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October 26, 2006

Announcing a Major Breakthrough in Hepatitis C Treatment

When two separate studies produce identical results, medical innovations quickly follow. Researchers from Scripps Institute and La Jolla Institute for Allergy and Immunology have come to the same conclusion: Altering a specific immune system molecule allows a rat to successfully fight Hepatitis C. If these findings can be reproduced in humans, an entirely new way to eradicate Hepatitis C may be on the horizon.

Major Advance In Fight Against Hepatitis C And Other Chronic Virus Infections

A major finding that could lead to a new approach for treating hepatitis C and other chronic virus infections was announced today by researchers at the La Jolla Institute for Allergy & Immunology (LIAI). The research team, using controlled laboratory studies of mice, was able to eliminate a chronic virus infection in the animals by blocking a key messenger molecule in the immune system. The finding has particular relevance for hepatitis C, a viral illness which can cause liver disease and cancer, but may also be applicable to AIDS, cytomegalovirus and other chronic virus infections.

"This is a significant advance that holds great promise for the treatment of chronic virus infections," said Mitchell Kronenberg, LIAI President & Scientific Director. He noted that the research is particularly exciting because the scientific team was able to completely eradicate the usually chronic infection in the mice, not just tone it down, like many of the current treatment methods for such infections.

The research team, led by Matthias von Herrath, M.D., announced its finding in a paper, "Resolution of a Chronic Viral Infection Following IL-10 Receptor Blockade," published today in the online version of the Journal of Experimental Medicine. A separate study, led by Michael Oldstone from the Scripps Research Institute, produced similar results and was published Sunday in a science journal.

LIAI's research team used a novel method for tackling a chronic viral infection, which involved releasing the disease-fighting power of the immune system by blocking the interleukin-10 (IL-10) messenger molecule receptor with a simple antibody. Normally, this molecule, which is produced at substantial levels during hepatitis C, HIV and cytomegalovirus infections, acts to suppress the immune system's attack on chronic virus infections. "We thought, 'what if we try to correct what the immune system seems to be doing wrong in response to many chronic viral infections?,'" said von Herrath. "So we unleashed the power of the immune system by using an antibody to block the IL-10 receptor. This taught the immune system to take the right action and fight the disease."

The discovery by scientific researchers that mice chronically infected with lymphocytic choriomeningitis virus produce large amounts of IL-10 led to the development of this new intervention. Von Herrath used a version of the virus that causes chronic infections in a study involving 40 infected mice. The mice were treated with the IL-10-blocking antibody for two weeks. "They got better after one week," he said. "After two weeks, the infection was resolved in the majority of the mice and, in the end, all animals were able to cope with the virus. They developed a normal antiviral immune response, gained weight and returned to a healthy state." Von Herrath noted that their studies showed that the treatment worked best when given immediately after infection. "The later you give it after the infection, the lesser the efficacy," he said.

Von Herrath said that future studies in humans should primarily target hepatitis C because it causes the body to produce the most IL-10 of any of the chronic virus infections. Hepatitis C has been compared to a "viral time bomb." The World Health Organization estimates that about 180 million people, some 3% of the world's population, are infected with hepatitis C virus, 130 million of whom are chronic carriers at risk of developing liver cirrhosis and/or liver cancer. The hepatitis C virus is responsible for 50-76% of all liver cancer cases, and two thirds of all liver transplants in the developed world. Current estimates in the U.S. are that 3.9 million Americans are chronically infected with hepatitis C.

Currently, hepatitis C is treated with a variety of drugs, with only modest success. "The problem is you need to strengthen the immune system to fight the (chronic) virus, but in doing so it may destroy too many cells. This cellular damage can eventually become intolerable for the body," Von Herrath explained, a condition known as immunopathology. However, in their studies with IL-10, "we found that by blocking this molecule, you can release the brakes on the immune system at a crucial juncture," he said. "This results in an immune system attack that is intense enough to rid the body of the disease, but not so high as to cause immunopathology."

Von Herrath said the research team will continue to expand on the finding. "One of the next steps will be to test the IL-10 blocking antibody on human cells in the lab to see whether these cells also become normal and functional against the virus and to test combination therapies that add viral vaccines, anti-viral drugs and other antibodies to the IL-10 receptor blockade. Combination therapies bear the promise to minimize potential side effects while achieving synergy in combating the viral disease."

Source: Medical News Today

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October 25, 2006

Dangerous Lack of HCV Awareness in College Students

American college students are not sufficiently educated about Hepatitis C, according to a recent study. A startling percentage of surveyed students are at risk for contracting the virus due to some fairly common college activities. If you have a loved one who is an undergraduate student, you will want to send them this link to discover the risk factors for their own protection.

75 Percent of College Students Report Risk Factors for Hepatitis C

College undergraduates in the United States do not recognize the magnitude of their risk behaviors for contracting Hepatitis C, according to a survey conducted at a large Midwestern university. Researchers found that 75 percent of undergraduates in this study had a potential hepatitis C risk factor, from tattoos to sharing body jewelry. Results of this study were presented at the 71st annual Scientific Meeting of the AmericanCollege of Gastroenterology in Las Vegas.

Researchers surveyed 610 college undergraduates on their knowledge of hepatitis C and their personal experience with traditional (intravenous drug use, blood transfusions) and novel risk factors (sharing of body jewelry, tattoos). Twenty-seven percent didn’t know hepatitis C virus (HCV) could be spread through intravenous drug use, while 77 percent of students were unaware HCV could be transmitted by intranasal cocaine use. Furthermore, 53 percent of students reported sharing pierced jewelry.

“We were surprised by the proportion of undergraduates who were inadvertently putting themselves at risk for hepatitis C,” says Thomas Shehab, MD, of St. Joseph Mercy Health System and Huron Gastro. “In addition to well documented traditional risk factors, we are concerned about students who may be putting themselves at risk for this serious disease with even something as simple as sharing pierced body jewelry.“

One of the other concerning findings was the low frequency that the undergraduates were asked about viral hepatitis/HIV risk factors when seen by their primary-care providers. “The majority of the group had been to the physician for a healthcare maintenance examination in the last three years, but during that visit most had never been asked about behaviors that put them at risk for serious infection,” says Shehab. Given the prevalence of these behaviors, researchers say further study should focus on this high-risk age group.

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The infection is spread by blood-to-blood contact with an infected person. HCV can be spread through contaminated needles, unsterilized tattoo or body piercing equipment, and shared toothbrushes, razors, nail clippers or other hygiene items that have HCV-infected blood on them. There is no vaccine against HCV. Serious complications include chronic liver disease, cirrhosis, and liver cancer.

Source: American College of Gastroenterology

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October 24, 2006

Promising Partnership in Treating Hepatitis C

Two leading companies are merging in an effort to accelerate Hepatitis C treatments. The goal of this collaboration is to further the development of Hepatitis C protease inhibitors.

Roche and InterMune to develop hepatitis C products

Pharmaceutical Business Review Online
By Victoria Harrison

Roche and InterMune have signed an agreement to develop and commercialize candidates from InterMune's hepatitis C protease inhibitor program

The agreement includes InterMune's lead compound ITMN-191, which is expected to enter clinical trials before the end of the year. The companies will also collaborate on a research program of novel second-generation hepatitis C protease inhibitors.

"We believe this partnership will help accelerate the development of ITMN-191 and future second-generation protease inhibitors," said Dan Welch, CEO of InterMune.

Roche will exclusively license ITMN-191 and will have the right to exclusively license further hepatitis C protease inhibitor development candidates resulting from the research collaboration.

InterMune will conduct phase I studies of ITMN-191, and thereafter Roche will lead clinical development and commercialization. Upon closing, InterMune will receive from Roche an upfront payment of $60 million. InterMune could potentially receive up to $470 million in milestones as a result of the deal. The companies will co-commercialize the product in the US.

The economic terms for ITMN-191 could also apply to additional compounds that InterMune and Roche develop.

The transaction will close following the expiration or early termination of an antitrust regulatory waiting period.

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October 20, 2006

New HCV Combination Therapy Means Fewer Sick Days

Currently in a Phase 2b clinical trial to evaluate its efficacy, safety and quality of life effects, HCV participants on Albuferon^TM with Ribavirin are showing positive results. Compared to one of the most popular treatment options available, interim trial results after 12 weeks show more favorable life markers with this new drug combination.

Source: Human Genome Sciences, Inc

Positive Interim Quality-of-Life Data From Phase 2B Trial of Albuferon(TM) With Ribavirin in Treatment-Naive Hepatitis C Patients

Albuferon associated with fewer missed work days and better patient-reported quality-of-life scores than pegylated interferon through week 12 -

ROCKVILLE, MD -- October 16, 2006 -- Human Genome Sciences, Inc. today reported 12-week interim quality-of-life results from a phase 2b clinical trial to evaluate the efficacy, safety and impact on health-related quality of life of Albuferon(TM) in combination with ribavirin in patients with genotype 1 chronic hepatitis C (HCV) who are naive to interferon alpha-based treatment regimens.

The interim results demonstrate that all Albuferon treatment groups consistently performed favorably through week 12 compared to the pegylated interferon alpha treatment group, based on patient-reported disability days and health-related quality of life as measured by the SF-36 health survey. The data were presented over this past weekend at the annual Australian Gastroenterology Week in Adelaide.

Health-related quality-of-life issues, including lost days of work and normal activity, pose a significant challenge for patients undergoing treatment for chronic hepatitis C," said Stephen Pianko, MD, FRACP, PhD, Associate Professor of Medicine, Monash University (Melbourne, Australia). "Interim results of the current study suggest that Albuferon may have the potential to offer a therapeutic alternative with less impairment of health-related quality of life, and fewer disability days, compared with the current standard of care, with at least comparable safety and efficacy. We look forward to continuing the evaluation of Albuferon to determine its appropriate role in the treatment of hepatitis C."

"Through week 12 of the phase 2b study, patients in the Albuferon treatment groups recorded fewer missed work days and, based on the SF-36 health assessment, reported better quality of life than patients in the pegylated interferon treatment group," said David C. Stump, MD, Executive Vice President, Drug Development, HGS. "This result was observed in both the physical and mental component summary measures, as well as in the 8 individual domain scores. The SF-36 results in mental health suggest significantly less impairment of psychological well-being across the Albuferon treatment groups."

About the Albuferon Phase 2B 12-Week Quality-of-Life Results
Albuferon treatment groups recorded fewer disability days and reported less impairment of health-related quality of life through week 12 of the phase 2b study than patients in the pegylated interferon treatment group. The 900- mcg Albuferon dose administered at 2-week intervals was associated with 75% fewer disability days, and the 1200-mcg Albuferon doses administered at 2-week and 4-week intervals were associated with 25% fewer disability days.

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October 19, 2006

HCV Genotype 1: Anti-viral HCV Drug Advances to Phase II

Granted fast track status, Roche's® R1626 is beginning a Phase II study to evaluate its safety and HCV anti-viral activity. Administered in combination with PEGASYS® and COPEGUS®, this trial is now enrolling people with HCV genotype 1 who have previously not received treatment.

BASEL, Switzerland, October 13
FDA Grants Fast Track Status to R1626
excerpt taken from Earthtimes.org

Roche announced today the start of the first phase II development studyto evaluate R1626, their promising new polymerase inhibitor, for the treatment of hepatitis C. The investigational drug has also been granted FastTrack status by the US Food and Drug Administration (FDA), a program designed to facilitate the development and to expedite the review of new drugs withthe potential to help treat serious or life-threatening conditions.

R1626 has been shown in an earlier study to have a strong antiviraleffect against the hepatitis C virus. In the phase I study[1] , the drug achieved significant reductions in viral load in chronic hepatitis C patients infected with the difficult-to-cure genotype 1 virus. By moving R1626 intophase II trials, Roche signifies its commitment to finding more therapeutic solutions for patients with hepatitis C. This trial will evaluate the safety and antiviral effects of R1626 in combination with the current standard of care for hepatitis C, Roche's PEGASYS (peginterferon alfa-2a (40KD)) and COPEGUS (ribavirin).

About the phase II trial

This on-going multicenter phase II trial that is enrolling patients with genotype 1 chronic hepatitis C who have not previously received treatment.

Patients are randomised into four treatment groups. These treatment groups are:

- Group A: R1626 1500mg twice a day + Pegasys 180mcg as a subcutaneous injection every week for 4 weeks

- Group B: R1626 3000mg twice a day + Pegasys 180mcg as a subcutaneous injection every week for 4 weeks

- Group C: R1626 1500mg twice a day + Pegasys 180mcg as a subcutaneous injection every week + Copegus 1000-1200mg daily for 4 weeks

- Group D: Pegasys 180mcg as a subcutaneous injection every week + Copegus 1000-1200mg daily (standard of care group) for 4 weeks

Following the first 4 weeks of treatment, all patients will receive Pegasys 180mcg subcutaneously every week + Copegus 1000-1200mg daily for another 44 weeks, making the total treatment duration of 48 weeks. The objectives of the study are to evaluate the 4 week safety and antiviral effect of combining R1626 with Pegasys alone or R1626 with Pegasys plus Copegus.

The study is currently enrolling patients in the US. Patients and healthcare providers interested in the trial can find more information at www.roche-trials.com.

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October 06, 2006

New Hepatitis C Drug Enters Phase III Trial

Nearly 1,300 people with Hepatitis C genotype 1, the most common strain in the US, will be testing a new drug in a Phase III trial. The new drug, Albuferon, will be compared with the current gold standards of HCV treatment, PEGASYS® and PEG-IFN alpha 2a.

Human Genome Sciences tests Hep C drug
United Press International

ROCKVILLE, Md., Oct. 4 (UPI) -- U.S. firm Human Genome Sciences said Wednesday it has begun a phase 3 trial of Albuferon in patients with chronic hepatitis C.

The company said it would test its albumin-interferon alpha 2b in more than 2,000 treatment-naive patients with the disease.

"We believe that Albuferon could become the best-in-class immunomodulator in treatment regimens for chronic hepatitis C, and we are pleased to move this important program forward," said H. Thomas Watkins, HGS's president and chief executive officer. "Advancing Albuferon to Phase 3 development is a major step toward the transformation of HGS into a development and commercialization company."

The phase 3 development program will compare therapy with Albuferon in combination with ribavirin, versus PEGASYS, or PEG-IFN alpha 2a, in combination with ribavirin.

The testing will consist of two separate clinical trials -- ACHIEVE 1, which will enroll at least 1,278 patients with chronic hepatitis C genotype 1 -- and ACHIEVE 2/3, which will involve a minimum of 918 subjects with chronic hepatitis C genotype 2 or 3.

The studies will assess the drug's efficacy, safety and impact on health-related quality of life.

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October 05, 2006

Latest Test May Predict Hepatitis C Treatment Results

When undergoing interferon/ribavirin treatment for Hepatitis C, being able to judge the treatment's chance of success is critical in deciding whether to continue. By increasing an RNA test's sensitivity, American researchers have found a more reliable method for physicians to judge treatment outcome.

Abstract from Hepatology August 2006
Volume 44, Issue 2, Pages 360-367

HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial

For making treatment decisions related to chronic hepatitis C, the utility of HCV RNA tests with increased sensitivity has not been defined. Prior interferon nonresponders with advanced fibrosis (n = 1,145) were retreated with peginterferon alpha-2a and ribavirin.

Patients who were HCV RNA-negative by a polymerase chain reaction (PCR)-based assay (Roche COBAS AmplicorTM HCV Test, v. 2.0; lower limit of detection [LOD] 100 IU/mL) at week 20 (W20) received treatment for 48 weeks.

Stored specimens were tested using the Bayer VERSANT HCV RNA Qualitative (TMA) Assay (LOD 9.6 IU/mL) and compared to PCR results for the ability to predict sustained virological response (SVR; defined as undetectable HCV RNA by PCR at W72).

Nearly all PCR-positive samples (1006/1007, 99.9%) were positive as assessed by TMA. Among 1,294 PCR-negative samples, 22% were TMA-positive.

Negative TMA results were more predictive of SVR than were negative PCR results at W12 (82% vs. 64%, P < .001) and at W20 (66% vs. 52%, P = 0.001).

SVR was more likely the earlier TMA had become negative during treatment (82% at W12, 44% at W20, 20% at W24).

Among 45 patients who were TMA-positive but were PCR-negative at W20 and W24, none achieved SVR (95% CI: 0%-8%).

Approximately 10% of patients with a single positive TMA result at the end of treatment still achieved SVR.

In conclusion, negative TMA results at or after W12 were superior to negative PCR results for predicting SVR. In patients with negative PCR results during treatment, a single positive TMA test did not exclude SVR, although persistently positive tests did.

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October 04, 2006

New HCV Combination Therapy

The current medications composing HCV combination therapy are being challenged by Valeant Pharmaceuticals. A recent study reported that HCV therapy with interferon and Viramidine® has fewer side effects than today's standard combination therapy.

Valeant Pharmaceuticals Reports VISER2 Results for Viramidine®
Company Initiates Phase 2b Weight-Based Dose-Ranging Study

COSTA MESA, Calif., September 12, 2006 – Valeant Pharmaceuticals International (NYSE: VRX) today reported summary results of VISER2, the second of two Phase 3 pivotal trials, for Viramidine®. The company is developing Viramidine (taribavirin hydrochloride), a nucleoside (guanosine) analog prodrug of ribavirin, in oral form, for administration in combination with a pegylated interferon for the treatment of chronic hepatitis C in treatment-naïve patients. The VISER2 trial included two co-primary endpoints: one for safety (superiority to ribavirin in the incidence of anemia) and one for efficacy (non-inferiority to ribavirin in sustained viral response, SVR).

The VISER2 study did not meet the non-inferiority efficacy endpoint on an intent-to-treat (ITT) basis, with overall SVR rates of 40 percent versus 55 percent for the Viramidine and ribavirin arms, respectively. However, consistent with the results seen in VISER1, SVR rates in VISER2 trended higher among patients receiving increased exposure on a mg/kg basis in the Viramidine arm without a substantial increase in the anemia rate.

Consistent with results from the VISER1 trial released earlier in the year, VISER2 confirmed the safety advantages of Viramidine. Anemia rates (Hgb < 10g/dL) during the treatment period were significantly lower in patients treated with Viramidine than those treated with ribavirin (6 percent versus 22 percent; p<0.001).

As a result of the combined VISER1 and VISER2 data, the company also announced that it is initiating a Phase 2b program to evaluate the efficacy of Viramidine at higher doses. The Phase 2b program is a multi-center, randomized, parallel, open-label study in 240 treatment naïve, genotype-one patients and will evaluate Viramidine at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alpha-2b. There also will be a control group comprised of ribavirin and pegylated interferon alpha-2b. Treatment duration will be 48 weeks with a post-treatment follow-up period of 24 weeks. Based on a 12-week interim analysis of this study, the company will decide whether to begin a third Phase 3 study at the appropriate higher dose indicated by the Phase 2b study. The company will seek to co-develop the product should it decide to pursue another phase 3 registration trial next year.

Timothy C. Tyson, president and chief executive officer, said, “As expected, VISER2 results were consistent with those seen in VISER1. Although VISER1 and 2 did not meet non-inferiority efficacy endpoints, Viramidine demonstrates meaningful clinical efficacy. Our retrospective analyses of 750 patient plasma samples indicate that Viramidine could be as effective as ribavirin at higher doses. These analyses, coupled with feedback from the medical community that there will continue to be a strong need for ribavirin or ribavirin analogues in the treatment of hepatitis C, indicate that further clinical testing is prudent. Our Phase 2b program should provide us with sufficient information at little relative cost and time to confirm the dose response, select an appropriate dose, test safety at higher doses, establish the path for registration of the drug and make a go/ no-go decision .”

The company also announced the issuance of a U.S. patent for Viramidine for use in the treatment of hepatitis C, which will not expire until 2020.

The majority of adverse events other than anemia and gastrointestinal side effects were similar between treatment groups. The anemia rate was lower in the Viramidine arm, while the gastrointestinal rate was lower in the ribavirin arm. The most common other adverse events associated with combination therapy included fatigue, headache, insomnia, depression and myalgia.

VISER2 Trial Design

The VISER2 trial (VISER stands for VIramidine’s Safety and Efficacy vs. Ribavirin) evaluated a fixed 600 mg BID dose of Viramidine to a weight-based 1,000/1,200 mg daily dose of ribavirin, both in combination with peginterferon alfa 2a. The study, conducted in the United States, Canada, Europe, Israel, Argentina and Australia , enrolled 962 treatment-naïve subjects with chronic HCV. Treatment duration was based on genotype, with genotypes 2 and 3 receiving 24 weeks of treatment and genotype non 2, 3 receiving 48 weeks of treatment, each with a post-treatment follow-up period of 24 weeks. The study was stratified for genotype, weight and viral load.

Additional information regarding the Phase 3 trial will be furnished by the company today with the Securities and Exchange Commission on Form 8-K and is also available on the company’s Web site at www.valeant.com.

Viramidine is an investigational compound that has not been found by the Food and Drug Administration (FDA) or any other regulatory agency to be safe or effective in the diagnosis, mitigation, treatment or cure of any disease or illness. It may not be sold or promoted in the United States unless and until FDA has approved a New Drug Application. Similar restrictions apply in other countries.

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