Friday, January 4, 2013

Gilead Sciences to Present at the 31st Annual JPMorgan Healthcare Conference

Gilead Sciences to Present at the 31st Annual JPMorgan Healthcare Conference on Monday, January 7
Webcast Available Through Gilead Corporate Website
FOSTER CITY, Calif.--(BUSINESS WIRE)--Jan. 4, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that its corporate presentation will be webcast from the 31st Annual JPMorgan Healthcare Conference in San Francisco.
John C. Martin, PhD, Gilead’s Chairman and Chief Executive Officer, will provide an overview of the company on Monday, January 7 at 3:30 p.m. Pacific Time (6:30 p.m. Eastern Time).
To access the live webcast or a replay via the internet, log on to Please connect to the company’s website at least 15 minutes prior to the start of the presentation to ensure adequate time for any software download that may be necessary to listen to the webcast. The replay will be available for 14 days following the presentation.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
For more information on Gilead Sciences, please visit or call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235).

Thursday, January 3, 2013

Hepatitis C - 2013 Interferon Free Combinations

Website Updates

2013 Interferon Free Combinations

Achillion: Poised For Growth And Now Is The Time To Buy
What is notable is that Achillion has 4 drugs in the mix; ACH-2684, 2928, 3102 and 1625. Each of which are showing strong promise at various phase I and II trials, and can either work independently or in combination in an oral fashion, not injections.

2013 Sofosbuvir (GS-7977)

The following two downloads are provided via NATAP's mailing list
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Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
The standard treatment for hepatitis C virus (HCV) infection is interferon,which is administered subcutaneously and can have troublesome side effects.We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.
Download Full Text Here

Exploratory Study of Oral Combination Antiviral Therapy for Hepatitis C
There is a need for interferon-free treatment regimens for hepatitis C virus (HCV) infection. The goal of this study was to evaluate ABT-450, a potent HCV NS3 protease inhibitor,
combined with low-dose ritonavir (ABT-450/r), in addition to ABT-333, a nonnucleoside NS5B polymerase inhibitor, and ribavirin, for the treatment of HCV infection
View PDF ---
nejmoa1208809.pdf 466K View
nejmoa1208809_appendix-1.pdf 115K View
nejmoa1208809_appendix.pdf 115K View

Chronic Hepatitis C Infection: Treat Now or Wait?

2013-Hepatitis C Full Text Articles

2013-HCV Abstract Corner

HCV Advocate - Top News of 2012
A milestone—GS-7977
Outbreaks of HCV in Health Care Settings
First National Helpline
DAA’s and Transplant Patients
and more........

In The News

Microbiotix Announces Exclusive Worldwide Licensing Agreement for HCV NS5B Non-Nucleoside Polymerase Inhibitors

Revolutionary techniques could help harness patients' own immune cells to fight disease

Microbiotix Announces Exclusive Worldwide Licensing Agreement for HCV NS5B Non-Nucleoside Polymerase Inhibitors

Microbiotix Announces Exclusive Worldwide Licensing Agreement for HCV NS5B Non-Nucleoside Polymerase Inhibitors

03 Jan 2013
WORCESTER, MA, USA I January 2, 2013 I Microbiotix, Inc., a privately-held, clinical stage biopharmaceutical company engaged in the discovery and development of novel small molecule anti-infective drugs, announced today that it has entered into an exclusive licensing agreement with Merck, known as MSD outside the United States and Canada.

As part of this agreement, Microbiotix gains worldwide rights to develop, manufacture and commercialize MBX-700 and MBX-701 (formerly SCH 900942 and SCH 900188), two non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase. MBX-700 is in Phase I clinical testing and MBX-701 is currently in preclinical development. Merck is eligible for milestone payments during development stages of the candidates, and for royalty payments from any resulting products. Specific terms of the agreement were not disclosed.

MBX-700 and MBX-701 are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase, a clinically validated target that is essential for viral genome replication. In vitro studies have shown MBX-700 to be among the most potent HCV NS5B polymerase inhibitors.
"This agreement with Merck significantly strengthens our antiviral portfolio," said Terry L. Bowlin, PhD, President & CEO, Microbiotix. "We believe MBX-700 and MBX-701 have great potential as potent ingredients in future combination drug therapy. Our preclinical studies have demonstrated high potency while the Phase I clinical study has shown MBX-700 to be safe and well-tolerated."

"Merck remains committed to the development of therapies for the treatment of hepatitis C," said Eliav Barr, vice president, Infectious Diseases Project Leadership and Management, Merck Research Laboratories. "Our discovery programs have identified a number of well-characterized candidates targeting hepatitis C. Outlicensing deals, such as this one, allow Merck to harness potential value from these assets while ensuring they are developed to their full potential."

About Hepatitis C
Hepatitis C, which primarily affects the liver, is an infectious disease caused by the hepatitis C virus (HCV). HCV infection becomes chronic in 75%-85% of cases and, if left untreated, can lead to chronic liver disease, liver cancer or death. It is estimated that 170 million people worldwide are chronically infected with the hepatitis C virus.

About Microbiotix, Inc.
Microbiotix, Inc., located in Worcester, MA, is a biopharmaceutical company focused on the discovery and development of proprietary small molecule drugs that target serious infectious diseases. The Company's lead therapeutic compound, MBX-700, is a non-nucleoside inhibitor of the HCV NS5B polymerase. In vitro studies have shown MBX-700 to be among the most potent HCV polymerase inhibitors. MBX-700 is in Phase I clinical testing. MBX-701, a non-nucleoside inhibitor also targeting the HCV NS5B polymerase, is in preclinical development. The Company's second clinical compound, MBX-400, a novel agent for the treatment of human cytomegalovirus, is also in Phase I clinical testing.

SOURCE: Microbiotix

HCV Studies Give Hope for Interferon-Free Therapy

HCV Studies Give Hope for Interferon-Free Therapy

Interferon-Free Therapies for Hep C Virus Look Promising

New Pills Show Promise for Hepatitis C

If approved, they'll provide fewer side effects, shorter treatment time, studies suggest

WEDNESDAY, Jan. 2 (HealthDay News) -- Two new pills on the horizon for people with hepatitis C promise shorter treatment time and fewer side effects than today's standard treatment, interferon.
The first treatment studied combines a drug currently called ABT-450/r and one called ABT-333. Together, these drugs achieved up to a 95 percent sustained response, meaning the drugs suppressed levels of hepatitis C in the blood over time.

The second drug, called sofosbuvir, when combined with the currently used medication ribavirin, induced a 100 percent sustained response rate, the researchers found.

Both drugs require just 12 weeks of treatment compared to today's standard of 48 weeks, according to the authors.

"Over the next few years, we're going to have several new options to eradicate the hepatitis C virus," said the lead author of the ABT-450/r study, Dr. Fred Poordad, a professor of medicine at the University of Texas Health Science Center in San Antonio.

"We're hopeful that in the next 10 years, we should be able to eradicate hepatitis C in most Americans," said Poordad.

Both studies appear in the Jan. 3 issue of the New England Journal of Medicine. The ABT-450/r study was funded by the drug maker, Abbott Pharmaceuticals, and the sofosbuvir study was funded by drug makers Pharmasset and Gilead Sciences.

More than 3 million Americans have hepatitis C, a contagious liver disease usually spread through contact with the blood of someone already infected, according to the U.S. Centers for Disease Control and Prevention. The infection can be either acute or chronic. Chronic hepatitis C can scar the liver and eventually lead to liver failure. Poordad said it's one of the most common reasons for a liver transplant.

The current treatment combines two medications: interferon and ribavirin. Interferon is only available by injection, and must be administered three times a week for 48 weeks. Ribavirin is a pill. Side effects of interferon, which can last the duration of treatment, include flu-like symptoms, such as fever, chills, muscle aches and headache.

Poordad explained that this is because interferon dampens the whole immune system to keep the virus at bay. The new medications are what's called targeted therapies, which specifically go after the hepatitis C virus instead of attacking the whole immune system, he said.

"We're giving a drug that's killing the virus without bothering the host (the person with hepatitis C)," said Poordad.

His study had 50 people with genotype 1 hepatitis C, the most common and hardest-to-treat form of hepatitis C, according to Poordad. None had developed liver scarring (cirrhosis) yet.

Study volunteers were split into three groups. One group had never been treated for hepatitis C and received ABT-333, ribavirin and 250 milligrams (mg) of ABT-450 with 100 mg of ritonavir (making the ABT-450/r combination). The second group had also never received treatment. They received the same medications, except their dose of ABT-450 was 150 mg. The third group had received treatment for hepatitis C but had had no response or only a partial response to treatment. They were given ABT-333, ribavirin and 150 mg of ABT-450 and 100 mg of ritonavir.

The first two groups had a 95 percent and 93 percent sustained response to the drug. In the third group, only 47 percent had a sustained virologic response, the investigators found.
The most common side effects included abnormal liver function tests, fatigue, nausea, itching and headache.

The second study, conducted in New Zealand, included 95 people with hepatitis C genotypes 1, 2 or 3. They were split into eight groups and received varying treatments. All of the treatments included 400 mg of the new drug sofosbuvir.

Sustained response rates were impressive -- 100 percent -- when sofosbuvir was combined with ribavirin, or with interferon for people with genotypes 2 and 3. When sofosbuvir was given alone, it achieved a sustained response rate of 60 percent for those with genotypes 2 and 3.

For those with genotype 1 who had never received treatment, sofosbuvir and ribavirin achieved an 84 percent sustained response. For those who hadn't responded to prior treatment, this combination resulted in just a 10 percent sustained viral response rate.

Like ABT-450/r, the side effects for sofosbuvir included headache, fatigue, nausea and skin rash.
Experts welcomed the findings.

"Overall, these results are encouraging, and there's definitely a need for new treatments," said liver specialist Dr. Natasha Von Roenn, from Loyola University Medical Center in Chicago.
"Headache seemed to be a significant side effect in both studies, but the good news was that none of the patients had to stop treatment because of side effects," she noted.
"We're moving closer to having an oral interferon-free regimen with good response rates," she added.
Both studies were phase 2 studies, so neither treatment is yet available.

More information
Learn more about hepatitis C and its treatment from the U.S. Centers for Disease Control and Prevention.

Interferon-Free Therapies for Hep C Virus Look Promising
Sofosbuvir plus ribavirin and ABT-450/ritonavir, ABT-333, ribavirin combos seem effective
WEDNESDAY, Jan 2 HealthDay News- For untreated patients with hepatitis C virus (HCV), treatment with an oral nucleotide inhibitor of HCV polymerase, sofosbuvir, plus ribavirin seems effective for genotypes 1, 2, and 3; and the HCV NS3 protease inhibitor ABT-450, combined with low-dose ritonavir (ABT-450/r) plus the nonnucleoside NS5B polymerase inhibitor ABT-333 and ribavirin, seems effective for genotype 1, according to two studies published in the Jan. 2 issue of the New England Journal of Medicine.

Edward J. Gane, M.D., from Auckland City Hospital in New Zealand, and colleagues evaluated sofosbuvir in interferon-sparing and interferon-free regimens for patients with untreated HCV genotype 2 and 3. After 24 weeks of therapy, the researchers found that all patients who received sofosbuvir plus ribavirin without interferon or with interferon had a sustained virologic response. In addition, 84 percent of previously untreated patients with HCV genotype 1 had a sustained virologic response with sofosbuvir and ribavirin.

In a second study, Fred Poordad, M.D., from the University of Texas Health Science Center in San Antonio, and colleagues assessed the role of ABT-450/r, ABT-333, and ribavirin for treatment of HCV 1 infection without cirrhosis in a 12-week phase 2a study. The researchers found that most untreated patients had an extended rapid virologic response, and 93 to 95 percent had a sustained virologic response 12 weeks after the end of treatment. Forty-seven percent of those who had had a null or partial response to previous therapy with peginterferon and ribavirin had sustained virologic response 12 weeks after therapy.

"This preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and ribavirin may be effective for treatment of HCV genotype 1 infection," Poordad and colleagues conclude.

The Gane study was supported by Pharmasset and Gilead Sciences; the Poordad study was funded by Abbott.

Full Text - Gane (subscription or payment may be required)
Full Text - Poordad (subscription or payment may be required)

Wednesday, January 2, 2013

Dose-ranging trial indicated sofosbuvir (GS-7977) safe, effective in HCV genotype 1 patients

Healio›HepatologyChronic HepatitisNews

Dose-ranging trial indicated sofosbuvir safe, effective in HCV genotype 1 patients

Rodriguez-Torres M. J Hepatol. 2012;doi:10.1016/j.jhep.2012.11.018.

January 2, 2013

Patients with hepatitis C genotype 1 were more likely to experience rapid and sustained virologic response when treated with sofosbuvir in addition to pegylated interferon and ribavirin than peginterferon and ribavirin with placebo in a recent study.

In a double blind, multicenter, dose-ranging trial, researchers randomly assigned 64 adult, treatment-naive patients with chronic hepatitis C genotype 1 in a 1:1:1:1 ratio to receive peginterferon alfa-2a and ribavirin (PEG/RBV) with either placebo or 100 mg, 200 mg or 400 mg sofosbuvir once a day for 28 days, followed by PEG/RBV alone for 44 weeks.

After 28 days, patients in all three treated groups experienced a greater decline in HCV RNA than placebo recipients (mean change –5.3 log10 IU/mL in the 100-mg group; –5.1 log10 IU/mL in the 200-mg group and –5.3 log10 IU/mL in the 400-mg group). Treated patients had significantly higher rates of rapid virologic response, ranging from 88% to 94% across the three groups, compared with 21% in the placebo group. Rates of sustained virologic response (SVR)at 24 weeks also were higher among treated patients (56% for the 100-mg group, 83%, 200 mg; 80%, 400 mg vs. 43%, placebo).

No patients experienced virologic breakthrough during the 28-day period, but breakthrough occurred in four 100-mg group patients, and two each in the 400-mg and placebo groups during the 44-week period. Relapse occurred in five patients in the 100-mg group, three in the placebo group and one each in the 200-mg and 400-mg groups.

Adverse events occurred in 54 patients during the 28-day period. Nausea, fatigue, headache, chills and arthralgia were the most common events and were similar in frequency and intensity between all groups. Five patients discontinued treatment and five experienced serious adverse events during the 44-week period.

“The marked antiviral activity and SVR rates observed with 28 days of sofosbuvir in combination with PEG/RBV suggest that sofosbuvir may be a beneficial component of a treatment regimen for patients with HCV,” the researchers concluded. “Further studies are warranted to determine the optimal sofosbuvir treatment duration, efficacy of sofosbuvir in other genotypes of HCV infection (2 to 6), and whether sofosbuvir can play a role in interferon-sparing treatment regimens.”

Disclosure: See the study for a full list of relevant disclosures.

Tuesday, January 1, 2013

Paired CT Scans Catch Chemo-Killing of Liver Tumors in Real Time

Paired CT scans catch chemo-killing of liver tumors in real time

Immediate feedback shows if chemotherapy worked, or if additional treatment is needed

Using two successive pairs of specialized CT scans, a team of Johns Hopkins and Dutch radiologists has produced real-time images of liver tumors dying from direct injection of anticancer drugs into the tumors and their surrounding blood vessels. Within a minute, the images showed whether the targeted chemotherapy did or did not choke off the tumors' blood supply and saved patients a month of worry about whether the treatment, known as chemoembolization, was working or not, and whether repeat or more powerful treatments were needed.

CT scans of a liver tumor before and after chemoembolization.
Specialized DPCBCT scans of a liver tumor in a 73 year old man before and after chemoembolization (second and fourth column from left) match up closely with MRI scans taken over a month later (first and third columns).

The Johns Hopkins team's report about this novel use of dual-phase cone-bean computed tomography, or DPCBCT, an imaging technique developed at Johns Hopkins, is set to appear in the January 2013 edition of the journal Radiology. The diagnostic scans were performed on 27 men and women with inoperable liver cancer.

"This new scanning method is giving us almost instant feedback about the value of injecting antitumor drugs directly into large liver tumors and their surrounding blood vessels in an effort to quickly kill them, and to prevent the cancer from spreading," says senior study investigator and interventional radiologist Jean-Francois Geschwind, M.D.

Geschwind says if further testing proves equally successful, the paired use of cone-beam CT scans, which are already approved for single-scan use by the U.S. Food and Drug Administration, could supplant the current practice of MRI scanning a month after chemoembolization to check its effects.
"Patients should not have to endure the uncertainty of waiting weeks or more to find out if their chemoembolization was successful in fighting their liver cancer," says Geschwind, a professor in the Russell H. Morgan Department of Radiology at the Johns Hopkins University School of Medicine and its Kimmel Cancer Center.

"Dual-phase cone-beam CT avoids such delays, which also could allow the cancer to grow and spread and, ultimately, compromise chances of remission," he says.

Avoiding delays is particularly important, he says, for people with moderate to advanced stages of the disease, when liver tumors are too large or too numerous to surgically remove, and for whom chemoembolization is the main treatment option. Half of such liver cancer patients succumb within nine months, and liver transplantation is only an option for a quarter of those whose tumors have not spread outside the liver.

The newer DPCBCT scans, in which X-rays are detected by a device the size of a large laptop that can be placed directly below or above the operating room table, have the added advantage of being performed in the same room, or interventional radiology suite, as patients getting chemoembolization.

In their new study, Geschwind and his colleagues found that the initial shrinkage seen with DPCBCT scans taken before and after chemoembolization matched up almost perfectly with MRI scans taken a month later. Tumor death was 95 percent, the same as that seen by MRI. A total of 47 tumors were closely monitored in the study to assess how well DPCBCT tracked tumor death after chemoembolization.  All study participants were treated at The Johns Hopkins Hospital between March and December 2009.

In DPCBCT scanning, a chemical contrast dye is injected into the artery that supplies blood flow to the liver and tumor right before the chemotherapy drug is injected, to enhance the X-ray image. The first set of scans highlights key blood vessels feeding the tumor, as dye flows in and out of the tumor. The second set of scans is performed immediately after chemoembolization, to gauge tumor and key blood vessel death. Computer software is used to sharpen and analyze differences between the images.

The entire DPCBCT scanning time, researchers say, is between 20 seconds and 30 seconds, and the total amount of radiation exposure from the dual scanning averages 3.08 milliseiverts, which is less than half the amount of radiation involved in a modern abdominal 64-CT scan. Cone-beam CT scanners also emit an X-ray, but unlike other CT scanners, the cone-beam type of X-ray is projected onto one large, rectangular detector, roughly a foot and a half long -- and produces a telltale conical shape. The size of the cone-beam CT detector allows for single scans that can capture images the size of most people's entire liver. More powerful 64-CT and 320-CT scanners involve multiple detector rows.

Chemoembolization entails the use of tiny beads containing the chemotherapy drug doxorubicin injected directly into liver tumors.  Ultrathin catheters, about the width of a human hair, are threaded through blood vessels to deliver the drugs, which seep from the beads for several weeks.

Geschwind is leading clinical trials under way at Johns Hopkins and other centers to assess whether the combination drug treatment works for liver cancer patients. Early results have shown promise, with patients with advanced disease living 10 months to 15 months longer.

Geschwind says they plan improvements in image quality in DPCBCT scans, hoping further refinements will encourage physicians to adopt the technique. They also plan updates to the navigational software that, like GPS, can track blood vessels feeding each tumor, and provide more precise and greater numbers of targets.
Liver cancer kills nearly 20,000 Americans each year, and is much more prevalent outside the United States, where it is among the top three causes of cancer death in the world. Experts cite the rising numbers of hepatitis C infections, which cause chronic liver inflammation and are a leading risk factor for liver cancer.

Funding support for this study was provided by the French Society of Radiology and Philips Research North America in Briarcliff Manor, N.Y. Philips, whose parent company is based in the Netherlands, manufactures the CBCT device used in the study. Additional funding support was provided by the U.S. National Cancer Institute, a member of the National Institutes of Health. The corresponding grant numbers are NCI R01-CA160771 and UL1 RR-025005.

The study lead investigators were Romaric Loffroy, M.D., a radiology fellow at Johns Hopkins, and MingDe Lin, Ph.D., a Philips biomedical engineer based at Johns Hopkins who has been collaborating with Geschwind for the past five years to perfect the DPCBCT technique.
In addition to Geschwind, Loffroy and Lin, other Johns Hopkins researchers involved in this research were Gayane Yenokyan, Ph.D., at the university's Bloomberg School of Public Health; and Pramod Rao, M.D.; Nikhil Bhagat, M.D.; and Eleni Liapi, M.D., all at the School of Medicine. Philips investigators involved were Niels Noordhoek, Ph.D.; Alessandro Radaelli, Ph.D.; and Jarl Blijd, M.Sc.

The chemoembolization research study was funded by Bayer HealthCare and Onyx Pharmaceuticals, manufacturer of sorafenib, and Biocompatibles, makers of the microbeads. Geschwind is a consultant to Bayer HealthCare Pharmaceuticals, and to Biocompatibles. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

Photos of DPCBCT scans can be found online at:

For additional information, go to:

Triple therapy with boceprevir improved SVR among HCV patients with fibrosis, cirrhosis

Bruno S. J Hepatol. 2012;doi:10.1016/j.hep.2012.11.020.

 December 31, 2012

A regimen of boceprevir combined with pegylated interferon-ribavirin improved sustained virologic response in patients with hepatitis C and advanced fibrosis and cirrhosis, according to recent study results.

Using two phase 3, randomized double blind studies, researchers assessed the efficacy and safety of triple therapy — boceprevir (BOC) and peginterferon-ribavirin (PR) — among 178 treatment naive or unresponsive patients with HCV genotype 1 and advanced F3/F4 Metavir fibrosis scores. Patients assigned to three study arms received a 4-week lead-in of PR and then either 44 more weeks of PR plus placebo (PR48), PR in addition to BOC response-guided therapy (BOC/RGT), or PR plus BOC for 44 weeks (BOC/PR48).

Primary endpoint was sustained virologic response (SVR), defined as undetectable HCV-RNA levels, at week 24 of follow-up. Researchers found that HCV-RNA levels at weeks 4 and 8 were highly predictive of response, and no patients among the PR48 cohort with less than 1 log10 decline in HCV-RNA at week 4 achieved SVR. Conversely, patients in the BOC/RGT and BOC/PR48 arms reached SVR rates between 11% and 33% (for F3) and 10% and 14% (F4) when combining studies.

For (F3/F4) patients with a 1 or greater log10 decline at week 4, SVR rates for the BOC/PR48 arm were 77% and 87% in the two studies compared with 50% and 18% for PR48 patients. Fatigue and anemia were the most common adverse events in BOC/PR48 patients; neutropenia and thrombocytopenia were more common among cirrhotic patients than noncirrhotics.

“The results of these subgroup analyses suggest that BOC improves SVR rate in patients with advanced fibrosis/cirrhosis and that the longer treatment duration (4 weeks of PR plus 44 weeks of BOC plus PR) provides the greatest benefit to these patients,” the researchers concluded. “In this very difficult-to-treat subset of patients receiving triple therapy with BOC, the 4-week lead-in defines those in whom the addition of BOC results in low SVR rates.”

Disclosure: See the study for a full list of relevant disclosures.