T.G.I.F Hepatitis News Ticker; Hep C Drugs:Bristol-Myers, Merck and Vertex

New On The Blog

AASLD- Abstracts To Be Presented At The Nov Meeting;
AASLD-Vertex presentation of New Data; INCIVEK™and VX-222
AASLD-New Data On BMS-790052 and BMS-650032 to be presented by Bristol-Myers Squibb
AASLD-Acceptance of Four TMC435 Abstracts by Medivir
AASLD-New Data Analyses for VICTRELIS™ (boceprevir) will be Presented By Merck

Hepatitis C patients likely to falter in adherence to treatment regimen over time
Galectin-inhibiting therapeutics to treat fibrosis, liver disease and cancer
Consider Hepatitis C Infection in Some Arthritis Patients
Liver Health and Wellness

Four Ways to Beat Hepatitis Fatigue
Fatigue is a problem frequently experienced by those with chronic hepatitis. Fortunately, there are several different kinds of approaches that can help mitigate fatigue.
by Nicole Cutler, L.Ac.
As the most common symptom of chronic hepatitis, fatigue is also one of the hardest ones to address. Likely because of the complex combination of cellular and chemical processes involved in producing energy, battling fatigue is best accomplished through a variety of different approaches....

Local towns among hot spots for high rates of HIV, Hep C
NEW GLASGOW – Local groups are claiming that the incidence of AIDS, HIV and Hepatitis C is increasing rapidly in Pictou County, primarily due to a rising number of intravenous drug users in the region.

Rayann Toner, executive director of the Pictou County Centre for Sexual Health, says that a study done by Caroline Ploems for Health Canada Population and Public Health Branch shows that there are six “hot spots” in mainland Nova Scotia where injection drug use has been identified as a problem.

FYI-Pharmaceuticals

The Next Big Thing In Biotech: Hep C Drugs

Adam Feuerstein, senior columnist for TheStreet, explains why hepatitis C
drugmakers will be the biotech stocks to watch in the coming week.

ANALYSIS-Vertex takes early rounds of hep C bout with Merck

29 Sep 2011 17:48 Source: reuters // Reuters

New prescriptions for Vertex drug outpacing Merck entry

* Incivek could be one of fastest drugs to reach $1 bln

* VA contract could give boost to Merck

By Bill Berkrot
Sept 29 (Reuters) - In the bout between a pair of breakthrough hepatitis C treatments, Incivek from upstart biotech Vertex Pharmaceuticals appears to have taken the first round from pharmaceutical heavyweight Merck & Co and its Victrelis by a wide margin.

The companies next month will report sales from the first full quarter on the U.S. market for their new medicines, and weekly prescription data indicates that Merck has some serious catching up to do.

About 1,100 new patients are likely to begin Incivek treatment each week in the fourth quarter compared with about 300 new patients for Victrelis, according to Wolters Kluwer, a provider of analytical data to the healthcare industry.

It estimates U.S. Incivek sales reaching $752 million in 2011 -- a trajectory that would see the drug surpass $1 billion in its first year on the market -- making for one of the most successful drug launches in history.

Genentech's blockbuster cancer drug Avastin, which was approved in February 2004, racked up its first billion dollars in sales in about a year and a half.

In contrast, Wolters Kluwer inThought unit is forecasting $146 million in 2011 U.S. Victrelis sales.

"It's absolutely impressive," Julie Hoggatt, an analyst for inThought, said of Incivek performance out of the gate. "It does seem that Vertex, being that this was its first launch, did a very good job."

The two drugs, which promise far higher cure rates for the serious liver disease than prior standard treatments, as well as the potential for shorter treatment durations, were approved within days of each other in May.

Analysts said that Merck has made some savvy moves, including a co-promotion deal with rival Roche - the biggest seller of one of the older drugs that must be used in combination with the new medicines.

But it has so far been unable to alter the perception that Vertex has the better drug, even though the two have never been tested against each other.

In the final round of clinical trials Incivek, known chemically as telaprevir, cured between 75 percent and 80 percent of patients. Victrelis, known chemically as boceprevir, cured 66 percent. Both results easily topped the cure rate of only about 40 percent for the previous standard treatments that had to be taken for nearly a year and which often caused miserable flu-like symptoms.

SIMPLICITY, POTENCY

While many industry observers believed the Roche co-promotion would help bring the market share split much closer to 50-50, Incivek has so far been dominating.

"There was a feeling that maybe Merck could do a little bit better because they've done some unique things in the marketplace," said Deutsche Bank analyst Barbara Ryan.

"The reality is that the Vertex drug is more potent, has a more straightforward, simple dosing regimen, and for that reason they got the lion share of the market," she added.

"We still think that in some markets, like the Asian markets, that Merck will do better than its share here just because the company's presence in those markets is so strong," Ryan said.

Both drugs were recently approved in Europe, where Johnson & Johnson will sell the Vertex drug.

Hoggatt agreed that simplicity and a larger percentage of patients who qualify for shorter treatment time with Incivek were working in Vertex favor.

"One negative for boceprevir is how confusing its label is," Hoggatt said. "I think maybe seeing some hesitation from physicians because of the complexity."

Under the Victrelis regimen the two older drugs -- interferon and ribavirin -- are taken for four weeks before the Merck drug is added to the mix. There are several treatment duration variables depending on a patient response to the drugs at certain points along the way.

With Incivek, all three drugs are taken from the beginning and there are fewer pills and fewer duration variables.

"Patients are asking for telaprevir," confirmed Dr. Douglas Dieterich, a liver disease specialist and professor of medicine at Mt. Sinai School of Medicine in New York.

"It's probably going to become less telaprevir-dominated as the side effects roll in," Dieterich predicted. Incivek has been associated with serious rash in clinical trials.

But asked if patients have also been asking for the new Merck drug, Dieterich said, "No. Not at all."

Both companies have so far limited consumer marketing to campaigns aimed at raising awareness of hepatitis C, a disease that someone can have for many years without symptoms. If untreated, it can lead to cirrhosis, liver cancer and death.

"While it's still early, we are off to a good start with the launch of Victrelis and are encouraged by the positive responses we received on our product from physicians, patients and payers," Merck spokeswoman Pamela Eisele said.

Merck has won a contract for Victrelis to be the preferred treatment option by the U.S. Department of Veterans Affairs that serves thousands of patients, which should provide a boost for its drug.

But Merck may need to alter course and begin to promote its brand with consumers to get patients to start asking doctors for Victrelis if it is to close the gap.

"We thought it would be little better on the Merck side as a percent, less than 50 but certainly better than 25 percent," said Barclays Capital analyst Tony Butler.

But Butler said it was too early to declare a winner.

"In the past I've been surprised at how things have changed over time," he said. (Reporting by Bill Berkrot in New York, editing by Matthew Lewis)

Bristol-Myers Is Close To Completing A Groundbreaking Hepatitis C Treatment (BMY)
AP) — The drugmaker Bristol-Myers Squibb Co. is building a hepatitis C virus treatment franchise that could be launched by 2015 and produce as much as $2.9 billion in global sales five years later, according to a Citi analyst.

The New York company is close to starting a late-stage clinical development program for the franchise in Japan, where its opportunity is underappreciated, Citi analyst John T. Boris said in a research note late Thursday. He said it is estimated that there are as many as 2 million hepatitis C virus carriers in Japan, with 20 percent diagnosed and 30 percent treated.

Another late-stage trial was started this month and is expected to be completed in 2013

Hepatitis C is the primary cause of liver transplants in the United States and is expected to become a much larger public health problem as aging baby boomers succumb to the disease. It’s an infectious disease that can be spread by sharing needles or having sex with an infected person.

Boris said in the note he is maintaining a “buy” rating on Bristol-Myers shares, which have risen more than 17 percent in value so far this year.

The stock closed at $31.12 on Thursday after hitting a 52-week high of $31.78 earlier this month.

Combined Effects of HBV, HCV on Hepatoma Vary With Age, Gender
By Dave Levitan NEW YORK (Reuters Health)
Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is associated with substantially higher risk of hepatocellular carcinoma than single infections, but the complex interactions of the viruses vary depending on gender and age, a study from Taiwan shows. The researchers report that in general, coinfection produced weaker effects than previously reported.

"By the age of 75 years, one quarter of patients or more affected by chronic viral hepatitis will be affected by hepatocellular carcinoma," or HCC, the research team noted in an August 22nd online paper in the Journal of Clinical Oncology. Led by Dr. Yen-Tsung Huang of Harvard University, the study tracked 23,820 residents of Taiwan aged 30 to 65 years at enrollment in 1991-1992. Overall, 17.44% were seropositive for HBV surface antigen and 5.52% were seropositive for antibodies against HCV. Altogether, 477 subjects developed HCC. The cumulative lifetime incidence of HCC for was 38.35% for men with both viruses and 27.40% for women with both viruses. Men and women who were seropositive only for HBsAg had cumulative lifetime HCC rates of 27.38% and 7.99%, respectively.

These rates in men and women with only HCV were 23.73% and 16.71%, respectively. In contrast, the cumulative lifetime incidence rates for subjects with neither virus were 1.55% in men and 1.03% in women. On multivariate analysis, the hazard ratio for HCC was 19.5 for those positive for both infections. The interactive effects of the two viruses varied based on age, however. The HCC risk with dual infection was "sub-additive" before the age of 65 years, especially in men. But after age 65, the risk with dual infection was "consistently higher than that for single infection." Specifically, in older patients, the HR in men was 22.38 for dual infection vs. 8.94 and 12.34 for single infections with HBV and HCV, respectively. In women after age 65, HRs for HCC were 27.29 with dual infection, 6.58 with HBV and 15.01 with HCV. "With the increase in age, the HCC risk decreased in HBsAg-seropositive men but increased in anti-HCV-seropositive women," said study senior author Dr. Chien-Jen Chen, of the National Taiwan University in Taipei, in an email to Reuters Health.

The authors advise more intensive clinical management of patients with dual infection. "The therapy of chronic HBV/HCV infection using antivirals and/or interferon may reduce the risk of newly developed HCC," Dr. Chen said. "Frequent liver surveillance using various imaging methods (ultrasonography, CT scan, angiogram, etc.) may help early detection of small HCC, which may be treated more effectively and efficiently by surgery or embolization. The HCC case fatality may thus be lowered."
SOURCE: http://bit.ly/qydCw3

J Clin Oncol 2011. Analysis of the sustained virological response in patients with chronic hepatitis C and liver steatosis.
Piccoli LD, Mattos AA, Coral GP, Mattos AZ, Santos DE.
Abstract
CONTEXT:
Chronic hepatitis C as well as non-alcoholic fatty liver disease are recognized as the main cause of liver disease in Western countries. It is common to see the concomitance of the diseases and the influence of steatosis in the sustained virological response of patients with hepatitis C virus.
OBJECTIVE:
Assess the sustained virological response in chronic hepatitis C patients according to the presence of liver steatosis.
METHODS:
One hundred sixty patients with chronic hepatitis C were retrospectively evaluated. Demographic data such as gender, age, body mass index, presence of diabetes mellitus and systemic arterial hypertension, virus genotype and use of pegylated interferon were analyzed, as was the staging of fibrosis and the presence of steatosis at histology.
RESULTS:
Most patients were male (57.5%), with a mean age of 48 ± 9.7 years. The most frequent genotype observed was 3 (56.9%) and, in the histological evaluation, steatosis was observed in 65% of the patients (104/160). Sustained virological response in patients with steatosis occurred in 38.5%, and in 32.1% in patients without steatosis (P = 0.54). When we analyzed possible factors associated with the presence of steatosis, only body mass index and systemic arterial hypertension revealed a significant association. When the factors that influenced sustained virological response were evaluated in a logistic regression, genotype and use of pegylated interferon proved to be independent factors associated to the response.
CONCLUSION:
In the evaluated patients the presence of liver steatosis did not influence the sustained virological response of patients with chronic hepatitis C treated with interferon and ribavirin.
PMID:
21952702
[PubMed - as supplied by publisher]

HIV

From NATAP
ICAAC: ICAAC 2011: Medically Important Highlights - David H Shepp, MD, Hofstra NSLIJ Medical School Division of Infectious Diseases North Shore University Hospital - Manhasset-
Novel Treatments for HIV
Adoptive Transfer of CCR5-Modified T-cells. Combination antiretroviral therapy (ART) can suppress the growth of HIV and restore immunity to opportunistic illnesses. However, latent virus is not eliminated, requiring lifelong treatment to maintain benefit. An important thrust of current HIV research is directed to finding therapies that will allow ART to be discontinued. The apparent cure of HIV infection in a patient with leukemia who received allogeneic hematopoietic stem cell transplantation (HSCT) from a CCR5 delta 32 homozygous donor has triggered renewed interest in gene therapy for treatment of HIV

Liver Cancer

‘Micro’-chemo and Cancer Pill Combo Tested in Liver Cancer Patients
A combination of an oral drug, called sorafenib, and a method for injecting microbeads of chemotherapy directly into tumors has been proven safe for liver cancer patients and may improve outcomes for those who have these fast-growing, deadly tumors whose numbers are on the rise in the U.S.

Reporting in the Sept. 12 online version of the Journal of Clinical Oncology, Johns Hopkins investigators tested the combination in 35 patients with advanced, inoperable liver cancer. Both sorafenib and the chemotherapy drug used in this study, doxorubicin, have independently – but not in combination — been approved to treat liver cancer.

Combining the right therapies at the right time is an intense focus of study among cancer experts, and Johns Hopkins interventional radiologist Jean-Francois Geschwind, M.D., saw promise in the two therapies tested in the current study.“Both therapies have increased survival rates in advanced liver cancer, and combining them may push those survival rates further,” says Geschwind, professor of radiology, surgery and oncology at Johns Hopkins.

For the study, Geschwind employed a method called chemoembolization that uses catheters the size of a single hair to deliver microbeads filled with high concentrations of the chemotherapy drug, doxorubicin, directly to the tumor. The chemotherapy seeps out of the microbead for at least three weeks.

Sorafenib, approved for its ability to block a key pathway, depriving tumors of blood vessels, was given twice daily to patients one week before their chemoembolization procedure. “The idea is to block blood vessel formation in these cancers, which typically peaks 24 to 36 hours after chemoembolization. This may help prolong the chemotherapy’s impact.” says Geschwind.

Patients treated with the combination had no more side effects than reported for sorafenib or chemoembolization alone, according to Geschwind. Common side effects included fatigue, skin reactions in hands and feet, and body rash.

Patients in the study were admitted to the hospital overnight for their chemoembolization treatment. The patients continued oral sorafenib twice daily until their disease progressed. For the study, Geschwind says that patients received up to four chemoembolization treatments within a six-month period.Primary liver cancer incidence is rising in the U.S., says Geschwind, because of increasing rates of hepatitis C infections, which cause liver inflammation and are major risk factors for liver cancer.

Liver cancer tends to grow rapidly and without specific symptoms. Measures of a liver cancer marker called alpha-fetoprotein are elevated in only half of patients, adds Geschwind, making it difficult to find the disease early.

When the cancer is confined to the liver, doctors can transplant or remove the liver, but three-quarters of patients are not eligible for surgery. Without treatment, median survival of these inoperable patients is typically less than nine months. Chemoembolization procedures add 10 to 15 months of survival.

A phase III trial comparing chemoembolization with or without sorafenib is under way at Johns Hopkins and 100 other sites in the U.S. “We’re on the path to improving the standard of care for liver cancer,” says Geschwind.

The study was funded by Bayer Health-Care and Onyx Pharmaceuticals, manufacturer of sorafenib, and Biocompatibles, makers of the microbeads.

Researchers involved in the study include Timothy Pawlik, Diane Reyes, David Cosgrove, and Ihab Kamel, Nikhil Bhagat of Johns Hopkins.

Pawlik and Geschwind are consultants to Bayer HealthCare Pharmaceuticals, and Geschwind is a consultant to Biocompatibles. The terms of these arrangements are being managed by the Johns Hopkins University in accordance to its conflict-of-interest policies.

Liver Cancer Drug Provectus Receives Orphan Drug Designation From FDA
The U.S. Food and Drug Administration (FDA) has given orphan drug designation to Provectus Pharmaceuticals, Inc., for Rose Bengal, the active component in their new oncology medication PV-10. The drug is designed for the treatment of hepatocellular carcinoma (HCC), the most prevalent form of liver cancer. At present Provectus is designing a Phase II investigation, following the January 2011 completion of their Phase I study, which involved patient accrual and treatment of PV-10 for liver cancer in all participants...

Media

Listeriosis Deaths Climb to 13 in 'Deadliest' Outbreak
By Todd Neale, Senior Staff Writer, MedPage Today Published: September 28, 2011 The listeriosis outbreak stemming from tainted cantaloupes has sickened at least 72 individuals, killing 13 of them, according to the CDC. "This is the deadliest outbreak of a foodborne disease that we've identified in more than a decade," said CDC director Thomas Frieden, MD, MPH, on a conference call with reporters Wednesday. Overall, 18 states have been affected as of Monday, with four different strains of Listeria monocytogenes implicated. State and federal health officials are continuing to investigate other listeriosis cases across the country that might be related to the outbreak. Most of the infected individuals are older than 60 or have conditions that weaken the immune system, the CDC said in its most recent update. All but one of the patients with information on hospitalization have required admission.

The 13 confirmed deaths have occurred in New Mexico (four), Colorado and Texas (two each), and Kansas, Maryland, Missouri, Nebraska, and Oklahoma (one each). That figure is more than triple the four deaths reported last week. Early on in the investigation, the Colorado Department of Public Health and Environment identified cantaloupes grown in the Rocky Ford region of the state as the likely source of the outbreak, which is unusual because Listeria has not previously been seen in cantaloupe. Within days, the department pinpointed the exact source as whole cantaloupes grown at Jensen Farms' production fields in Granada, Colo., which was later confirmed by the FDA.

The FDA said it is working with other agencies to determine how the contamination of the facility occurred, with consideration given to all environmental factors on the farm, including possible animal intrusions, water quality, and growing practices. On Sept. 14, Jensen Farms recalled its Rocky Ford brand whole cantaloupes, reporting distribution to 17 states. In its update, the CDC said that the cantaloupes were shipped to at least 25 states, with the possibility of further distribution. Even though the cantaloupes have been recalled, the CDC said that it expects to receive reports of more cases related to the outbreak through October because individuals can develop listeriosis up to two months after coming into contact with the bacteria. The shelf life of cantaloupe is about two weeks, and all of the affected product was shipped from July 29 to Sept. 10.

The FDA said that it is collaborating with state health officials to check retail stores, wholesalers, and distributors to make sure they know about the recall and that they have taken steps to inform customers and remove affected product from shelves. The agency said that consumers should throw away any of the recalled cantaloupes from Jensen Farms and should not try to wash the bacteria off of the fruit. The CDC recommended that people at high risk for listeriosis -- including older adults, immunocompromised individuals, and pregnant women -- should not eat Rocky Ford cantaloupes from Jensen Farms, and that other individuals should not eat those cantaloupes if they want to reduce their risk of Listeria infection. The agency noted that the bacteria can grow both at room temperature and in the refrigerator.
"For the public, it's important to know that if you know the cantaloupe that you have is not [from] Jensen Farms, then it's okay to eat," Frieden said, "but if you're in doubt, then throw it out." According to the CDC, there are about 800 reported cases of Listeria infection each year in the U.S., with three or four outbreaks. Typical sources include deli meats, hot dogs, and Mexican-style soft cheeses made with unpasteurized milk, although produce -- including sprouts in 2009 and celery in 2010 -- has been implicated as well.

Frieden said over the past decade there have been about 10 outbreaks of foodborne illness in which cantaloupes were the definite vehicle for infection, seven involving Salmonella and three involving norovirus. He added that the number of multistate outbreaks of foodborne illness in general have increased substantially in recent years. "This is a reflection at least of better quality monitoring and perhaps also of the increasing complexity and centralization of the food supply," he said. "It's not that food is getting riskier, but we're getting better at identifying problems that have probably been there for a long, long time."
FDA commissioner Margaret Hamburg, MD, added that "these kinds of outbreaks are a powerful reminder that, despite the fact that we have one of the safest food supplies in the world, it does remain vulnerable to contamination, and the American people remain vulnerable to foodborne illness."

Off The Cuff

September 29, 2011, 12:01 am
Why Doctors Order So Many Tests
By PAULINE W. CHEN, M.D.
One afternoon when I was running later than usual, I recognized a familiar face among the patients waiting to see me. A voluble newspaper fanatic, the gentleman, in his 70s, was usually eager to discuss the latest headlines with me. That day, however, he was remarkably quiet. He was suffering from the flu. “I’m really feeling no good,” he rasped.

Australia: Poor Hospital Supply Lines Endanger Patients

Julie Robotham (The Sydney Morning Herald, September 29, 2011) "Hospitals operate with less than a month's supply of many essential medicines, leaving patients vulnerable if local distributors are unable to import them through fragile international supply chains. The issue was emphasized [recently when]…the sole supplier [revealed that it]…would be unable to import intravenous penicillin until December…Yvonne Allinson, the head of the Society of Hospital Pharmacists of Australia, said state and federal governments should co-operate to ensure viable supplies of essential drugs were maintained…Current purchasing policies discouraged companies from manufacturing in Australia, and incentives to encourage local research had been eroded. A spokeswoman for the Department of Health and Ageing said there were already 'well-developed processes to ensure an adequate supply of essential medicines in the Australian market,' but temporary shortages were not uncommon."

Medical marijuana as a treatment for cancer
FERNDALE -- When his cancer came back for a fifth time, Michael McShane was desperate for treatment outside of traditional medicine.
The last time squamous cell carcinoma left lumpy tumors around his mouth, doctors cut it away and reconstructed his bottom lip by turning out a portion of its inner layer.
In all, the state act defines 14 chronic or debilitating diseases, medical conditions, and side effects from treatments that qualify, including glaucoma, HIV/AIDS, hepatitis C, amyotrophic lateral sclerosis, Chrohn’s disease, agitation of Alzheimer’s disease, nail patella, Cachexia or wasting syndrome, and seizures.