May 8, 2013

Faldaprevir Early Hepatitis C Treatment Success, Viral Cure

Daniel M. Keller, PhD

May 08, 2013

AMSTERDAM, the Netherlands — In this era of interferon-free treatment for chronic hepatitis C virus infection, faldaprevir looks good in combination with pegylated interferon and ribavirin, according to a new study.

The regimen cleared the virus with a short course of treatment and was well tolerated, Peter Ferenci, MD, from the Medical University of Vienna in Austria, told delegates here at the International Liver Congress 2013.

Faldaprevir is a potent selective inhibitor of hepatitis C virus NS3/4A protease, and has antiviral activity against hepatitis C genotypes 1, 2, 4, 5, and 6 in vitro. It can be administered orally once a day.

The phase 3 placebo-controlled trial, called STARTVerso 1, enrolled treatment-naive patients from Europe and Japan with genotype 1 infection and platelet counts above 90,000/mm³. Investigators randomized participants to 1 of 3 groups in a 1:2:2 ratio.

One group took placebo plus interferon alfa-2a 180 μg/week plus weight-based ribavirin for 24 weeks, with an additional 24 weeks of interferon and ribavirin (control group; n = 132). Another group took faldaprevir 120 mg daily for 12 or 24 weeks (guided by response) plus interferon and ribavirin (low-dose group; n = 259). The third group took faldaprevir 240 mg daily for 12 weeks with interferon and ribavirin for the entire 24 weeks (high-dose group; n = 261).

In the 2 faldaprevir groups, patients with early treatment success, defined as a hepatitis C RNA level below 25 IU/mL at week 4 and undetectable at week 8, stopped all treatment at week 24. If there was no early treatment success, patients in the control and low-dose groups continued on interferon and ribavirin out to week 48. The primary end point was a sustained virologic response 12 weeks after the end of therapy.

At baseline, the groups were well balanced; randomization had been stratified by genotype 1 subtype and race. About half the patients were men, about 78% were white, and mean age was about 47 years. In each group, 35% to 41% of the participants were infected with IL28B genotype CC.

Baseline median hepatitis C RNA level was 6.4 log10 IU/mL in each group. About 35% of participants were infected with genotype 1a virus; the rest were infected with genotype 1b. In each group, 6% had cirrhosis and 16% to 19% had fibrosis of stage F3 or higher.

Patients in the 2 faldaprevir groups had significantly better virologic responses 12 weeks after the end of therapy than those in the control group. As has been seen in many other studies, patients with genotype 1b virus had better responses than those with genotype 1a. This effect was most pronounced in the control group.

Table. Sustained Virologic Response 12 Weeks After Therapy

Group Response, % P Value vs Placebo Response in Genotype 1a Patients, % Response in Genotype 1b Patients, %
Control 52 36 60
Low-dose faldaprevir 79 <.001 69 84
High-dose faldaprevir 80 <.001 76 83

The 2 doses of faldaprevir were associated with very similar response rates. "You can get the same effect with the lower dose, thereby limiting potential side effects," Dr. Ferenci told Medscape Medical News.

In the 2 faldaprevir groups, 75% of the patients achieved early treatment success with undetectable virus by week 4, and another 13% had undetectable virus at week 8. Only 12% did not achieve early treatment success. The effect was fairly durable. Of the 88% achieving early success, 86% in the low-dose group and 89% in the high-dose group had a sustained virologic response at 24 weeks.

The Q80K mutation, a resistance mutation in the NS3 protease gene, was found in 23% of the genotype 1a patients. However, in the faldaprevir groups, there was no appreciable difference in the 12-week sustained virologic response between patients with genotype 1a and those with wild-type virus.

The sustained virologic responses in the 2 faldaprevir groups were similar, regardless of the host IL28B genotype. In the control group, response was better in patients with the CC genotype than in those with other IL28B genotypes. "This is not surprising because [the CC genotype] predicts response to interferon, and since this is an interferon-containing regimen, clearly the CC genotype is good," Dr. Ferenci said.

In all subgroup analyses based on virus genotype, patient race, IL28B genotype, fibrosis stage, or baseline hepatitis C RNA level, the effect of low- and high-dose faldaprevir were equivalent.

Excellent Safety and Tolerability

More than 90% of patients in each group experienced an adverse event, but only 4% to 5% in each group discontinued all medication. Serious adverse events affected only 6% to 7%. Anemia was the most frequent adverse event, affecting 11% to 13% of patients in each group. Rash was also common, affecting 6% to 9% of patients.

Rash of at least grade 2, affecting 7% to 9% of patients, was related to ribavirin; besides anemia, there were no hematologic adverse effects related to ribavirin. "This is in sharp contrast to both telaprevir and boceprevir," Dr. Ferenci said, noting that a lot of supportive treatment is needed to keep patients on those drugs.

"The only real side effect unique to this drug and to this whole group of drugs, which includes simeprevir, is the increase in bilirubin." However, this increase is not associated with an increase in liver values, so it is not a liver disease. It is just an inhibition of bilirubin transport without any clinical significance, Dr. Ferenci explained.

In this study, bilirubin elevations, mostly seen with the higher dose, had returned to baseline at 18 weeks. The problem of photosensitivity seen in previous studies was solved by giving subjects a strong sunscreen.

Dr. Ferenci pointed out 2 unique characteristics of this study. First, it involved patients from East Asia as well as Europe. "It's the very first study with triple therapy targeting East Asian patients. And in this short period, they're doing much better," he reported. Second, this study and a previous phase 2 study of faldaprevir involved patients with cirrhosis, whereas most studies exclude these patients. "It worked very well in cirrhotic patients without any safety signals," he explained. Patients with cirrhosis and hepatitis C genotype 1b got a big benefit from this regimen, he noted.

This trial was started in the era before interferon-free regimens had gained traction. Dr. Ferenci said the sponsor will now pursue studies of faldaprevir in combination with other drugs in interferon-free regimens, but this study shows "that this drug is safe and can be used for combination therapy without interferon," although it is not yet approved for any use.

Mark Thursz, MD, from Imperial College London in the United Kingdom, who was not involved in the study, told Medscape Medical News that the criterion of early treatment success is "slightly different" from the usual extended rapid virologic response used in other studies, "and you can see that they met that criterion extremely well."

He also pointed out the very good safety profile exhibited in this trial. "The adverse-event frequency is low in this trial. This is going to be far better tolerated by our patients than the existing protease inhibitors," he predicted.

The study was sponsored by Boehringer Ingelheim. Dr. Ferenci reports being an advisory board member for Boehringer Ingelheim, Roche, MSD, Gilead, Vertex/Tibotec, Idenix, Achillion, Rottapharma-Madaus, and GSK, and receiving unrestricted research grants from Roche Austria and MSD Austria. Dr. Thursz reports relationships with Abbott and Gilead.

International Liver Congress 2013: 48th Annual Meeting of the European Association for the Study of the Liver (EASL). Abstract 1416. Presented April 27, 2013.

Source

Erqou S. J Viral Hep. 2013;doi:10.1111/jvh.12107.

May 8, 2013

Patients coinfected with hepatitis C and HIV are at increased risk for death with the presence of pretreatment anemia, while the initiation of therapy for HCV improves survival in this population, according to recent results.

Researchers evaluated data from 5,000 patients coinfected with hepatitis C and HIV, including 1,671 participants who had anemia before undergoing therapy during a maximum follow-up of 7 years. Data were collected from the Electronically Retrieved Cohort of Hepatitis C-Infected Veterans. All-cause mortality rates were determined and compared between those with and without pretreatment anemia, and between anemic patients who did and did not initiate HCV treatment.

Multivariate analysis indicated significant associations between pretreatment anemia and factors including advanced age (OR=2.1; 95% CI, 1.46-3.03 for every 5 years), African-American race (OR=2.11; 95% CI, 1.79-2.5) and the presence of chronic kidney disease (OR=3.34; 95% CI, 2.8-4), decompensated liver disease (OR=2.56; 95% CI, 2.18-3.01) and cancer (OR=1.64; 95% CI, 1.29-2.09).

Within the cohort, 333 nonanemic patients and 84 with anemia initiated therapy for HCV. Anemic patients were less likely than nonanemic participants to undergo therapy (OR=0.48; 95% CI, 0.37-0.61).

During follow-up, anemic patients had significantly higher mortality rates (144.2 deaths per 1,000 person-years compared with 47.5 among those without anemia), while anemic patients who initiated HCV treatment had lower rates than those who did not (66.6 per 1,000 person-years vs. 149.5). Undergoing therapy for HCV was significantly associated with an improved mortality rate (HR=0.41; 95% CI, 0.29-0.58). Adjustment for covariates, including the presence of multiple comorbidities, did not eliminate the significance of the association (HR=0.36; 95% CI, 0.21-0.62).

“Our study demonstrated that HCV treatment is associated with substantial survival benefit in HCV/HIV coinfected individuals with pretreatment anemia,” the researchers concluded. “The importance of these findings is heightened because this group of patients has significantly higher mortality and lower HCV treatment rates as compared to those without anemia. Further study is needed to find strategies … in optimizing HCV treatment to improve HCV treatment rates among this group.”

Source

No Toxicity, Possible Cancer Benefit With Statins and HCC

Nick Mulcahy

May 08, 2013

In adults with hepatitis C virus (HCV) infection, statin use is associated with a significantly reduced risk for hepatocellular carcinoma (HCC), according to a large observational study from Taiwan.

"Statin use is a convenient and acceptable adjuvant strategy for preventing HCC in HCV-infected patients," conclude the authors, led by Yu-Tse Tsan, MD, from the National Taiwan University in Taipei.

The virus increases the risk of developing liver cancer 15- to 20-fold, they point out.

This is the first large population-based study to look at statin use and the risk for HCC, Dr. Tsan and colleagues note. Their results, from more than 260,000 HCV-infected patients, were published in April 20 in the Journal of Clinical Oncology.

Results from previous observational studies and randomized controlled trials of statins have been mixed on their protective effect for HCC, they say.

This is the first study to document a dose–response relation between statin use and the risk for HCC in HCV-infected patients. The authors found that, over a 12-month period, the greater the daily statin use, the greater the reduction in cancer risk.

When statin use was compared with no use, for an annual cumulative defined daily dose (cDDD) of 28 to 89, the adjusted hazard ratio was 0.66; for a cDDD of 90 to 180, it was 0.47; and for a cDDD above 180, it was 0.33.

The risks were calculated after controlling for a variety of confounders (age, sex, income, urbanization, liver cirrhosis, and diabetes) in 35,023 statin users and 225,841 nonusers.

In an accompanying editorial, Abby Siegel, MD, from the Columbia University Medical Center in New York City, praises the results as "compelling evidence" for an association between statin use and a significantly lower risk for HCC..

But she does not agree that statins are ready for this clinical use. "It is too soon to recommend off-label use of statins for HCC prevention," she writes.

"We need better insight into where in the spectrum of liver disease statins might work best and the appropriate duration of treatment," Dr. Siegel adds.

Liver Toxicity

The biggest contribution of this study might be the evidence that statins are not toxic in HCV-infected patients, Dr. Siegel notes.

"There was no increase in hepatotoxicity seen with use of statins in patients with underlying HCV, which has been a concern about using these agents in patients with liver disease," she writes. In fact, the adjusted hazard ratios for myotoxicity and drug-induced liver injury were nonsignificant (1.08 and 1.30, respectively) for patients with 90 days of regular statin use.

With these results, "we can feel more confident that statins do not cause harm in patients with liver disease," she says.

Dr. Siegel is impressed with 2 other aspects of this study. "The results were statin specific, and were not seen with other lipid-lowering agents," she writes. In addition, the follow-up in this observational study was "relatively long, at just over 10 years." This is important because no association has been found between statin use and reduced risk for HCC in HCV-infected patients in randomized controlled trials, she notes. The implication of her comments is that, although randomized controlled trials are the gold standard for clinical evidence, they are not usually very long and therefore could miss a treatment effect.

Dr. Siegel begins her criticism of the study in a predictable place — saying that observational studies are "susceptible to bias."

Most notably, she says, because the differences between the user and nonuser groups are seen so quickly (after a cDDD of just 28 to 89), "one might suspect that other nonbiologic factors are playing a role."

Clinical trials of statins in this setting are needed, Dr. Siegel concludes. But they would be expensive to conduct because of the large numbers of patients that would be required. As a possible solution, she proposes the use of surrogate markers to better determine just where in the continuum of liver disease (leading to liver cancer) statins have an effect.

The study authors and Dr. Siegel have disclosed no relevant financial relationships.

J Clin Oncol. 2013;31:1514-1521 and 1499-1501. Abstract, Editorial

Source

Clin Infect Dis. 2013 Apr 22. [Epub ahead of print]

Witt MD, Seaberg EC, Darilay A, Young S, Badri S, Rinaldo CR, Jacobson LP, Detels R, Thio CL.

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.

Abstract

Background. Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)-infected and -uninfected men who have sex with men (MSM) over the entire HIV epidemic has not been comprehensively conducted. Methods. To determine the trends in and risk factors associated with incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)-negative MSM in the Multicenter AIDS Cohort Study were prospectively followed during 1984-2011 for anti-HCV seroconversion. Results. During 55 343 person-years (PYs) of follow-up, there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered throughout the study period. In a multivariable analysis with time-varying covariates, older age (incidence rate ratio [IRR], 1.40/10 years, P < .001), enrollment in the later (2001-2003) recruitment period (IRR, 3.80, P = .001), HIV infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR, 1.68, P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001), syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with >1 male partner (IRR, 3.37, P < .001) were independently associated with incident HCV. Among HIV-infected subjects, every 100 cell/mm3 increase in CD4 count was associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4 count of 500 cells/mm3, whereas there was no association with highly active antiretroviral therapy. Conclusions. The spread of HCV among both HIV-infected and -uninfected MSM in the United States has been ongoing since the beginning of the HIV epidemic. In HIV-infected men with <500 CD4+ T cells, the HCV incidence rate was inversely proportional to CD4 T-cell count.

Source

Press Release

Embargoed Until: Tuesday, May 7, 1:30 PM EDT 2013,
Contact: National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
NCHHSTPMediaTeam@cdc.gov; 404-639-8895

Study suggests only half of Americans with hepatitis C receive complete testing for the virus

CDC reinforces need for appropriate follow-up testing for current infection

Only half of Americans identified as ever having had hepatitis C received follow-up testing showing that they were still infected, according to a Centers for Disease Control and Prevention analysis of data from a multi-area study published today in the CDC report Vital Signs.

“Many people who test positive on an initial hepatitis C test are not receiving the necessary follow-up test to know if their body has cleared the virus or if they are still infected,” said CDC Director Tom Frieden, M.D., M.P.H. “Complete testing is critical to ensure that those who are infected receive the care and treatment for hepatitis C that they need in order to prevent liver cancer and other serious and potentially deadly health consequences.”

Testing for hepatitis C includes a blood test, called an antibody test, to determine if an individual has ever been infected with the virus. For people with a positive antibody test result, a follow-up test – called an RNA test – should be given to determine whether they are still infected so they can get needed care and treatment.

A small number of people with antibody-positive tests will have cleared the infection on their own, but most people with hepatitis C (about 80 percent) remain infected and can go on to develop significant health problems.

For the Vital Signs study, researchers looked at data from eight areas across the nation funded by CDC to conduct enhanced surveillance for hepatitis C virus infection. Of the hepatitis C cases reported in these areas (i.e., those cases with antibody-positive results), only 51 percent of the cases also included a follow-up (RNA) test result that identified current infection. Without follow-up testing, the other half are likely unaware if they are currently infected and therefore cannot get appropriate medical care.

Data included in this analysis also underscore the severe impact of hepatitis C among baby boomers. In the eight areas studied, 67 percent of all reported cases of current infection were among those born from 1945 through 1965. Deaths among people with hepatitis C also were more common among those born during these years (accounting for 72 percent of all reported deaths).

“Hepatitis C has few noticeable symptoms, and left undiagnosed it threatens the health of far too many Americans – especially baby boomers,” said John Ward, M.D., director of CDC’s Division of Viral Hepatitis. “Identifying those who are currently infected is important because new effective treatments can cure the infection better than ever before, as well as eliminate the risk of transmission to others.”

Overall, approximately 3 million Americans are infected with hepatitis C and up to 3 out of 4 do not know they are infected. The vast majority of those affected are baby boomers, or those born from 1945 through 1965. Left untreated, hepatitis C can cause serious liver damage, including liver cancer. Hepatitis C is a leading cause of liver cancer and the most common indication for liver transplants. In fact, liver cancer is the fastest-rising cause of cancer-related death in the United States. Deaths from hepatitis C have nearly doubled over the past decade, now accounting for more than 15,000 deaths each year.

In light of increasing evidence that many patients are not receiving the follow-up test, as well as recent changes in testing technologies and the availability of new effective treatments for hepatitis C, CDC is issuing updated guidance for health care providers on hepatitis C testing. These guidelines reinforce the recommended process for hepatitis C testing and underscore the importance of providers conducting follow-up RNA testing for all patients with a positive antibody test result in order to help ensure people infected with hepatitis C are properly tested and identified.

CDC recommends that everyone in the United States born from 1945 through 1965 be tested for hepatitis C. CDC also recommends that other populations at increased risk for hepatitis C get tested, including those who received blood transfusions or organ transplants before widespread screening of the blood supply began in 1992, or those who have ever injected drugs.

This Vital Signs coincides with Hepatitis Awareness Month and National Hepatitis Testing Day on May 19.

More information is available at www.cdc.gov/nchhstp/newsroom.


Press Briefing Transcript

 

CDC Telebriefing on Hepatitis C testing

May 7, 2013 1:30 pm E.T.

Audio recording Audio/Video file [MP3, 4.01MB]

OPERATOR: Good afternoon and thank you all for standing by. This is the conference coordinator. All lines will be placed on listen only until we're ready for the question and answer session of today's call. This call is also being recorded. If you do have any objections, you may disconnect at this time. I would now like to introduce your first speaker, Mr. Tom Skinner. You may begin, sir. Thank you.

TOM SKINNER: Thank you, Lori. And thank you all for joining us today for another release of a CDC vital signs. This one is on the evaluation of Hepatitis C virus infection, testing and reporting. Eight US Cities 2005 to 2011. Today we're joined by the director of the CDC, Dr. Tom Frieden, who will provide some opening remarks. And then we'll turn the call over to Dr. John Ward who is the director of our division of viral hepatitis who will provide some further detail on the report. And then we will get to your questions. So without further ado, I’d like to turn the call over to CDC director tom Frieden.

TOM FRIEDEN: Good afternoon, everyone. Welcome and thanks very much for joining the call. Hepatitis C affects about 3 million Americans, about 3 million people infected. Most of the infected people in this country are baby boomers. Born between the years 1945 and 1965. The bottom line here is, if you were born between those years, get tested. And if you're positive, get follow-up testing. Before I head into details, really the take-home message from today's report is that you may not remember everything that happened in the '60s and '70s, but your liver does. And for that reason, everyone from 45 to 65 should be tested and should get complete testing. Once someone's infected with Hepatitis C, about four out of five, 80 percent, stay infected for life. The 3 million people today infected with Hepatitis C, about half will go on to have serious liver problems known as cirrhosis and about one-third may die from complications of their infection. That's one million people, potentially dying from Hepatitis C unless we effectively address it. Hepatitis C is the most common reason people need liver transplants. And it's the leading cause of liver cancer which is the fastest rising cause of cancer-related death in the U.S at CDC we estimate that if baby boomers get tested and if they're infected, get into care, we could prevent at least 100,000, about 120,000 deaths. Now, getting into some of the details of today's report, we were able to track Hepatitis C in eight US Sites, eight cities, from 2005 to 2011. And although many people were found to be positive, it appears that only about half had complete testing for the virus, meaning that following an initial test, they had follow-up testing. With Hepatitis C, you really need two stages of testing. The first test, a screen to see if you've ever been infected with the virus. And the second see whether you're still infected or whether you're one of the fortunate 20 percent that isn't still infected. Today's data show that even among young people who get tested positive, only about half had follow-up tests to see if they were still infected. That's what you need to get appropriate care and treatment. Right now there are better Hepatitis C treatments available than ever and there are more treatments coming in the coming year. So confirming that someone is more infected is more important than ever. Not everyone with Hepatitis C will need treatment, but everyone with Hepatitis C should be linked to care so that they can monitor how their liver is doing, determine when and if treatment is warranted, avoid things like excess alcohol which can damage their liver, and avoid medications that could also damage their liver as well as getting vaccinated against hepatitis b to protect their liver. Liver disease is something which is causing an increasing number of deaths, and many of those deaths could be prevented with the current treatments and with preventive actions that people can take if, but only if, they know that they're infected. Today CDC is also issuing updated guidance for doctors and other health care providers about how to test for Hepatitis C and how to provide follow-up. And Dr. Ward will provide more detail on that in his remarks. Before I turn the call over to Dr. Ward, I’ll be back with you for questions; I want to remind baby boomers to get tested for Hepatitis C. And if your screening test is positive, make sure you go back for a follow-up test. We have key messages in the vital signs for patients, for health care providers, for health care systems and for state and local governments, all of which can play an important role in reducing the risks that people will progress from Hepatitis C infection to severe liver disease, because it's possible to stop that progression. So, again, baby boomers may not remember everything we did in the '60s or '70s, but our liver does. Get tested to find out if you have the infection now, because if so, care and treatment really could save your life. Now, Dr. Ward?

DR JOHN WARD: Thanks, Tom and good afternoon, everyone. This is Dr. John Ward, the director of the division of hepatitis here at CDC. Today's report is based on an analysis of data from 2005 through 2011 reported by eight states in major cities across the country that received CDC funding to conduct enhanced surveillance for Hepatitis C. As Dr. Frieden just remarked, today's findings suggest that when people test positive for Hepatitis C ant bodies, the follow-up test is often not completed. The report found that among those individuals who received a positive antibody test, only half, 51 percent, also had a positive follow-up test reported to the health department that indicated that they were still infected. We already know there's a majority of those with Hepatitis C do not know that they're infected because they haven't been tested. These data suggest that even among individuals who have received that initial antibody test, as many as half do not know for sure if they still carry the virus. So what happened to the other half? They only had a positive antibody test? Some of these individuals may have cleared the infection on their own because we know that about 20 percent of persons who become infected with Hepatitis C will clear that infection on their own. So we believe that the larger portion of persons without a positive test, only a small proportion of those fall into this category. More importantly, we believe it's likely that most of these individuals are still infected with Hepatitis C but have not received that follow-up test necessary to confirm their infection and serve as a gateway to them receiving the care and appropriate treatment they need. Our findings add to other previous research which also has suggested that a substantial proportion of those with Hepatitis C antibodies, give us an idea of the gap between those who are and are not receiving the test and show us that we have a substantial challenge in front of us. Updated Hepatitis C testing guidance published today by CDC reinforces our current recommendations and underscores the importance of follow-up testing for everyone who tests positive for HCV antibodies. This reinforces CDC guidance published last year. We are hopeful that the percentage of cases reported RNA test results has already begun to increase since that time. We strongly urge all health care providers to implement Hepatitis C testing including the appropriate follow-up testing necessary to identify current infection with Hepatitis C.

TOM SKINNER: Lori, I believe that we're ready for questions. Could you please provide instructions for asking questions, please?

OPERATOR: Thank you, sir. We will now begin the question and answer session. If you would like to ask a question, please press star-one. You will be prompted to record your name. Press star-two to withdraw your request. One moment for the first question. Our first question comes from Michelle Meryl with the Hospital Employee Health Newsletter.

MICHELLE MERYL: Thank you very much for taking my question. So I had a question about health care workers. I know they're at risk for Hepatitis C, and they may be at risk for exposures from patients who have -- who are unknown -- it's unknown whether they have Hepatitis C. So I guess a couple-tiered question, will you have guidelines for management of health care workers with Hepatitis C as you do for hepatitis B? Are you recommending any special testing in a hospital setting, either of patients when they're admitted or of any kind of routine testing of health care workers who are involved in exposure-prone procedures?

TOM FRIEDEN: Dr. Ward, why don't you take that question?

DR. JOHN WARD: CDC has guidelines already for the management of health care workers with Hepatitis B, HIV and Hepatitis C. And so those are our current recommendations which stipulate the type of management that's indicated. The second part of that question regarding testing of patients as they come in, I think that really brings up the different settings or strategies that are -- could be brought to bear to put CDC's recommendations into implementation so that -- and so we have actually funded about 25 to 30 -- what we call demonstration sites to test out, what are the best ways to make testing available so that you reach the person's recommending and who can benefit from testing in a more efficient and effective way possible. So to your point, some hospitals that we're working with are beginning to implement routine screening in the emergency department. Some of them are experimenting with what's called physician reminders so that when someone checks into the clinic within this date of birth span, a reminder will pop up electronically, indicating that person is recommended for testing. And then there are various other strategies that health care providers are working with. But that's a critical piece. That to be effective, you have to have your policy put into operation, and that's why we're trying to develop best practices for and working with our partners around the country.

MICHELE MARILL: So if I could just follow up. So you're not going to update or change anything with regard to your recommendations specifically for health care workers?

JOHN WARD: That’s correct.

TOM SKINNER: Next question, Lori?

OPERATOR: Our next question comes from Robert Lowes with Medscape Medical News.

ROBERT LOWES: Yes, thanks for taking my call. I wanted to clarify something in the MMWR and in the press release, it says that of these 218,000 people, 49% just had the -- or tested positive on the antibody test. And then 50.8% were reported with a positive RNA test. Is it the case that the people that went beyond the antibody test, is it safe to construe that almost 51% went beyond getting the antibody test and then all of them turned out to be positive based on the RNA results? It's hard for me to put my head around how you're trying to express that. Because it sounds like that, you know, half the people, you know, tested positive in terms of the antibody test. But then the rest went on -- and of that group, half went on to get the RNA test, and they all were positive.

TOM FRIEDEN: Why don't we try to clarify that for you.

ROBERT LOWES: Yeah.

TOM FRIEDEN: And Dr. Ward can explain further. Among the universe of people who tested positive for the antibody, only 50%, only half, had any record reported to their health department that they had a follow-up test. So of those who were positive by antibody, only 50% had the recommended follow-up RNA reported. Dr. Ward, you want to say anything further?

JOHN WARD: No, I think that's -- I mean, I agree with that -- I don't know if there's a follow-up to that.

ROBERT LOWES: But in other words, the people who had the just antibody test, it really wasn't clear whether they harbored the virus because it just showed that at one point, they had the virus, but it did not show that they were -- they still had the virus, right?

TOM FRIEDEN: That’s right. What we know from many other studies is about 80% of them probably still did. So it's concerning that it looks like about half didn't have the follow-up testing since the great majority of them probably had continued infection and may not have gotten the required testing, or recommended testing, I should say.

JOHN WARD: I think, you know, both sides of this proportion really lead you to the same conclusion, and that is the testing for viremia is very important. You have to know -- the most important question to be answered by Hepatitis C testing is am I currently infected with this virus and have this condition? And that second test has to be conducted to answer that question.

TOM SKINNER: The next question, Lori?

OPERATOR: Our next -- as a reminder, if you would like to ask a question, please press star-one. You will be prompted to record your name. And our next question comes from Christopher Yi with Hartford Health.

CHRISTOPHER YI: Hi. We have a question here in regards to after the initial screening, how far after do you recommend a follow-up? Testing?

TOM FRIEDEN: Dr. Ward?

JOHN WARD: Well, I think we really -- we just recommended it be done. You know, at any time, obviously, the sooner, the better. But we don't put a time limit beyond which it's no longer helpful. This is a chronic infection that, you know, that lasts really essentially over the course of a lifetime once it's established. So that testing needs to happen. We would like for it to happen promptly. But we want it to happen in any case.

TOM SKINNER: Next question, Lori?

OPERATOR: Our next question comes from Liz Highleyman with hivandhepatitis.com.

LIZ HIGHLEYMAN: Yes, thank you for taking my question. I'd like to see if Dr. Frieden can clarify the percentages of people who turn out to be chronically infected with Hepatitis C who have -- who have gone on to develop cirrhosis, liver cancer and liver related early death. I know you gave a figure, but I didn't catch it.

TOM FRIEDEN: It’s about 37%. Is that correct, Dr. Ward?

JOHN WARD: About 37%, we estimate, will die of Hepatitis C related complications such as the ones the caller described over the course of a lifetime. And about -- we estimate of the 3 million Americans currently living with Hepatitis C now, about half will develop cirrhosis.

LIZ HIGHLEYMAN: Thank you.

TOM SKINNER: Next question, Lori?

OPERATOR: Sir, thank you. That was our last question. I'll turn the call back over to you.

TOM SKINNER: Dr. Frieden, would you like to close our call with some closing remarks, please?

TOM FRIEDEN: Sure. I would just first thank you all for being a part of this call. Remind us that 3 million people is a lot of people to have an infection which will seriously harm many of their health. That three out of four of them don't know they're infected. And even many of the people who have been tested don't appear to have gotten follow-up testing. So we have a lot more that we can do and need to do to make sure that we're protecting people as well as possible from serious illness and death from Hepatitis C, cirrhosis and liver cancer, in particular. So, again, if people born from '65 -- I’m sorry, from 1945 to 1965 may not remember everything that happened in the '60s and '70s, but their liver does. And so it's very important to get complete testing for Hepatitis C. For health care providers, it's very important to put in automatic systems to make sure that if someone has a positive antibody test, they go on to have follow-up testing and then get into care so they can avoid further liver damage, and if appropriate, get treated. And I want to thank you all very much for joining us.

TOM SKINNER: Thank you, Lori. And this concludes our call. If you have follow-up questions or need additional information on hepatitis or this particular Vital Signs, please call our hepatitis media office at 404-639-8895. Thanks again for joining us.

OPERATOR: Thank you. That does conclude today's conference call. Thank you all for joining. You may disconnect at this time.

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SAN DIEGO, May 7, 2013 /PRNewswire/ -- Aethlon Medical, Inc. (OTCQB: AEMD), today released the following note authored by its Chairman and CEO, Jim Joyce .

Through the publication of CEO notes, I seek to provide shareholders and other interested parties with a level of corporate transparency often absent in the microcap marketplace. In recent notes, I reviewed various topics, including emerging opportunities in cancer and the expansion of our government contract program to create a sepsis therapeutic.

This note is specific to our most important near-term objective: the approval of a investigational device exemption (IDE) by the U.S. Food and Drug Administration (FDA) that would allow us to initiate clinical feasibility studies of Hepatitis-C (HCV) infected individuals receiving Hemopurifier® therapy. In this regard, FDA withheld clearance of our recently amended IDE based on a single information deficiency that was deemed a safety concern. Specifically, FDA has requested that we detail our training and monitoring procedures related to heparinization, which is the primary anticoagulant utilized in dialysis and other extracorporeal therapies, including our Hemopurifier®. We are assembling the requested information and expect to have our response back in the hands of FDA in the coming week. The approval of our IDE remains a critical step in our strategy to advance a first-in-class medical device to address a major-market infectious disease condition.

HCV is a blood-borne pathogen that affects upwards of 170 million persons, or 2-3% of the world's population. It is a leading cause of liver cirrhosis and transplant and there is no pre or post infection vaccine. The magnitude of the HCV therapeutic opportunity has spawned immense competition within the drug industry. According to citeline®, there are over 200 planned and ongoing Phase I-III trials of pipeline HCV drugs as of March 1, 2013. However, it should be noted that only ten companies are responsible for 83% (165/200) of the referenced HCV studies; Bristol-Myers Squibb, Gilead, Merck & Co., AbbVie, Boehringer Ingelheim, Johnson & Johnson, Roche, Vertex, Achillion and Novartis. A primary factor for this odd statistical imbalance is the reality that these organizations often acquire candidate therapies that demonstrate clinical promise.

As a medical device, we have an enduring opportunity as our Hemopurifier® is uniquely positioned as an adjuvant to either interferon-based standard of care (SOC) or emerging all-antiviral drug regimens. And, unlike adjunct drug strategies, the Hemopurifier® performs without adding drug toxicity. In studies conducted in India, a three-treatment Hemopurifier® protocol administered in combination with interferon-based SOC resulted in undetectable HCV levels in as little at seven days in hard to treat genotype-1 patients. The studies also documented the ability of the Hemopurifier® to capture as many as 300 billion copies of HCV during a single six-hour treatment. In addition to augmenting the early viral kinetic response to drug therapy, the Hemopurifier® is a candidate solution for viral rebound patients who traditionally are forced to discontinue therapy once HCV establishes resistance to their drug regimens. Such a solution would address a significant unmet medical need in HCV care.

In closing, we are confident that we can fulfill FDA's information request. In the interim, I remain grateful to loyal shareholders that support our cause and I salute the continued perseverance of my Aethlon teammates.

About Aethlon Medical

Aethlon Medical creates innovative medical devices that address unmet medical needs in cancer, infectious disease, and other life-threatening conditions. Our Aethlon ADAPT™ System is a revenue-stage technology platform that provides the basis for a new class of devices the rapid, yet selective removal of disease promoting particles from the entire circulatory system. At present, The Aethlon ADAPT™ product pipeline includes the Aethlon Hemopurifier® to address infectious disease and cancer, and a medical device being developed under a 5-year contract with Defense Advanced Research Projects Agency (DARPA) to reduce the incidence of sepsis in combat-injured soldiers. For more information, please visit www.aethlonmedical.com.

About The Aethlon Hemopurifier®

The Aethlon Hemopurifier® is a first-in-class medical device that selectively targets the rapid clearance of infectious viral pathogens and immunosuppressive proteins from the entire circulatory system. In the treatment of Hepatitis C virus (HCV), human studies have demonstrated that Hemopurifier® therapy may improve immediate, rapid and sustained virologic response rates when administered in the first few days of standard-of-care drug therapy. In addition to accelerating viral load depletion, post-treatment analysis of the Hemopurifier® has documented the capture of up to 300 billion HCV copies of HCV during a single six-hour treatment. Access to Hemopurifier® therapy is available on a compassionate-use basis through the Medanta Medicity Institute (Medicity), a leading center for medical tourism in India. The Medicity is offering treatment access to infected individuals who previously failed or subsequently relapsed standard-of-care drug regimens. The Hemopurifier® is also being offered as a salvage therapy to infected individuals who suffer a viral breakthrough during standard-of-care therapy. U.S. studies of the Hemopurifier® are currently pending approval of an IDE submitted to FDA.

The Aethlon Hemopurifier® and Cancer

In addition to the opportunity to address a broad-spectrum of infectious viral pathogens, the Hemopurifier® has been discovered to capture tumor-derived exosomes underlying several forms of cancer. Tumor-derived exosomes have recently emerged to be a vital therapeutic target in cancer care. These microvesicular particles suppress the immune response in cancer patients through apoptosis of immune cells and their quantity in circulation correlates directly with disease progression. Beyond possessing immunosuppressive properties, tumor-derived exosomes facilitate tumor growth, metastasis, and the development of drug resistance. By addressing this unmet medical need, the Hemopurifier® is positioned as an adjunct to improve established cancer treatment regimens.

Certain statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc. to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, that the FDA will not approve the initiation of the Company's clinical programs or provide market clearance of the company's products, future human studies whether revenue or non-revenue generating from either compassionate use or non-compassionate use of the Aethlon ADAPT™ system or the Aethlon Hemopurifier® as an adjunct therapy to improve patient responsiveness to established cancer or hepatitis C therapies or sepsis therapies or as a standalone cancer or hepatitis C therapy or standalone sepsis therapy, the Company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the Company's ability to manufacture its products either internally or through outside companies and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

Contacts:

James A. Joyce
Chairman and CEO
858.459.7800 x301
jj@aethlonmedical.com

Jim Frakes
Chief Financial Officer
858.459.7800 x300
jfrakes@aethlonmedical.com

Marc Robins
877.276.2467
mr@aethlonmedical.com

SOURCE Aethlon Medical, Inc.

RELATED LINKS
http://www.aethlonmedical.com

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Chicago Boomers Face Silent Hepatitis C Virus Risk

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MedSpring Immediate Care offers free screenings in May.

Austin, TX (PRWEB) May 07, 2013

Many baby boomers’ bodies may be harboring a silent killer: Hepatitis C. In fact, the federal Centers for Disease Control (CDC) recommends testing for anyone born between 1945 and 1965 as early diagnosis and treatment can help prevent liver damage, cirrhosis, liver cancer and other complications.

In recognition of Hepatitis Awareness month, MedSpring is offering baby boomers, those born between 1945-1965, free Hepatitis C screenings at any of its 14 centers in Chicago, Austin and Houston during the month of May. In addition, those born after 1965 with tattoos and body piercings are also eligible for free screenings.

The Hepatitis C virus is a contagious, blood-borne infection affecting the liver. Baby boomers may have contracted the disease numerous ways, including through a simple blood transfusion, injection drug use or an organ transplant performed prior to 1992. While baby boomers comprise only 27 percent of the U.S. population, the CDC estimates they account for 75 percent of the Hepatitis C cases and 73 percent of deaths related to the virus.

“This simple, one-time blood test can mean the difference between life-saving treatment and serious, even deadly, liver disease,” said Dr. Jon L. Belsher, M.D., MedSpring’s Chief Medical Officer. “The Hepatitis C virus is dangerous, especially to baby boomers, as it can go unnoticed for years with most people experiencing no symptoms.”

MedSpring centers will administer the complimentary blood test to the first 1000 eligible patients during regular center hours of 9am-9pm daily. For those patients requiring follow-up, MedSpring will provide complimentary consultation and referrals. Walk-ins are welcome, and appointments are also available. For more information, visit the Hepatitis C information page on MedSpring’s website.

MedSpring Immediate Care has three centers in Chicago, six in Austin, and five in Houston.

About MedSpring Immediate Care
MedSpring’s 14 Immediate Care centers focus on delivering quality care and exceptional service. For more information, including patient reviews and savings compared to an ER, please visit http://www.medspring.com or find us on Facebook and Twitter.

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Clin Gastroenterol Hepatol. 2013 Apr 16. pii: S1542-3565(13)00482-5. doi: 10.1016/j.cgh.2013.03.032. [Epub ahead of print]

Chen EY, Sclair SN, Czul F, Apica B, Dubin P, Martin P, Lee WM.

Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, TX; Department of Medicine, Division of Hepatology, University of Miami Miller School of Medicine, Miami, FL.

Abstract

BACKGROUND & AIMS: Protease inhibitor triple therapy for hepatitis C virus (HCV) infection (boceprevir or telaprevir with pegylated interferon and ribavirin) has been shown to increase rates of sustained virologic response in phase 3 trials. We investigated the proportion of patients who began therapy with this regimen in the 12 months following the Food and Drug Administration (FDA) approval of boceprevir and telaprevir in the US.

METHODS: We performed a retrospective cross-sectional study of 487 patients with HCV genotype 1 infection (396 did not receive triple therapy and 91 had begun triple therapy with boceprevir or telaprevir), seen at hepatology practices in Dallas and Miami from June 2011 through February 2012. The subjects were predominantly middle-aged, non-Hispanic white, and privately insured; 50% were treatment-naïve, and most had advanced fibrosis. We compared features of patients who initiated triple therapy with those who deferred it. Treated patients were followed to determine the discontinuation rate in the first 12 weeks of treatment.

RESULTS: Of patients assessed, only 18.7% began triple therapy-the same percentage as those receiving dual therapy (pegylated interferon and ribavirin) before boceprevir or telaprevir were approved for treatment of HCV infection in the US. Reasons for deferring treatment included relative contraindications (50.5%), patient choice (22.5%), and less-advanced liver disease (17.4%). Among treated patients, 15% discontinued prematurely because of serious adverse events. Based on multivariate analysis, factors associated with initiation of triple therapy included prior treatment relapse (odds ratio [OR] 4.6; 95% confidence interval [CI], 2.1-9.9) and liver fibrosis of stage 3 (OR, 9.1; 95% CI, 3.1-27) or stage 4 (OR, 9.0; 95% CI, 3.3-25) but not hepatic decompensation.

CONCLUSION: Only 18.7% of patients with HCV genotype 1 infection received triple therapy in the 12 months following FDA approval of boceprevir and telaprevir. This low percentage might result from concerns of side effects and recognition that more effective medications could be available in the future.

Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

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