disease is being administered by in vivo electroporation. We are enthusiastic that enrollment has started as planned,” said Jan Nilsson, CEO of Tripep AB.
Dr. Avtar Dhillon, Inovio's president and CEO, said: "Inovio is pleased to reach this important clinical milestone. Because hepatitis C infections are responsible for a high incidence of debilitating liver disease and liver cancers each year, we are pleased the trial is moving forward rapidly. In addition, Tripep’s hepatitis C DNA vaccine trial marks our fifth partnered clinical trial using Inovio’s proprietary non-viral DNA delivery technology.”
The study encompasses a total of 12 treatment naive patients with chronic hepatitis C virus infections of genotype 1 and with a low viral load. The patients will be divided into four dose groups. Each patient will receive four monthly vaccinations and then be monitored for another six months.
About Inovio’s DNA Vaccine Technology
DNA vaccines have the potential to by-pass inherent scientific obstacles of conventional vaccines that prevent their development for cancer and chronic infectious diseases such as HIV and hepatitis C. Pre-clinical data has indicated the ability of Inovio’s technologies to effectively deliver and significantly enhance the potency of such immunotherapies without the potential safety concerns of viral delivery systems.
Inovio’s DNA-based immunotherapy products consist of DNA plasmids and electroporation-based DNA delivery systems. DNA plasmids are designed to express (produce) antigens that can induce an immune response specific to a cancer or infectious disease-causing organism. These plasmids are created synthetically and readily manufactured using well-established bacterial fermentation and purification technology. After a plasmid is delivered into muscle or tumor cells, production of the desired antigens may induce a preventive or therapeutic immune response against the intended disease. Inovio’s advanced electroporation devices facilitate delivery and expression of DNA vaccines to produce the desired antigens. Primate and/or interim Phase I data has have shown significantly enhanced antibody and T-cell immune responses relative to plasmid DNA delivered by other methods, suggesting the potential to provide better preventive or therapeutic effects against complex infectious diseases and cancers.
Inovio is poised to deliver advanced DNA-based vaccines and immunotherapies, devices and know-how in this rapidly advancing field. The company is actively licensing its technology to pharmaceutical and biotechnology companies and supporting early stage clinical studies arising from its own research efforts or through academic collaborations.
About Hepatitis C and ChronVac-C
Hepatitis is a disease characterized by inflammation of the liver. Hepatitis C virus (HCV) is spread primarily by direct contact with human blood, the major causes worldwide being the use of unscreened blood transfusions and re-use of inadequately sterilized needles and syringes. As many as 70% - 90% of newly infected patients may progress to develop chronic infection (WHO: 2002). Of those with chronic liver disease, 5% - 20% may develop cirrhosis. About 5% of infected persons may die from the consequences of long term infection (due to liver cancer or cirrhosis). Globally, an estimated 170 million people are chronically infected with HCV, representing a reservoir sufficiently large for HCV to persist, and 3 to 4 million persons are newly infected each year. In the US, while new incidences of HCV have dropped dramatically, an estimated 4.1 million Americans have been infected with HCV, of whom 3.2 million are chronically infected (Centers for Disease Control and Prevention: 2006).
HCV infections in the liver do not trigger an immune response very effectively. Certain antiviral therapies, while expensive, are somewhat effective in treating hepatitis C. There is no vaccine currently available to prevent hepatitis C. ChronVac-C(R) is designed to be a therapeutic DNA vaccine that can stimulate the body's immune system. Animal experiments demonstrated that ChronVac-C vaccination activated B-cells and T-cells (the latter being regarded as the most significant to clearing the chronic infection relating to hepatitis C) that killed cells producing HCV protein. In humans, the ChronVac-C DNA plasmid will be injected into muscle tissue, where vaccinations are usually given, and taken up by muscle cells with the assistance of Inovio's electroporation-based DNA delivery system. These muscle cells would be expected to then produce predetermined antigens that may activate the body's immune system to attack all cells producing HCV proteins.
About Tripep AB
Tripep AB is a Swedish biotechnology research company that develops and commercializes candidate drugs based on patented and proprietary technologies. Its main focuses are research and clinical development of ChronVac-C(R), a therapeutic vaccine against hepatitis C; preclinical research focusing on the development of therapeutic and prophylactic vaccines against influenza A and HIV; and the RAS(R) technology platform. More information is available at www.tripep.se. Contact Jan Nilsson, CEO, at +46 8 449 8480 or jan.nilsson@tripep.se.
About Inovio Biomedical Corporation
Inovio Biomedical (AMEX: INO - News) is focused on developing multiple DNA-based immunotherapies and commercializing its Selective Electrochemical Tumor Ablation (SECTA) therapy. Inovio is a leader in developing human applications of electroporation, using brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical. Interim human data has shown that Inovio’s DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. The SECTA therapy for locally treating solid tumors is designed to selectively kill cancerous cells and minimize cosmetic or functional detriments often caused by surgical removal of predominantly healthy tissue typically treated around a tumor. Inovio’s technology is protected by an extensive patent portfolio covering in vivo electroporation. More information is available at www.inovio.com.
This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that pre-clinical results referenced in this release may not be indicative of results achievable from testing in humans and that results from one study may necessarily not be reflected or supported by the results of other similar studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio’s technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2006, our 10-Q for the six months ended June 30, 2007, and other regulatory filings. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, or that final results of clinical studies will be supportive of regulatory approvals required to market licensed products.
Contact:
Inovio Biomedical Corporation
Investor Relations:
Bernie Hertel, 858-410-3101
or
Media Relations:
Jeff Richardson, 805-491-8313
Source: Inovio Biomedical Corporation
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Vertex Expands Its Pipeline
http://www.fool.com
By Brian Lawler
Yesterday, Rule Breakers pick Vertex Pharmaceuticals (Nasdaq: VRTX) released its third-quarter financial results and updated investors on the progress with its pipeline.
The most interesting revelation from the conference call and earnings release was that Vertex is planning on advancing a second-generation protease inhibitor into the clinic by the end of 2007. This is a smart move, since viral resistance is likely to occur in some subset of patients infected with hepatitis C virus (HCV) and treated with its lead drug candidate telaprevir.
On the conference call, Vertex's management said it was looking to build a pipeline of anti-HCV products. However, it's not clear if this was just a comment about the second protease inhibitor, or an indication that Vertex would start developing compounds targeting the other steps of HCV life cycle, like polymerase inhibitors.
If Vertex is looking to build a portfolio of HCV-fighting drugs along the lines of Roche or Gilead Sciences (Nasdaq: GILD), then it's likely going to have to do the drug development work in-house rather than by signing partnership deals, as there are few unpartnered promising clinical stage HCV antiviral compounds available. Or it could just sign a deal for Flamel Technologies' (Nasdaq: FLML) improved interferon drug candidate.
If Vertex does develop drugs targeting different aspects of the hepatitis C virus and its second protease inhibitor treatment is successful, it will help to cement Vertex's leading role in antiviral drug development. There's also the possibility that Vertex's second protease inhibitor could be more potent or have fewer side effects than telaprevir. That's something that would keep the cash rolling in for a long time.
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Significant New Data on Roche's PEGASYS(R) and Hepatitis C Pipeline Compounds to be Featured at 58th Annual AASLD Meeting
http://biz.yahoo.com
NUTLEY, N.J., Oct. 30 /PRNewswire/ -- Roche today announced that new study results for PEGASYS® (peginterferon alfa-2a), the world's leading treatment for chronic hepatitis C virus (HCV) infection, as well as the company's robust pipeline of hepatitis C compounds in clinical development, will be presented at the upcoming 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting, in Boston, November 2-6, 2007.
The presentations will include final efficacy and safety results from REPEAT, a major study examining retreatment with PEGASYS/COPEGUS® (ribavirin) in patients whose infection did not respond to prior treatment with Peg-Intron® (peginterferon alfa-2b) and ribavirin. Additionally, the first efficacy and safety results from a Phase IIa study with the polymerase inhibitor R1626, as well as new data on the polymerase inhibitor R7128 (being developed in partnership with Pharmasset), and the protease inhibitor R7227/ITMN-191 (being developed with InterMune), will be presented.
"As the premier meeting in the science and practice of hepatology, The Liver Meeting provides Roche with an important opportunity to demonstrate our commitment to advancing the diagnosis and treatment of this devastating disease," said Nick Cammack, Ph.D., Virology Disease Biology Area Leader, Roche. "In addition to ongoing research with PEGASYS, reinforcing its status as the leading HCV therapy, Roche is dedicated to developing new molecules that could help more patients achieve treatment success."
PEGASYS Highlights
-- "Pegylated interferon alfa-2a plus ribavirin (RBV) in prior non-responders to pegylated interferon alfa-2b/RBV: final efficacy and safety outcomes of the REPEAT study," D. M. Jensen et al., Monday, November 5, 3:45 p.m. - 4:00 p.m. ET (Oral Presentation No. LB4).
-- "Rapid and early virological response rates are increased with 12 week 360 µg/wk peginterferon alfa-2a and standard ribavirin in HCV genotype 1 treatment naive patients: efficacy and safety analysis of the induction phase of the CHARIOT study," S. Roberts et al., Sunday, November 4, 6:00 p.m. - 6:15 p.m. ET (Oral Presentation No. 54).
-- "Prolonged Antiviral Therapy With Peginterferon to Prevent Complications of Advanced Liver Disease Associated With Hepatitis C: Results of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial," A. M. Di Bisceglie et al., Monday, November 5, 3:00 p.m. - 3:15 p.m. ET (Oral Presentation No. LB1).
-- "Association of Pre-Treatment and On-Treatment Factors with Rapid Virologic Response in HCV Genotype 1 Infected Patients Treated with PegIFN-2a/RBV," M. Rodriguez-Torres et al., Tuesday, November 6, 8:00 a.m. - 12:30 p.m. ET (Poster No. 1305).
-- "Prophylactic Peginterferon Alfa-2a/Ribavirin vs. No Prophylaxis Following Orthotopic Liver Transplantation (OLT) for Hepatitis C: 24- Week Virologic and Safety Responses," M. R. Charlton, et al., Sunday, Nov. 4, 3:00 p.m. - 3:15 p.m. ET (Oral Presentation No. 25).
Pipeline Highlights
-- "Robust Synergistic Antiviral Effect of R1626 in Combination with Peginterferon alfa-2a (40KD), with or without Ribavirin – Interim Analysis Results of Phase 2a Study," P. J. Pockros, et al., Tuesday, November 6, 2007, 9:00 a.m. - 9:15 a.m. ET (Oral Presentation No. 167).
-- "A high barrier to resistance may contribute to the robust antiviral effect demonstrated by R1626 in HCV genotype 1-infected treatment-naïve patients," S. Le Pogam et al., Tuesday, November 6, 2007, 8:00 a.m. - 12:30 p.m. ET (Poster No. 1298).
-- "Antiviral Activity, Pharmacokinetics, Safety, and Tolerability of R7128, a Novel Nucleoside HCV RNA Polymerase Inhibitor, Following Multiple, Ascending, Oral Doses in Patients with HCV Genotype 1 Infection Who have Failed Prior Interferon Therapy," R. Reddy et al., Tuesday, November 6, 2007, 8:00 a.m. - 12:00 p.m. ET (Poster No. LB9).
-- "Genotype Coverage of the HCV NS3/4A Protease Inhibitor ITMN-191 (R7227): Biochemical Data Reveals Potent Inhibition and Slow Dissociation with Genotype 1-6 Proteases," P. Rajagopalan et al., Tuesday, November 6, 2007, 8:00 a.m. - 12:30 p.m. ET (Poster No. 1386).
About PEGASYS
PEGASYS, in combination with COPEGUS (ribavirin), are indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).
PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.
Important Safety Information
PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
Alpha interferons, including PEGASYS® (Peginterferon alfa-2a), 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. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).
PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.
Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score .6) is observed.
The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%). Serious adverse events in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema). Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News and one of the Top 20 Employers (Science magazine). In 2006, Roche was ranked the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://rocheusa.com or www.roche.us.
All trademarks used or mentioned in this release are protected by law.
Source: Roche
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Schering-Plough Highlights PEGINTRON(TM) Clinical Data Presentations at the American Association for the Study of Liver Diseases (AASLD) 2007 Annual Meeting
http://www.examiner.com
KENILWORTH, N.J., Oct. 30 /PRNewswire-FirstCall/ -- Leading researchers will present 68 data presentations involving Schering-Plough's hepatitis products, including PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) combination therapy, a current standard of care in the treatment of chronic hepatitis C, at the 59th American Association for the Study of Liver Diseases (AASLD) Annual Meeting in Boston, Nov. 2-6.
Among these are several studies discussing the predictability of response with PEGINTRON and REBETOL and assessing how results at important treatment milestones early in the course of therapy can help physicians and patients make informed treatment decisions.
Researchers will present the final results from the POWeR (Peginterferon alfa-2b Prospective Optimal Weight-based Dosing Response) program, a large observational study involving nearly 2,000 patients conducted at academic and community clinics in Canada between 2002 and 2006. In the study, PEGINTRON and REBETOL combination therapy achieved consistent sustained virologic response (SVR) rates across patient weights and consistently low relapse rates in a "real-life" treatment setting.
Investigators also will present new data on the investigational use of low-dose PEGINTRON as maintenance therapy in chronic hepatitis C nonresponder patients with fibrosis or cirrhosis. The goal of maintenance therapy in this very hard-to-treat patient population is to prevent or delay the progression of liver disease.
Hepatitis C is the most common blood-borne infection in America and the most common form of liver disease, affecting nearly 5 million people in the United States and 200 million people worldwide.
For program information, please visit the American Association of Liver Disease Web site at www.aasld.org
Key PEGINTRON Presentations:
Predictability of Response
- Predictability of Response: Positive and Negative Predictive Values of Rapid and Early Virologic Responses to Peginterferon Alfa-2b and Ribavirin in the Treatment of Chronic Hepatitis C; F. Poordad et al., Abstract 305, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
- Ultra Rapid Virologic Response Predicts Sustained Virologic Response in HCV Infected Patients with Genotype 3 and High Viral Load: The Get-C Study; S. Pianko et al., Abstract 349, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
- Rapid Virological Response at Week 4 Is the Best Predictor of Treatment Outcome in Patients with Chronic Hepatitis C: A Multivariate Analysis; M. Martinot-Peignoux et al., Abstract 303, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
- Assessment of Both Virological Response at Week 4 and At Week 12 Optimizes Prediction of Treatment Outcome In Patients with Chronic Hepatitis C Treated with Peginterferon Alfa-2b Plus Ribavirin; M. Martinot-Peignoux et al., Abstract 304, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
- Viral Kinetics Can Quickly Predict Sustained Virological Response in HCV Patients with Normal ALT Treated with Pegylated Interferon Alfa-2b and Ribavirin: A Prospective Study; P. Deltenre et al., Abstract 312, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
PEGINTRON POWeR Study
- Final Results of the Canadian POWeR (Peginterferon Alfa-2b Prospective Optimal Weight-Based Dosing Response) Program: Sustained Virologic Response (SVR) To Weight-Based Peginterferon Alfa-2b plus Ribavirin in a Large, Mixed Community and Academic Observational Study; Paul Marotta et al., Abstract 254, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
- Consistency of Sustained Virologic Response (SVR) Across Weight Categories: Results from the Canadian POWeR (Peginterferon Alfa-2b Prospective Optimal Weight-Based Dosing Response) Program; S. Feinman et al., Abstract 302, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
- Response to Peginterferon Alfa-2b plus Ribavirin Combination Therapy in Genotype 2 and 3 Patients with Poor Baseline Prognostic Factors: Results of The Canadian POWeR Program; R. Bailey et al., Abstract 246, Saturday, Nov. 3, 2:00 pm, Exhibit Hall C
Low-Dose PEGINTRON Maintenance Therapy
- Tolerability of Low-Dose Peginterferon Alfa-2b in Hepatitis C Patients with Cirrhosis: Results from the COPILOT Trial; M. Shah et al., Abstract 1322, Tuesday, Nov. 6, 8:00 am, Exhibit Hall C
- Long-Term Low- Dose Treatment with Pegylated Interferon Alfa-2b Leads to a Significant Reduction in Fibrosis and Inflammatory Score in Chronic Hepatitis C Nonresponder Patients with Fibrosis or Cirrhosis; S. Kaiser, et al., Abstract 1311, Tuesday, Nov. 6, 8:00 am, Exhibit Hall C
Schering-Plough Sponsored CME Symposium
"Clinical Approaches to HCV Management: Community Cases, Expert Analysis" Monday, Nov. 5, 6:30-8:30 p.m., Sheraton Boston Hotel - Grand Ballroom and Liberty 39 Dalton Street, Boston
FACULTY:
Willis C. Maddrey, M.D. (Chair)
Professor of Internal Medicine and Executive Vice President for Clinical Affairs, The University of Texas Southwestern Medical Center at Dallas
Steven L. Flamm, M.D.
Associate Professor of Medicine and Medical Director, Liver Transplantation, Feinberg School of Medicine, Northwestern University, Chicago
John B. Gross, M.D.
Associate Professor of Medicine, Mayo Clinic College of Medicine Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minn.
Stephen Harrison, M.D.
Chief of Hepatology and Associate Program Director, GI Fellowship Brooke Army Medical Center, Fort Sam Houston, Texas
About PEGINTRON
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
Alpha interferons, including PEGINTRON and INTRON(R) A, 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 and/or INTRON A therapy.
Use with Ribavirin: Ribavirin may cause birth defects and/or death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with REBETOL therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.
Contraindications
PEGINTRON is contraindicated in patients with hypersensitivity to PEGINTRON or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6 [class B and C]) in cirrhotic CHC patients before or during treatment. INTRON A (Interferon alfa- 2b, recombinant) for Injection is contraindicated in patients with hypersensitivity to INTRON A or any component of the product, autoimmune hepatitis, and decompensated liver disease. PEGINTRON or INTRON A in combination with REBETOL therapy is additionally contraindicated in patients with hypersensitivity to ribavirin or any other component of the product, women who are pregnant, men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance less than 50 mL/min.
Avoid Pregnancy
REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients during therapy and 6 months post- treatment. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for 6 months after completion of therapy. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for 6 months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Incidence of Adverse Events
There are no new adverse events specific to PEGINTRON as compared to INTRON A; 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% of patients, which may decrease in severity as treatment continues. Application site disorders were common (47%), but all were mild (44%) or moderate (4%) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2% 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%) with PEGINTRON but similar to INTRON A (58%). Depression was most common at 29%. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1% of patients during or shortly after completing treatment with PEGINTRON.
The following serious or clinically significant adverse events have been reported at a frequency less than 1% 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% in the PEGINTRON/REBETOL groups compared to 14% in the INTRON A/ REBETOL group. The incidence of severe adverse events in the PEGINTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL group and 31-34% in the PEGINTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42% of patients receiving PEGINTRON (1.5 mcg/kg)/REBETOL and in 34% of those receiving INTRON A/REBETOL.
Additional Safety Information
Relapse of drug addiction/overdose has occurred in patients on PEGINTRON therapy. Aggressive behavior sometimes directed towards others has occurred in patients with and without a previous psychiatric disorder during PEGINTRON and/or INTRON A treatment and follow-up. If patients develop psychiatric problems, including clinical depression, it is recommended that patients be carefully monitored during treatment and in the 6-month follow-up period. If psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is identified, it is recommended that treatment with PEGINTRON and/or INTRON A be discontinued, and the patient be carefully followed with psychiatric intervention, as appropriate. Cases of encephalopathy have been observed in some patients, usually elderly, treated with higher doses of PEGINTRON and/or INTRON A. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alpha therapies, including PEGINTRON and INTRON A. Dental and periodontal disorders have been reported in patients receiving PEGINTRON or INTRON A in combination with REBETOL therapy.
For full prescribing information, please see the PEGINTRON Package Insert at www.pegintron.com
About Schering-Plough
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 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 market for 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 and a discussion of risks and uncertainties that may impact forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Part II, Item 1A, "Risk Factors" in the company's third quarter 2007 10-Q.
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October 31st, 2007
The Next Hepatitis C Blockbuster?
http://www.fool.com
By Brian Lawler
On Friday, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) convenes, and several drug developers -- from Roche to smaller development-stage participants such as Pharmasset (Nasdaq: VRUS) -- will present data on their lead compounds for treating hepatitis C.
It's an exciting time to follow the hepatitis C treatment space, since there have never before been so many new compounds in development for the disease. With so many compounds to sift through, we can look at the leading drug candidates that may play a role in changing how the hepatitis C virus (HCV) will be attacked.
The leaders
Right now, most patients infected with the genotype 1 HCV -- the most common subtype of HCV in North America and Europe -- are treated with an interferon-based therapy consisting of either Schering-Plough's (NYSE: SGP) PEGINTRON or Roche's Pegasys.
Only about half of the genotype 1-infected patients who are treated with these standards of care, in combination with ribavirin, achieve a sustained virologic response, meaning they show no signs of HCV in their blood six months following treatment.
Having no signs of HCV at any time during a course of treatment means a patient has undetectable viral loads. When patients achieve undetectable viral loads, it could indicate the possibility of a sustained virologic response and, perhaps, ultimately being cured of the disease.
The future of HCV treatment will almost assuredly consist of a combination of an interferon and an oral antiviral drug. More than a dozen oral antivirals are in various development stages, ranging from Abbott Labs' (NYSE: ABT) preclinical-stage protease inhibitor to Vertex Pharmaceuticals' (Nasdaq: VRTX) phase 2 candidate, telaprevir.
Here are the leaders in efficacy and stage of clinical development in the race to become the first oral antiviral hepatitis C treatment on the market.
*Study results in genotype 1 HCV patients and all combination study results include the use of ribavirin.
All the compounds above that have enough data to date show incredible improvements in undetectable viral loads (if the data holds up over longer testing), versus about half of the patients who achieve a sustained virologic response from PEGINTRON or Pegasys therapy alone.
Still, it's not all gravy for the anti-HCV drugs in the table: Every single compound except the Pharmasset drug (which has not been tested in patients very long) has shown side effects, such as a rash with telaprevir, gastrointestinal problems with boceprevir, neutropenia with R1626, and high liver enzyme levels with HCV-796.
Innovations everywhere
The advent of antiviral compounds isn't the only innovation under way for treating HCV. There are also drugmakers, including Flamel Technologies and Human Genome Sciences, attempting to develop improved versions of the interferons. Flamel's drug is in phase 1 testing, and Human Genome Sciences expects phase 3 results from its compound, dubbed albuferon, in 2009.
A more distant future in combating hepatitis C could see the disappearance of the interferons from treatment altogether and the combination use of only antiviral drugs. Roche, Schering-Plough, Abbott, and Gilead Sciences (Nasdaq: GILD) all have the resources to develop antiviral-only combination therapies, similar to what is used to treat HIV. At the AASLD meeting, Schering, Novartis, and Idenix Pharmaceuticals (Nasdaq: IDIX) will present preclinical data on in vitro testing of a polymerase and protease inhibitor in combination treatment without an interferon therapy.
Participants in the upcoming AASLD meeting know that, even though there have been stumbles in 2007 with Idenix's lead HCV drug valopicitabine, Achillion Pharmaceuticals' GS 9132, and ViroPharma's HCV-796, it's still an unprecedented time in the development of HCV therapies.
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Ignorance fuels spread of hepatitis B
http://tvnz.co.nz/
Ignorance is fuelling the spread of hepatitis B in Asia, where patients are failing to get proper treatment and not enough is done to reduce transmission of the virus from mother to child, an expert said.
The 10th leading cause of death worldwide, chronic hepatitis B affects 360 million people globally.
Of these, 281 million are in Asia, and one out of every four of them will die from either cirrhosis - scarring of the liver - or liver cancer later in life.
Symptoms such as jaundice, fatigue, abdominal pain, loss of appetite, nausea and joint pain may not surface in 30% of cases, and they are even less common in children.
As such, many people usually do not know they are infected until it is too late, and those who do have little impetus to get treated or have regular check-ups, according to the results of a survey carried out in 10 places in Asia this year.
"Ignorance helps the transmission of the disease and the survey finds this ignorance results in people giving up on the chance of proper treatment...they don't think it's important to be treated because they don't have symptoms," said Nancy Leung, an expert on the disease and associate professor at the Chinese University's department of medicine and therapeutics.
The survey covered 1,500 people diagnosed with chronic hepatitis B in China, Hong Kong, South Korea, Malaysia, the Philippines, Indonesia, Singapore, Taiwan, Thailand and Vietnam and who were taking anti-viral drugs to suppress the virus.
Although 77% of them said they knew an average or a great deal about the disease, substantial numbers of them (36% and 27%, respectively) were unaware that the main routes of transmission were from mother-to-child and through sex.
Overwhelming numbers mistook hepatitis B for hepatitis A, with 73% in China, 70% in the Philippines and 63% in Singapore thinking that eating infected food was the major cause.
Thirty-eight percent did not know how they came to be infected.
In China and the Philippines, 53% and 46% thought they caught the virus from food.
In Indonesia and Vietnam, 57% and 44% cited poor health as the cause.
Highlighting the seriousness of the disease, Leung said 10% of Hong Kong's seven million strong population, or 700,000 people, suffer from chronic hepatitis B.
And despite the city's advanced health care system, only a fraction of patients are getting adequate care.
"In Hong Kong, less than 10% of patients with chronic hepatitis B are being treated, only 20% are being properly monitored and assessed," Leung said.
Almost all chronic hepatitis B sufferers were infected before they were born or when they were very young.
In Hong Kong, 60% of sufferers are believed to have been infected by their mothers, while 40% were infected when they were very young, usually through blood contact with infected playmates via open sores and small breaks in the skin.
"Infections in adulthood would in all likelihood not be chronic, they would be cured," said Leung, referring to the intense immune response such an infection would trigger in an adult, who would be able to get rid of the virus completely.
Conversely, in an infant or a very young child, they are very often unable to flush out the virus, and it remains in their livers, multiplying and then creating havoc over time.
Pregnant mothers who are carriers of the disease must inform their doctors and infants can be effectively protected if they are given a vaccine and hepatitis B immune globulin within 12 hours after birth.
A second dose is given 1-2 months later and a third dose at age six months.
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New Hepatitis C Antiviral CB5300 Identified by Canopus BioPharma Researchers to Enter Clinical Trial Assessment
http://biz.yahoo.com
LOS ANGELES--(BUSINESS WIRE)--Canopus BioPharma, Inc. (OTCPK: CBIA), a biotechnology company developing pharmaceutical products and assay methods for patients suffering from infectious disease, radiation sickness, cancer, and addiction, announced today that CB5300, its new antiviral drug candidate for treatment of Hepatitis C, will be entering into clinical trial assessment following successful in-vitro screening. The screening process was completed in September 2007 at a major contract research institute in Maryland, which resulted in a research report concluding that a family of molecules has been identified as potent inhibitors of flaviviruses.
Researchers performed the in-vitro examination of bovine viral diarrhea (BVDV), which is a flavivirus in the same family as human Hepatitis C virus (HCV). This approach was taken because HCV can’t be grown in human tissue culture. Instead, BVDV is used as a model virus to determine if experimental compounds are efficacious in inhibiting viral growth.
Canopus BioPharma’s in-vitro research report concludes: “In our experience no drug in this in-vitro system has been recorded to completely inhibit BVDV or act in any way superior to the compounds submitted by Canopus BioPharma. BVDV is a particularly aggressive virus, the most accurate model for Hepatitis C available.”
CB5300 molecules have been previously approved for human use and used in the food industry since 1813, and are generally regarded as safe (GRAS) by the United Stated Food and Drug Administration (FDA) and other international food and drug regulatory bodies. Canopus BioPharma has patents pending incorporating these molecules as antivirals. Clinical trial centers specializing in HCV treatments in the United States and Australia have agreed to commission Phase II patient studies on behalf of Canopus BioPharma during the next six months.
According to the World Health Organization (WHO), Hepatitis C has been compared to a “viral time bomb.” WHO estimates that about 180 million people, some 3% of the world's population, are infected with HCV, 130 million of whom are chronic HCV carriers at risk of developing liver cirrhosis and/or liver cancer. It is estimated that three to four million persons are newly infected each year, 70% of whom will develop chronic Hepatitis. HCV is responsible for 50%-76% of all liver cancer cases, and two thirds of all liver transplants in the developed world.
About Canopus BioPharma, Inc.:
Canopus BioPharma, Inc. (OTCPK: CBIA) is dedicated to providing the safest, most cost effective and efficacious pharmaceutical products and assay methods to patients suffering from infectious disease, bio-terrorism, cancer, and addiction. With innovative science, proven research and development leadership, and superior products and compounds, Canopus BioPharma has since 2001 been committed to becoming a market trend setter in the new era of healthcare, which is focused on providing affordable therapeutic and diagnostic benefits and pharmaceutical excellence to patients and healthcare professionals worldwide. In addition, the Company is a world leader in the development of novel camelid antibody products to provide unique avenues of progress and improvement in assay methods and monitoring capabilities for physicians, patients and researchers, particularly for food chain protection applications. Canopus maintains staff in Australia, South Africa, Ireland, Panama and the USA. Additional information on the Company is available at www.canopusbiopharma.com.
With the exception of historical information contained in this press release, content herein may contain “forward looking statements” that are made pursuant to the Safe Harbor Provisions of the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and are subject to uncertainty and changes in circumstances. In particular, the Company may not be successful in its efforts commercialize or attain acceptable clinical results for its products. Investors are cautioned that forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from the statements made. These factors include general economic conditions, delays and risks associated with the performance of contracts and research and development programs, uncertainties as a result of research and development, consumer and industry acceptance, litigation and/or court proceedings, regulatory risks including approval of Food and Drug Administration filings, the ability to achieve and maintain revenues and profitability in the Company’s business lines, and other factors discussed in the Company's filings with the Securities and Exchange Commission.
Contact:
Canopus BioPharma
Len Rothstein, 818-980-5008
President
Fax. 818-980-5088
len@canopusbiopharma.com
or
Darrow Associates, Inc.
Jordan Darrow, 631-367-1866
Fax. 631-614-3612
jdarrow@darrowir.com
Source: Canopus BioPharma, Inc.
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Half of UK Students at Risk of Silent Time Bomb Disease
http://www.responsesource.com
Students Admit to Ignorance of Hepatitis C
31st October, London, UK: Results from a survey announced today show that half of British students may be exposing themselves to the deadly hepatitis C virus by engaging in ‘risky’ activities, such as sharing banknotes or straws when snorting drugs, getting a tattoo or piercing and sharing razors and toothbrushes.
The survey, conducted at Fresher’s Weeks around the UK (London, Edinburgh, Brighton, Manchester, Nottingham), also found that two in three admit to ignorance about the hepatitis C virus or they have no idea what the symptoms of hepatitis C are. In comparison seven in ten claim to know quite a lot about sexually transmitted diseases such as HIV, Chlamydia and herpes.
“For parents who have just sent their children off to University this is worrying news,” said Charles Gore, Chief Executive of leading UK charity, The Hepatitis C Trust. “Young people are putting themselves at risk and they seem completely unaware of the dangers associated with their behaviour.”
Hepatitis C virus is a major cause of acute hepatitis and chronic liver disease, including cirrhosis and liver cancer . Approximately 500,000 people in the UK are thought to living with the disease , six times more than those living with HIV . Of these, 90% don’t even know that they are infected with the disease .
The Hepatitis C Trust, which runs the “What Not To Share” campaign, is calling for greater awareness: “We don’t want to tell students not to have fun at university, just be smart about it. Through our campaign, we want to educate young people about the risk factors of hepatitis C and encourage those who may have engaged in risky behaviour in the past to get tested,” Mr Gore commented.
Below are top tips for students starting their university life on “What Not To Share”:
- Use your own toothbrush or razor – and personalise it so no one else can borrow it
- If you get a tattoo or piercing, go to a reputable outlet and make sure the needle is new out of the packet
- And remember, sharing bank notes or straws to snort substances can transmit the hepatitis C virus
About “What Not To Share”
“What Not To Share” is a prevention/awareness campaign drawing attention to the dangers of transmitting this dangerous virus. It has a simple message: Don’t share anything that could come into contact with blood, such as razors, toothbrushes, notes/straws for snorting drugs or any of the paraphernalia involved in intravenous drug injecting. Much of the new infection occurs in people in their 20s and members of the music business have been working closely with The Hepatitis C Trust to make the campaign relevant to this group.
Prevention is better than cure. This is especially true in the case of hepatitis C where ‘cure’ is still only possible in about half of those infected.
For more information on the WNTS campaign please contact Gemma.peppe@hepctrust.org.uk
If you are at all concerned that you may have been exposed to hepatitis C or have symptoms that may be attributed to hepatitis C – please call The Hepatitis C Trust HELPLINE on 0845 223 4424 for more information.
About hepatitis C in the UK
Hepatitis C, one of the most common chronic blood-borne infections, is transmitted primarily through blood or blood products. Hepatitis C can be passed by piercing, tattoos, transfusion, injection, razors, sharing toothbrushes, dental work and by sharing notes. Whether it is coke, speed, ketamine or smack, these powders or something they are cut with, can corrode the inside of the nose and cause a nose-bleed. Sharing notes or straws with someone else’s blood on it carries serious risk. You do not even need to see blood on a note for the virus to be transmitted and it can survive outside the body and remain infectious for some time. Hepatitis C is a highly destructive disease. Day to day symptoms vary from general fatigue, to flu-like feelings through to digestive issues, joint pains, mood swings and depression. Hepatitis C can remain undetected for 20 years without showing symptoms but it can still be causing liver damage.
For more information please contact:
Alex Reid, WeberShandwick
Tel: 0207 067 0184
Email: alreid@webershandwick.com
Holly Brafman, WeberShandwick
Tel: 0207 967 0451
Email: hbrafman@webershandwick.com
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November 1st, 2007
Merck Buys License to Sell New Vaccine for Hepatitis
http://www.nytimes.com/
By ANDREW POLLACK
Merck has licensed the exclusive worldwide rights to sell a new, potentially more powerful vaccine against hepatitis B from Dynavax Technologies Corporation, a biotechnology company that is exploiting new findings about how the immune system works.
Under the terms of the agreement, which is expected to be announced today, Dynavax will receive $31.5 million initially and up to $105 million later, as well as royalties based on sales of the vaccine. Merck will also pay the remaining costs to develop the vaccine.
The vaccine, called Heplisav, is in the final stage of clinical trials and could reach the market by 2010, according to Dynavax, which is based in Berkeley, Calif.
While children are now routinely vaccinated for hepatitis B, many adults have not been. Heplisav is aimed at them.
It requires two injections instead of the three required for the existing vaccines. That means more people are likely to complete their course of vaccination, Dino Dina, the chief executive of Dynavax, said in an interview. Heplisav also appears to provide better protection to older people, who tend to have weaker immune systems.
The Centers for Disease Control and Prevention recommends vaccination for those who might be at risk for the disease, such as people with many sex partners or workers who are exposed to blood, like those in hospitals and clinical laboratories. Hepatitis B can cause liver cancer and cirrhosis.
Merck already sells a hepatitis B vaccine, but Heplisav might provide a new product it can use to compete with GlaxoSmithKline. Mr. Dina said the worldwide market is about $500 million a year.
Heplisav consists of a portion of the hepatitis B virus linked to a short DNA sequence aimed at bolstering immune response. The DNA sequence does that by stimulating a toll-like receptor, one of a family of sentries that activate the immune system’s early response to infection.
Drugs acting through the toll-like receptors have attracted a lot of scientific and pharmaceutical industry attention. But there have been setbacks in development at Dynavax, and at competitors like Coley Pharmaceutical Group and Anadys Pharmaceuticals. So the ultimate usefulness of the technique remains to be seen.
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November 2nd, 2007
Setback in search for hepatitis C treatment
http://www.telegraph.co.uk
By Roger Highfield, Science Editor
The effort to find an effective treatment for the millions of people thought to be infected with the "silent killer" hepatitis C virus has suffered a major setback.
Although rates of infection have declined in the developed world because blood is now screened for this virus, it is estimated that about 0.4 per cent of the population in Britain remains infected with hepatitis C, a virus that is spread by blood and infects the liver.
But most of these 2.5 million people do not know they have the disease, which can remain undetected for up to 20 years without major symptoms of liver disease but can eventually result in hardening of the liver (cirrhosis) and cancer.
Now a discovery by a British team marks a major setback to the urgent quest by drug companies and scientists for effective treatments as the epidemic drives the demand for liver transplantation ever upwards.
"Therapeutic vaccination" to stimulate antibodies to attack the virus had been considered by many to be a promising approach to treat the disease.
The only treatment currently available, a combination of the anti-viral drugs interferon-a and ribavirin, only works in half of cases while the drugs, which need to be taken for six to 12 months, can make patients feel ill and some cannot tolerate them at all.
But study at Birmingham University by a team led by Dr Jane McKeating suggests that scientists looking for an effective treatment for Hepatitis C may face an even bigger task than anticipated. "There is a history of therapeutic antibody treatments for hepatitis c not working and now we know why," she said.
Studies looking into how the virus spreads in liver tumour cells, funded by the Medical Research Council, have demonstrated that the virus seems to use two different routes, which may explain why naturally-occurring antibodies which are present in infected patients are ineffective at controlling the virus.
Thanks to the discovery that some strains of the virus can be grown in the laboratory, developed two years ago by scientists in Japan and America, her team has been able to design experiments to show that the virus does not need to be released by a cell before infecting the next one, but can slip directly from one to the other and avoid the body's neutralising antibodies or medical attempts to boost antibody production.
Although it remains possible that a vaccine could protect an uninfected person from an initial infection, Dr McKeating said that it now looks unlikely that this approach would work as a treatment for someone who has been already infected. "This could have a profound effect on efficacy," she said.
Hepatitis C virus, which was discovered in 1988, affects 170 million people worldwide.
Jennifer Timpe, the lead author of the paper presented their findings at a recent international conference in Glasgow, said: "Viruses can spread by two different mechanisms: via extracellular virus particles or direct cell-to-cell transfer. Until now, HCV was thought to spread by extracellular viruses infecting naïve cells, a route vulnerable to antibodies. But our research shows the virus may use both mechanisms to get around. This is probably why it has been so tricky to tackle."
These latest lab results seem to indicate that the virus' dramatic spread in acute Hepatitis C cases may result from cell-to-cell transfer which appears to be a faster mechanism for the virus to infect new target cells.
Timpe concludes: "Finding that Hep C uses multiple mechanisms for spreading around the body was not great news, but this discovery will allow those of us working in this area to move ahead with a better understanding of the virus. We will have to up our game and find other ways of tackling this relentless virus. Future studies will investigate the pathways of cell-cell transfer of infectivity which may reveal new targets for antiviral therapy."
The late Dame Anita Roddick was a well known sufferer and contracted the illness through an infected blood transfusion in 1971 while she was giving birth to her youngest daughter, Sam.
But she was first diagnosed in 2004 by blood tests. Between 1992 and 2005 a total of 55,000 people in England and Wales were diagnosed with hepatitis C.
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EACS: Studies underline the need for better hepatitis C treatment
www.aidsmap.com
Gus Cairns
A French study presented at the Eleventh European AIDS Conference drew a stark contrast between HIV/hepatitis C (HCV)-coinfected patients for whom hepatitis treatment works and those it doesn’t, and indicates that we should be offering treatment before significant liver damage has occurred – not because of it. And a Spanish study, which found a dismal prognosis for the HIV/HCV-coinfected with decompensated (end-stage) liver disease, reminds us why treatment (and better treatment) is needed.
Stéphanie Dominguez of Pitié Salpetrière Hospital in Paris presented a retrospective review of all patients with documented HIV/HCV coinfection and compared those who received interferon-based therapy with those who never received it.
The group comprised 437 patients, 75% of them men, who first presented to the hospital any time between 1980 and June 2006. The average length of follow-up was nearly ten years.
A reasonable proportion – 230 patients or 52.6% of the total – had received one or more courses of HCV treatment, most of it in recent years and most of it consisting of pegylated interferon plus ribavirin (peg-IFN/RBV).
Thirty-eight per cent of patients achieved the sustained viral response (SVR) which is tantamount to a cure, meaning that they had no detectable HCV in their blood 24 weeks after the end of therapy.
Liver decompensation (see more below) is what happens when the body gives up the struggle to force blood through a damaged liver and true liver failure begins; it is characterised by symptoms such as jaundice, ascites (fluid in the abdomen), varices (enlarged veins in the oesophagus, which can often cause life-threatening bleeds) and sometime encephalopathy caused by liver waste products.
There was a considerably higher risk of decompensation in patients who received HCV treatment than ones who didn’t – but this was because, as is common clinical practice, treatment was mainly offered to more advanced fibrosis, that is in whom significant liver damage had already occurred.
Liver decompensation occurred in 7.2% of the patient group overall, but in 14.3% of those who received treatment compared with 4.4% of those who didn’t.
When treatment worked, however, and an SVR was achieved, the risk of liver disease fell considerably: only 2.3% of patients who achieved an SVR got liver decompensation. The reason the figure wasn’t zero, Dominguez explained, was because in some patients treatment may have worked but the liver damage was already considerable.
The pattern in deaths was the same; 4.6% of the patient group overall died, 8.6% of those who received HCV treatment, but only 1.2% of those who achieved an SVR.
A Spanish study underlined the cost of liver decompensation. Maria López-Diéguez of La Paz University Hospital in Madrid presented findings from a national prospective cohort of 373 HIV/HCV coinfected patients who were already diagnosed with liver cirrhosis and compared those with and without decompensation for mortality and risk factors.
Patients with and without decompensation were similar in terms of age (44 years), gender (20% female), length of HCV infection (23 years) and HIV treatment status (82% on anti-HIV treatment). People with decompensation were much less likely to have received HCV treatment (28% versus 65%) and more likely to have had an AIDS-defining illness (54% versus 33%).
Their mortality was far worse. Nearly half (48.1%) of those with decompensation died during the follow-up period, compared with 6.7% of those without it. Their prognosis was very poor. The percentage either dying, developing liver cancer or having a liver transplant in patients with and without decompensation was 34% versus 5% after a year, 68% versus 8% after two years, and 100% versus 8% after three years. Median time to one of these events was 19 months in people with decompensation and 5.5 years in patients without. Eighteen per cent of patients with decompensation were dead within 18 months of being diagnosed with it.
The one piece of good news was that the incidence of new cases of decompensation was quite low. Four per cent developed it anew within a year, 6% by two years and 7% after three years.
“These results emphasise the critical importance of avoiding the development of end-stage liver disease in HIV/HCV-coinfected patients,” commented López-Diéguez.
Finally, a study of newly-acquired, acute HCV in patients already coinfected with HIV provided more evidence that there is an increasingly epidemic of sexually-transmitted HCV in gay men. Dr Alex Azwa presented data on cases of acute HCV from four European hospitals: the Chelsea and Westminster and Royal Free Hospitals in London, the Pitié-Salpetrière in Paris and the University of Bonn Hospital in Germany.
This was a retrospective analysis of HIV-positive patients presenting with acute hepatitis C between 1999 and 2006. One hundred and fifty patients were diagnosed with acute HCV during this period, two-thirds on the basis of abnormal liver function tests, 11% because they had hepatitis symptoms, and 15% because they’d been in contact with someone else with HCV.
Of these, 131 were gay men, five were injecting drug users and two had both risk factors. Twenty-one per cent showed any sign of hepatitis symptoms.
Two-thirds of patients in Germany and the UK had HCV genotype 1 (HCV-1), but only 20% in France, where most cases were of HCV-4, which seems to have spread from Africa, where it is common.
One unexpected finding was that a much lower percentage of patients cleared HCV spontaneously from their systems than has previously been reported. By the end of 48 weeks only eleven patients (7%) had done so without the aid of treatment. However a number of patients who did receive treatment might have spontaneously cleared their HCV anyway. So the proportion who would have actually done so if peg-IFN/RBV was not available did so lay somewhere between 7% and 28% (eleven spontaneously cleared out of 39 who had not started treatment by 48 weeks).
What was striking was that only 26% of patients who had an undetectable HCV viral load twelve weeks after diagnosis were still undetectable at week 48; it may therefore take as long as a year to find out if someone genuinely has rid their body of HCV. Spontaneous clearance was linked to HCV baseline viral load and CD4 count; the average HCV viral load in those who cleared was 200,000 and in those who did not it was 1.1 million, and the average CD4 count in those who cleared was 623 compared with 426 in those who did not.
The low figures for spontaneous vial clearance, Azwa commented, may be due to re-infections as well as reactivations of HCV.
Finally, Dr Vincent Soriano of Hospital Carlos III in Madrid, giving a general introduction to HCV in Europe, said that there were 15 investigatory antiviral drugs in various stages of development for HCV as well as improved formulations of interferon. Although interferon will probably always be necessary for a complete cure, the treatment picture for HCV should be considerably better in three to four 4 years’ time.
Reference
- Dominguez S et al. Long-term impact of interferon (IFN)-based therapy on lever-related decompensation, hepato-cellular carcinoma (HCC) and liver death in HIV/HCV co-infected patients: a retrospective cohort study. Eleventh European AIDS Conference, Madrid. Abstract PS8/3. 2007.
- López-Diéguez M et al. Morbidity and mortality in HIV infected patients with compensated and decompensated cirrhosis: prospective cohort of 373 patients. Eleventh European AIDS Conference, Madrid. Abstract PS8/4. 2007.
- Azwa A et al. The Natural history of acute hepatitis C (AHC) in HIV co-infected individuals – a European collaborative study. Eleventh European AIDS Conference, Madrid. Abstract PS8/5. 2007.
- Soriano V. New drugs on the horizon for treatment of viral hepatitis. Eleventh European AIDS Conference, Madrid, opening presentation, session PS8. 2007.
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Phase II Study Shows that Nitazoxanide Significantly Improves Response to Standard of Care in Patients with Chronic Hepatitis C
http://www.earthtimes.org
TAMPA, Fla., Nov. 2 /PRNewswire/ -- Romark Laboratories, a privately-owned biotechnology company, today announced results of a randomized phase II clinical trial showing that 79% of interferon-naive patients with chronic hepatitis C genotype 4 receiving nitazoxanide plus the standard of care had a sustained virologic response (SVR), or undetectable level of virus, 12 weeks following treatment, compared to 43% of patients receiving the standard of care without nitazoxanide. The patients treated with nitazoxanide also experienced no relapse and no more side effects than patients who received the standard of care. Interim results from this Phase II clinical trial will be presented on Tuesday November 6 in an oral presentation at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
"Patients treated with nitazoxanide responded earlier and maintained their responses without relapse after receiving only 36 weeks of treatment with peginterferon and ribavirin," said Dr. Emmet B. Keeffe, Chief of Hepatology at Stanford University School of Medicine. "These data suggest the emergence of a new therapeutic approach for treating hepatitis C. While more study is needed to confirm these results in a broader population of patients, nitazoxanide appears to increase the potency of interferon without increasing toxicity or inducing resistance."
Study Details
This Phase II randomized, controlled trial was conducted at two centers in Egypt and is part of the company's STEALTH C (Studies to Evaluate Alinia for Treatment of Hepatitis C) clinical development program, which is designed to evaluate the safety and efficacy of nitazoxanide tablets in combination with peginterferon or peginterferon and ribavirin (standard of care) in patients with chronic hepatitis C.
In the trial, 96 treatment-naive patients with chronic hepatitis C genotype 4 were randomized into three groups to receive either 48 weeks of standard of care treatment (n=40), 12 weeks of nitazoxanide followed by 36 weeks of nitazoxanide plus peginterferon (a dual regimen, n=28), or 12 weeks of nitazoxanide followed by 36 weeks of nitazoxanide plus standard of care treatment (a triple regimen, n=28). An additional 24 interferon-experienced patients were randomized to receive 12 weeks of nitazoxanide followed by either the dual regimen (n=12) or the triple regimen (n=12) for 36 weeks. Patients received 180 microgram injections of pegylated interferon (Pegasys(R)) once per week; nitazoxanide was administered as one 500 mg tablet twice daily; and ribavirin was administered as 1,000 or 1,200 mg daily according to weight.
Results
At 12 weeks following the end of treatment, naive patients who received a triple regimen that included standard of care and nitazoxanide showed a significantly higher SVR (HCV RNA <10 IU/mL, Abbott m2000) than the group receiving the standard of care regimen (79% vs. 43%, respectively) (p=0.006). The data also suggest a potential for eliminating or reducing the role of ribavirin in treating hepatitis C. Patients treated with a dual regimen of nitazoxanide and peginterferon showed an SVR at week 12 following the end of treatment that was not inferior to standard of care (68% vs. 43%, respectively) (+25%; 95% CI: -1%, +47%). Of 24 treatment-experienced patients, the triple regimen (n=12) resulted in an SVR of 25% at week 12 post- treatment, and the dual regimen group (n=12) had an SVR of 8%.
"Results from this trial validate a new approach to treating HCV that focuses on the interaction between the virus and the cell," said Jean-Francois Rossignol, M.D., Director of the Romark Institute for Medical Research. "With confirmation provided by this data we are aggressively pursuing development of nitazoxanide and related drugs to treat chronic hepatitis C and other viral diseases."
Nitazoxanide is the first of a new class of small molecule drugs called thiazolides that inhibit replication of a broad range of viruses. The drug was discovered by Dr. Rossignol and was initially developed by Romark and approved for marketing in the United States as the first treatment of cryptosporidiosis. Serendipitously, the development of nitazoxanide for treating cryptosporidiosis led to the discovery of its antiviral properties and ultimately to the discovery of a promising new class of antiviral drugs.
Romark is currently conducting a U.S. Phase II trial with nitazoxanide plus standard of care in patients with hepatitis C genotype 1 who were previously treated with interferon. The Company also plans to initiate a Phase II trial in treatment naive patients early in 2008.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), a virus spread through direct contact with the blood of infected people. Chronic HCV infection may cause liver cirrhosis or hepatocellular carcinoma. An estimated 3.2 million people in the U.S. are chronically infected by hepatitis C virus. Globally, an estimated 170 million people are chronically infected, with three to four million persons newly infected each year, according to the World Health Organization.
About Romark Laboratories
Romark Laboratories, L.C. (http://www.romark.com/) is a privately-owned biotechnology company committed to the discovery and development of innovative new small molecules for treating infectious diseases, cancers, and autoimmune diseases.
About Alinia
Alinia (nitazoxanide) is indicated in the United States for treatment of diarrhea caused by Cryptosporidium parvum or Giardia lamblia in patients 1 year of age and older. Alinia has not been shown to be superior to placebo for the treatment of diarrhea caused by Cryptosporidium parvum in HIV-infected or immunodeficient patients. The most common adverse events reported by patients receiving Alinia have been abdominal pain, diarrhea, headache and nausea. In controlled trials, the frequency of these events has been similar to patients receiving a placebo. Alinia is an investigational new drug in the United States for treating chronic hepatitis C.
Romark Laboratories
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Pharmasset Presents R7128 14-Day Monotherapy Study Results for the Treatment of Chronic Hepatitis C
http://money.cnn.com
-Nucleoside polymerase inhibitor demonstrates >99% mean decrease in HCV RNA with no serious adverse events-
PRINCETON, N.J., Nov. 2 /PRNewswire-FirstCall/ -- Pharmasset, Inc. announces the results of a 14-day Phase 1 multiple ascending dose monotherapy study of R7128 for the treatment of chronic hepatitis C infection. In this study, being presented as a "late-breaker" abstract at the 58th Annual Meeting of the American Association for the Study of Liver Diseases, R7128 demonstrated potent antiviral activity and was generally safe and well-tolerated. R7128 is an orally administered prodrug of PSI-6130, a cytidine nucleoside analogue polymerase inhibitor of hepatitis C virus (HCV) that is being developed through Pharmasset's collaboration with Roche.
"R7128 has provided positive proof-of-concept that a single, direct-acting antiviral can deliver sufficient potency to suppress HCV in an interferon non- responder population," stated Dr. Michelle Berrey, Pharmasset's Vice President, Clinical Development & Chief Medical Officer. "Since robust synergy has been observed with other potent inhibitors when combined with the standard of care for HCV, we hope that these monotherapy results will translate well when R7128 is used with standard of care for longer duration in a treatment-naive population."
Dr. Rajender Reddy, Professor of Medicine and Surgery in the Division of Gastroenterology at the University of Pennsylvania and a clinical investigator in the study, noted "R7128's safety profile is encouraging, with no serious or treatment-limiting adverse events reported even at the highest dose tested. In addition, there were actually a higher number of adverse events reported in the placebo group than in the treated arms of this study. Safety is an important aspect of new HCV therapies, because the current standard of care is not always as well tolerated as desired."
The R7128 scientific presentation will be available for download in PDF format following the conference in the "R7128 Presentations & Publications" section of Pharmasset's website at http://www.pharmasset.com/pipeline/R7128-publications.asp.
R7128 Phase 1 Multiple Ascending Dose Study Overview
The Phase 1 clinical trial is a multiple center, observer-blinded, randomized and placebo-controlled study was conducted in 40 patients chronically-infected with HCV genotype 1 who previously failed interferon therapy. The primary objective was to assess the safety, tolerability and pharmacokinetics of R7128 after once-daily (QD) or twice-daily (BID) dosing for 14 days. The secondary objective was to assess antiviral activity by measuring the change in HCV RNA.
R7128 Safety Summary
R7128 was gene |
