November 16, 2010

New Indication Okayed for Chronic Hepatitis B Drug


From the November 2010 Issue of Renal And Urology News

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Public release date: 16-Nov-2010
Contact: Kathleen Harrison
HarrisoK@mskcc.org
646-227-3956
JAMA and Archives Journals

Treatment of inoperable advanced liver cancer with the agent doxorubicin (routinely used to treat this condition) in addition to the agent sorafenib resulted in greater overall survival and progression-free survival, compared to patients who received treatment with doxorubicin alone, according to a study in the November 17 issue of JAMA.

"Hepatocellular [liver] carcinoma (HCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases per year. Patients with inoperable or metastatic disease have a median [midpoint] survival of only a few months. Despite the lack of a clear survival benefit, doxorubicin has become a routinely and widely used agent in the treatment of HCC," according to background information in the article. Sorafenib has shown a statistically significant increase in median overall survival compared to placebo. A phase 1 study assessing the feasibility and tolerability of sorafenib in combination with doxorubicin for patients with solid tumors has shown promise. The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial.

Ghassan K. Abou-Alfa, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted a randomized, phase 2 study of doxorubicin plus sorafenib and doxorubicin plus placebo in patients with advanced HCC. The study, conducted from April 2005 to October 2006, included 96 patients (76 percent male; median age, 65 years) who were randomly assigned to receive doxorubicin intravenously every 21 days plus either sorafenib or placebo orally twice a day. The date of the last patient's follow-up was April 2008.

Following complete accrual, an unplanned early analysis for efficacy was performed by the independent data monitoring committee, so the trial was halted. The 2 patients remaining in the placebo group at that time were offered sorafenib.

There were 51 total time-to-disease progression events (24, doxorubicin plus sorafenib vs. 27, doxorubicin plus placebo). Time to disease progression was a median of 6.4 months for patients who received doxorubicin plus sorafenib and 2.8 months for those who received doxorubicin plus placebo.

Sixty-three patients died during the course of the study: 25 in the doxorubicin-sorafenib group; 38 in the doxorubicin-placebo group. Median overall survival was 13.7 months among patients treated with doxorubicin plus sorafenib vs. 6.5 months among those who received doxorubicin plus placebo. Analysis indicated a 51 percent reduction in the risk of death in patients treated with doxorubicin and sorafenib vs. doxorubicin and placebo.

The number of total progression-free survival events was 70, including 32 in the doxorubicin-sorafenib group and 38 in the doxorubicin-placebo group, with the median progression-free survival being 6 months among patients treated with doxorubicin plus sorafenib vs. 2.7 months among those who received doxorubicin plus placebo. Analysis showed a 46 percent reduction in the risk of progression or death among patients treated with doxorubicin plus sorafenib vs. doxorubicin plus placebo.

Toxicity profiles were similar to those for the single agents.

"In summary, among patients with advanced HCC, treatment with sorafenib doxorubicin compared with doxorubicin plus placebo resulted in greater median time to progression, overall survival, and progression-free survival. The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined. This trial has served as the basis for the ongoing phase 3 trial of sorafenib plus doxorubicin vs. sorafenib alone," the authors conclude.

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(JAMA. 2010;304[19]:2154-2160. Available pre-embargo to the media at http://www.jamamedia.org/)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Rapid Hepatitis C Antibody Tests Show Wide Range of Results

Bob Roehr

November 16, 2010 (Denver, Colorado) — The first generation of rapid screening tests for the hepatitis C virus (HCV) antibody, which use blood and oral fluids, underwent field testing in September at 4 sites: Dallas, Texas; Denver, Colorado; Seattle, Washington; and New York City. The tests had considerable variation in performance across the 4 test sites, with wide ranges in sensitivity, specificity, positive predictive value, and negative predictive value.

Bryce Smith, PhD, from the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the project's team leader, presented the initial findings from 5 rapid test kits here at the American Public Health Association 138th Annual Meeting.

Three diagnostic manufacturers submitted 5 different test kits that used oral fluid, blood obtained from a finger stick, or both. The rapid HCV assays evaluated were the Dual Path Platform HCV rapid assay (Chembio); the Multiplo Rapid HIV/HCV Antibody Test (MedMira Laboratories); and the Hepatitis C Rapid HCV Antibody Test (OraSure Technologies).

The comparators were the currently approved standard assays: Abbott AxSYM anti-HCV microparticle immunoassay (Abbott), used in New York City and Seattle; ADVIA Centaur HCV Chemiluminescent Immunoassay (Bayer), used in Dallas; and HCV Version 3.0 ELISA Test (Ortho), used in Denver.

The confirmatory test for all was the Recombinant Immunoblot Assay HCV 3.0 SIA (Chiron).

"There was considerable variation in performance characteristics across sites and across rapid tests, with substantial ranges in sensitivity, Dr. Smith and colleagues report. Sensitivity ranged from 78.9% to 97.4%, and specificity ranged from 80.0% to 100%.

Dr. Smith said the sensitivity appears to be greater for blood than for oral fluid, but this round of evaluations was not powered to assess that difference.

"There was only 1 variable that predicted false results, and that was [coinfection with] HIV" — that occurred only with the oral test at the New York City site.

"We cannot compare these across cities at all," he said. "They all used different immunoassays, they were all different testers, they all had different participants, and they were all using different commercial labs with uniquely different protocols. But it does give us a sense of what the sensitivity and the specificity look like when we use these in the field."

"The most sensitive [kits] certainly are appropriate as a screening test for high-risk [people, such as those] who inject drugs," Dr. Smith noted. He envisions using them at syringe exchange and methadone treatment sites, health fairs, in military field operations, and elsewhere. He also believes they will be a more cost-effective alternative at low-volume sites.

Dr. Smith said they plan to start prospective studies of the rapid tests in March or April 2011, and should have preliminary data within the year. Already, the CDC "is talking within the division about how rapid testing can be integrated into our HCV testing algorithm." But that probably will not be finalized and publicly available until after the first test is on the market.

The OraSure rapid test has already been approved by the US Food and Drug Administration (FDA) for laboratory use with venous blood; the finger stick application is under FDA review. The company is conducting studies toward a CLIA (Clinical Laboratory Improvement Amendments) waiver, which would allow for nonlaboratory use of the screening test in the field by minimally trained staff.

Stephen R. Lee, PhD, OraSure's chief science officer, told Medscape Medical News that they have not yet submitted data on the oral swab version of the HCV screening test.

In a separate conversation with Medscape Medical News, Dr. Smith acknowledged that the case for rapid testing for HCV is not as strong as it is for HIV or other infections where there is significant forward transmission through sexual activity. He believes it will be most useful in situations like methadone maintenance programs, where there is "a case management element" to get people into care if they test positive for HCV.

He said 3 different groups are working on "an antibody/antigen test. Then you wouldn't just know that somebody was exposed, you would know that somebody was chronically infected." That will make a real difference in clinical practice, Dr. Smith explained, because with an antibody test alone, physicians "are not always inclined to follow up. But if somebody is chronically infected, they have to look at it harder."

Dr. Smith emphasized the importance of linking testing to care. This will be an important part of the CDC algorithm when it is released.

"You shouldn't be doing rapid testing if you cannot make sure that you can at least connect individuals with a medical evaluation of some sort, preferably that will involve a [polymerase chain reaction test], so that they can be assessed for chronic infection, and if they are, be referred for care," he said.

The CDC funded the studies in collaboration with local departments of health; the companies contributed test kits for evaluation. Dr. Smith has disclosed no relevant financial relationships. Dr. Lee is an employee of OraSure.

American Public Health Association (APHA) 138th Annual Meeting: Abstract 4024.0. Presented November 9, 2010.

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The Standard of Care Will Change Significantly With the Introduction of New Classes of HCV-Specific Antiviral Agents, According to Findings from Decision Resources

BURLINGTON, Mass., Nov. 16, 2010 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, owing to the launch of several novel agents, the hepatitis C virus (HCV) drug market will more than triple from approximately $2 billion in 2009 to nearly $7.5 billion in 2014 in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan. Thereafter, the market will substantially decrease to $4.6 billion in 2019 due to decreasing prevalence of the disease and the high efficacy of new treatment regimens.

The Pharmacor 2010 findings from the topic entitled Hepatitis C Virus reveal that the standard of care for the indication will change significantly with the introduction of new classes of HCV-specific antiviral agents, such as protease inhibitors and polymerase inhibitors. Compounds from these new classes will initially be added to the backbone of currently used agents, forming triple or quadruple treatment regimens that are expected to be more efficacious than the current standard of care -- peg-IFN/ribavirin.

"Although complete elimination of peg-IFNs and ribavirin agents is highly desirable owing to their side effects, this change is unlikely to occur over the next decade," said Decision Resources Analyst Alexandra Makarova, M.D., Ph.D. "However, decreased treatment durations resulting from the addition of new antivirals could increase the tolerability of treatment regimens. The launch of novel HCV-specific agents will increase the size of the drug-treated population, owing mainly to re-treatment of prior non-responders as well as increased referral and drug-treatment rates."

The current standard of care for HCV -- often a nearly year-long treatment -- cures only about half of patients and is associated with severe side effects. Although the incidence of HCV has declined dramatically after the introduction of prevention measures such as blood donor screening in the early 1990s, prevalence is still high due to the large cohort of aging HCV-infected patients, many of whom have failed prior treatment and are waiting for new therapeutic options.

The findings also reveal that, owing to the large commercial potential which is well-recognized by drug developers, the HCV pipeline remains highly competitive. Agents in late-stage development -- namely Vertex/Johnson & Johnson/Mitsubishi Tanabe Pharma's telaprevir, Merck's boceprevir, Johnson & Johnson/Medivir's TMC-435, Roche/Pharmasset's RG-7128 and Pfizer's filibuvir -- are each expected to drive HCV market growth through 2019. Over the next several years, HCV treatment is expected to consist of cocktails of therapies that target HCV with different mechanisms of action.

About Pharmacor 2010

The newly redesigned Pharmacor advisory service offers clients in the biopharmaceutical industry the most up-to-date information available on commercially significant disease topics.

About Decision Resources

Decision Resources (http://www.decisionresources.com/) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.

About Decision Resources, Inc.

Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources, Inc. at http://www.decisionresourcesinc.com/.

For more information, contact:

Decision Resources, Inc.
Christopher Comfort
781-993-2597
ccomfort@dresources.com

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Hepatitis C: Top 10 Treatment Centers

Tuesday, 16 Nov 2010 12:00 PM

Hepatitis C is a viral liver disease that may include pain in the liver or abdominal area, and jaundice like symptoms where both the white of the eyes and the skin turn yellow. Hepatitis may cause the urine to appear dark in color while stools appear pale. The disease is also marked by fatigue, confusion, and irritability.

Other symptoms during the onset of the infection include a loss of appetite, diarrhea, nausea, and vomiting. Some chronic Hepatitis C cases have symptoms of sleep disturbance, itchy skin, vomiting blood, hallucination, edema or fluid retention, and swelling of the abdomen, legs, and face.

The top ten treatment centers for Hepatitis C are:

1. Gastroenterology Associates of East Bay Medical Group, Berkeley, California

2. Atlanta Gastroenterology Associates, Atlanta, Georgia

3. Idaho Gastroenterology Associates, Meridian, Idaho

4. Johns Hopkins University, Baltimore, Maryland

5. Carolinas Center for Liver Diseases, Charlotte, North Carolina
 
6. Baylor University Medical Center, Dallas, Texas

7. Wisconsin Center for Advanced Research, Milwaukee, Wisconsin

8. University of Massachusetts Memorial Medical Center, Worcester, Massachusetts

9. Washington Hospital Center, Washington, District of Columbia

10. University of Miami Center for Liver Diseases, Miami, Florida

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