June 15, 2013

In $15 billion hepatitis race, drugs move quickly from revolutionary to outdated

By Simeon Bennett, Published: June 13

GENEVA — Jean-Michel Pawlotsky has deja vu.

The doctor in the town of Creteil, just outside Paris, is telling hepatitis C patients to delay treatment until later this year, when two new drugs that may boost their chances of defeating the lethal liver infection hit the market.

It’s the same advice he offered two years ago, when earlier medicines developed by Vertex Pharmaceuticals and Merck & Co. were poised for approval. Now he says those drugs, hailed as breakthroughs in 2011, will soon be superseded by products from Gilead Sciences and Johnson & Johnson.

The pace of innovation, spurred by drugmakers jostling for a slice of a market that may reach $15 billion by 2018, has turned hepatitis C research into one of the fastest-developing areas of medicine. That boosted Gilead’s shares to a record last month, and left others like Vertex facing dwindling sales as their products quickly go from revolutionary to outdated.

“Things are moving very fast,” Pawlotsky, who teaches medicine at the University of Paris-Est, said by phone. “People are frustrated; they want more, better.”

Hepatitis C, an infectious disease that can scar the liver and afflicts about 170 million people worldwide, is still treated largely with injections that can take six months to clear the virus, sometimes don’t work and cause side effects ranging from flulike symptoms to depression. If untreated for longer periods, hepatitis C can cause cancer.

The current market

Gilead, a newcomer to the field, in April applied for regulatory clearance of a drug known as sofosbuvir. The pill may become the Foster City, Calif.-based company’s top-selling product by 2015 and reach sales of $6.3 billion by 2016, according to the average of nine analyst estimates compiled by Bloomberg. The stock has more than doubled in the past year on optimism about the pill.

Until 2011, there was only one standard treatment: the generic antiviral ribavirin, together with a weekly injection called pegylated interferon, sold by Roche Holding and Merck.

Two years ago, doctors and patients embraced the new drugs from Vertex and Merck because they boosted cure rates to about 80 percent from 50 percent. But they came with more side effects, including skin rashes and the risk of birth defects.

In clinical studies, newer formulations from Gilead and Johnson & Johnson show similar or better results in ridding patients of the disease, and fewer risks. Both may win regulatory approval this year. Johnson & Johnson’s Janssen unit applied in March for clearance of its product, simeprevir, which was developed by Medivir AB. Other drugs from AbbVie and Bristol-Myers Squibb are in late-stage trials.

“It’s not often you’re in a field that moves so fast and offers so much promise,” said Graham Cooke, a clinician at Imperial College London. “We’ve had very difficult treatments for so long, and we’re now in this era of incredible throughput from the pipeline.”

Vertex, of Cambridge, Mass., gets 76 percent of its revenue from Incivek, the hepatitis drug it developed with Janssen, which markets the treatment as Incivo in Europe. The drug won U.S. regulatory approval in May 2011, and prescriptions and sales reached a peak in the fourth quarter of that year but have declined since. The drug may garner sales of only $669 million this year, the average of 12 analyst estimates compiled by Bloomberg.

“We recognize that fewer patients are starting treatment for hepatitis C, however there are still patients who want or need to be treated now,” Erin Emlock, a spokeswoman for Vertex, said by e-mail. “Three of four people who start treatment today get Incivek, a number that’s unchanged since launch.”

To stoke demand, Incivo’s booth at a meeting of the European Association for the Study of the Liver in Amsterdam in April featured a video with the message, “Treat now to take your patient’s life off hold.”

Some doctors agree. The practice of delaying treatment to wait for better drugs, known as warehousing, is “irrational and almost unethical,” said Mitchell Shiffman, a clinician who sees about 1,000 new hepatitis C patients a year at the Liver Institute of Virginia. “If a patient can be cured now, why do you want to tell them to wait?”

French doctor Pawlotsky says people with mild disease aren’t harmed by a short delay. Most of his patients want to try the new drugs by participating in clinical trials, he says.

“Obviously, if we thought that the new treatments would come in something like five or six years, we would not warehouse,” he said. “But it’s a matter of months.”

More upcoming options

Mark Thursz, the secretary general of the European Association for the Study of the Liver, says many people he has put on experimental drugs are faring better than those using treatments now on the market.

“Our patients are struggling with the current regimes,” Thursz said. “The sooner we can get the new drugs licensed and in the clinic for our patients, the better.”

Gilead may charge up to $100,000 per patient for a course of sofosbuvir, according to ISI Group in New York. The drugmaker says it doesn’t comment on drug prices before they’re approved, but says the medicine can shorten treatment times to as little as 12 weeks, from as long as a year now.

Even as doctors disagree on whether to delay treatment, they have one eye on the next wave of drugs. At least three are in the final stage of clinical trials and may become available within two years.

Gilead is testing a combination of sofosbuvir with an experimental drug called ledipasvir in a cocktail that cured 100 percent of patients in a mid-stage trial presented in Amsterdam in April. AbbVie’s three-in-one combo won designation as a “breakthrough therapy” from the U.S. Food and Drug Administration on May 6, meaning it may be reviewed more quickly, after a study showed it cured 96 percent of patients after 24 weeks. Bristol-Myers Squibb’s three-in-one experimental combo won the same accelerated status just weeks earlier.

That means yet more difficult decisions about whether to treat or wait, said Dominique Larrey, a doctor at Saint-Eloi Hospital in Montpellier, France.

“I tell my students it’s like we’re in a therapeutic jacuzzi,” he said. “Each bubble is a new drug.”

— Bloomberg News


Hepatitis A: What You Should Know


Hepatitis A Virus

Provided by Food Poisoning Bulletin

June 15, 2013 by Linda Larsen

The Costco-Townsend Farms Hepatitis A outbreak has sickened at least 97 people in the southwest United States and Hawaii. Hundreds of thousands of bags of the frozen berry and pomegranate mix have been recalled, and many people have had to get a vaccination to prevent acute Hepatitis after eating or handling the product. So what is Hepatitis A?

There are seven types of Hepatitis, all identified by a letter. Hepatitis A is found in the feces of infected people. It is spread by eating or drinking food contaminated with the virus, by international travel and by close personal contact. Hepatitis B and C are found in blood and bodily fluids and aren’t transmitted by food or drink. You can be vaccinated against Hepatitis A and B; the CDC recommends that children should be vaccinated against Hepatitis A at one year, and infants, children, and teens ages 0-18 years should be vaccinated against Hepatitis B. There is no vaccine for Hepatitis C. Hepatitis A vaccinations protect for about 14-20 years in children and at least 25 years in adults.

Hepatitis D can only replicate in the presence of Hepatitis B virus; it is rare in developed countries. Hepatitis E is common in developing countries and is spread through fecal contamination; improving sanitation is an important measure of prevention. Hepatitis F and G, along with TT viruses are less common.

Hepatitis A incidence has declined precipitously in the United States since the vaccine was introduced in 1995. There were about 130,000 estimated cases in the U.S. that year. In 2010, the most recent year for which statistics are available, the estimated number of new infections was 17,000. The multiplier for infections is about 10, meaning that only 10% of cases are reported to public health officials.

You can be vaccinated after exposure to Hepatitis A within 14 days. The Hepatitis A vaccine is given to healthy people between 12 months of age and 40 years. Immune globulin is given to people aged 41 to 59 years, anyone over the age of 60, and persons under the age of 12 months. Anyone with chronic liver disease is given the immune globulin vaccination.

After 14 days, all you can do is monitor yourself for Hepatitis A symptoms, which include yellowing of the eyes and skin, dark urine, clay-colored stools, tiredness, and fever, nausea, and diarrhea. Some people lose their appetite and suffer abdominal cramping. The symptoms usually only last one to two weeks, but some people can be sick for six months. When the virus affects the liver, patients often require hospitalization. Treatment is usually supportive care; your body should clear the virus on its own unless you have underlying health issues.


Antiretroviral Treatment IS Prevention

Medscape HIV/AIDS

Benjamin Young, MD, PhD

Jun 14, 2013

It is well established that antiretroviral treatment (ART) can prevent HIV/AIDS-related morbidity and mortality in HIV-infected individuals. Published in 2011, the landmark HPTN 052 study confirmed that ART (and an undetectable plasma viral load) can virtually eliminate the risk for transmission of HIV to sexual partners.[1] These and other advances in our understanding of how the use of ART can work to prevent new HIV infection are changing the lexicon of HIV medicine.

The notion of treatment as prevention (TasP) is now firmly established in language of World Health Organization and US Department of Health and Human Services treatment guidelines as components of counseling and testing of serodiscordant couples. Indeed, expansion of access to treatment and earlier initiation of treatment can even be viewed not only as a strategy to reduce the burden of HIV disease, but also as a way to reduce new HIV infections in some resource-limited settings,[2] although much additional research and debate is needed to ascertain the feasibility and challenges of scaling up this approach worldwide at the level of communities or nations.

Giving medications to HIV-uninfected individuals to reduce risk for infection dates to the earliest days of ART, when postexposure prophylaxis strategies were introduced. Several recent reports, including the iPrEx study,[3] demonstrated the feasibility of preexposure prophylaxis (PrEP), or the use of ART to prevent HIV infection before exposure in at-risk individuals. Together, these data led to approval by the US Food and Drug Administration of oral tenofovir/emtricitabine for PrEP and the release of interim guidance on PrEP by the Centers for Disease Control and Prevention.[4]

However, enthusiasm for PrEP has been tempered by appreciation of the critical role of adherence to PrEP. Two large studies -- FEM-PrEP and VOICE -- were halted early because of lack of efficacy, at least in part driven by suboptimal adherence to medication.[5] Many other investigations continue into strategies to address these limitations, such as alternative dosing strategies and newer medications with long half-lives.

Appreciating the rapid pace of investigations into these issues, in 2012 the International Association of Providers of AIDS Care (IAPAC) convened an international summit in London to review the scientific literature and to bring together global thought leaders for the purpose of generating discussion and clarifying areas of consensus and controversy.

The Consensus Statement of the summit, published in the current issue of the Journal of the International Association of Providers of AIDS Care, summarizes of the state of the science from the perspective of a diverse panel of experts representing healthcare providers, researchers, policy-makers, pharmaceutical companies, governmental and nongovernmental agencies, and advocacy groups.[6]

The advisory committee concluded that the current evidence for TasP's effectiveness justifies ART use in persons who wish to start treatment early. However, the committee noted that additional research is needed to evaluate the effectiveness and cost-effectiveness of TasP, particularly at the national level, and that effective deployment of TasP requires efforts to scale up HIV testing and improving the cascade of engagement in HIV care.

In addition, the advisory committee acknowledged the considerable challenges for the implementation of successful PrEP programs, including financial constraints, the need to identify and reach at-risk populations, and the importance of training a cadre of healthcare providers in this new discipline. Nevertheless, the committee agreed that the current evidence on the effectiveness and safety of daily oral PrEP supports its use in high-risk groups. The committee also recommended that PrEP be part of a comprehensive risk-reduction package and that safety monitoring and adherence counseling are required.

In short, antiretroviral treatment is prevention. For persons already infected with HIV, ART prevents disease progression and death; for those recently exposed to HIV and for those at risk for HIV infection, postexposure prophylaxis and PrEP can prevent the establishment of infection. At its best, ART can reduce the burden of the HIV/AIDS epidemic and perhaps portend the beginning of an AIDS-free generation. There will be tremendous additional challenges in finding the political will to accomplish this goal and in defining an optimal way forward.

I look forward to seeing how much further the community has traveled down this pathway when we reconvene at the second International Summit on Controlling the HIV Epidemic with Antiretrovirals, in London, in September 2013.



CDC Launches First National HBV Testing Campaign for Asian-Americans and Pacific Islanders

Provided by Infection Control Today

Posted Yesterday

The Centers for Disease Control and Prevention (CDC) has launched Know Hepatitis B, the first national multi-lingual, multi-year communications campaign to increase testing for hepatitis B among Asian-Americans and Pacific Islanders. Though this group makes up less than 5 percent of the U.S. population, they account for more than half of the 1.2 million Americans estimated to be living with hepatitis B.

The campaign aims to reach millions of Asian-Americans and Pacific Islanders, particularly those that need information in their languages. The campaign is a partnership between CDC and Hep B United, a nationwide coalition of community organizations working to increase hepatitis B awareness and testing.

“If you or your parents were born in Asia or the Pacific Islands, it is critical that you get tested for hepatitis B,” says Howard Koh, MD, assistant secretary for health at the U.S. Department of Health and Human Services. “Everyone in the Asian-American community – from individuals, to community leaders, to physicians – can all help us put an end to this epidemic by getting tested and talking about hepatitis B.”

In the U.S., Asian-Americans and Pacific Islanders are one of the groups hardest hit by hepatitis B, which can cause potentially fatal liver damage, including liver cancer. Hepatitis B-related liver cancer is a leading cause of death among many in these communities. Hepatitis B is especially common in many Asian and Pacific Island countries, and many with chronic hepatitis B became infected as infants or young children. It is usually spread when someone comes into contact with blood from someone who has the virus.

It is estimated that 1 in 12 Asian-Americans and Pacific Islanders is living with hepatitis B. Yet, as many as 2 in 3 living with the virus do not know they are infected, because the disease often has no symptoms until serious liver damage has already occurred. Testing allows those with hepatitis B to take steps to protect their health, including starting treatment that can delay or reverse the effects of liver disease.

“Hepatitis B is one of the most severe health disparities facing Asian Americans and Pacific Islanders,” says John Ward, MD, director of CDC’s Division of Viral Hepatitis. “With greater awareness and testing, we can save lives and decrease the burden of hepatitis B in Asian American communities and throughout the United States.”

Know Hepatitis B is designed to resonate with those most affected by hepatitis B, and was developed with input from Asian Americans and Pacific Islanders from around the country. It will deliver culturally relevant messages in multiple languages, including English, Chinese, Korean and Vietnamese, through a wide range of channels, including:

- Online and print ads and public service announcements in media outlets serving Asian American and Pacific Islander communities

- Social media and digital materials to encourage testing

- Outreach led by Hep B United and its local partners to mobilize communities to get tested

- Outreach to health professionals to educate them on the importance of hepatitis B testing for Asian Americans and Pacific Islanders

Many of the campaign’s messages build on the strong family ties relevant to many Asian-American and Pacific Islander cultures. For example, one ad features a father and his young daughter with the tagline, “I’m an invincible Dad, a thoughtful husband. I get tested for hepatitis B.” Another encourages U.S.-born Asian Americans and Pacific Islanders to talk to their parents about getting tested.