April 5, 2012

Doubts arise on Idenix’s hepatitis drug


April 05, 2012

Idenix Pharmaceuticals Inc. sank the most in eight months as investors speculated the Cambridge company’s experimental hepatitis C treatment may face hurdles. The shares had tripled in the 12 months before Wednesday. Roche Holding reported an “unacceptable relapse rate’’ for patients on a combination of medicines that Brean Murray Carret & Co. analyst Brian Skorney called a “good surrogate for any oral combination that includes IDX184,’’ Idenix’s medicine. “We believe Idenix will need to explore regimens with durations of greater than 12 weeks to be effective,’’ Skorney wrote. “We believe this could significantly delay clinical development and makes IDX184 substantially less attractive.’’


Study Explains How the First Effective HIV Vaccine Worked


TS Photography / Getty Images

By Alice Park | @aliceparkny | April 5, 2012

In 2009, researchers reported that an AIDS vaccine had for the first time protected people against HIV. Since then, the researchers have been wondering, How did it work?

One of the biggest black boxes in AIDS research remains the important question of what actually protects the body from HIV. Is it antibodies to the virus? Or is it immune cells that are targeted to recognize and eliminate HIV?

AIDS researchers have only been able to guess at what these critical weapons against HIV could be, which is partly why their efforts to create a vaccine have thus far been marked by a long line of failed attempts. But when the RV144 trial in Thailand showed promise in 2009, scientists finally had something to work with. The vaccine was only modestly effective — protecting just 31% of heterosexual adults from infection — especially compared with inoculations against other common infectious agents like measles or mumps, which are 95% to 98% effective. But it was a start.

(MORE: AIDS Vaccine: The Promise of HIV Antibodies)

Studying blood samples from the original Thai trial, Dr. Barton Haynes, director of the Duke Human Vaccine Institute of Duke University, and his colleagues report this week in the New England Journal of Medicine that they have begun to understand how the vaccine worked. Two HIV-binding antibodies may play an important role in determining whether the virus can gain a foothold in healthy cells and start an infection, the researchers say.

The scientists began with blood samples from 246 trial participants who were vaccinated; 41 people later became infected with HIV and 205 did not. After a two-year search for the right antibodies or other factors that could be responsible for protection against HIV, they zeroed in on 17 assays that were “sensitive, specific and could pick up something this vaccine did to allow us to compare before and after,” says Haynes.

The researchers then focused on six of the strongest variables, and then compared those who got infected with those who did not. The groups differed in levels of two antibodies. One, called V1V2, is made by the immune system to bind to HIV’s outer coating; part of the immune cell family called IgG, this antibody may be critical in preventing the virus from attaching to and then gaining entry into a healthy cell. Those with higher levels of V1V2 antibodies were less likely to become infected with HIV than those with lower levels.

The other antibody, however, had the opposite effect. Part of the IgA family of immune cells, these antibodies, which bound to a different part of HIV, seemed to increase the risk of infection: higher levels of IgA binding to HIV were linked with higher rates of infection, which suggested that rather than protecting against the virus, the vaccine was actually helping HIV to do its pathogenic duty. “Our first thought was, Oh, my gosh, this vaccine is inducing antibodies that enhance infection,” says Haynes.

(VIDEO: Q&A With Bono on the Global Fight Against HIV/AIDS)

But that didn’t make sense, since the vaccine was 31% effective in warding off infection. When the researchers compared IgA levels among those who were vaccinated and became infected with those who didn’t get the vaccine, they found the two groups had similar infection rates. That provided some relief, since it suggested that the IgA antibodies were not enhancing infection. Rather, the antibodies appeared to be countering the effect of the V1V2 antibodies that were fending off HIV and undoing their protection.

That’s an important finding, since it hints at how complex any successful HIV vaccine must be in order to protect people from infection. Unlike viral infections such as influenza, measles and mumps, AIDS is caused by a much wilier virus that survives and replicates by inserts itself into its host’s genome and becoming a part of the cell. To be protected against such an intrusion, says Haynes, it may take an exquisite balance of both turning up defensive immune cells that target and destroy viruses, as well as turning down the body’s natural suppression systems that keep the immune system from overreacting — much like regulating a vehicles speed by using both the accelerator and the brakes.

That understanding could also clarify why previous vaccine candidates have failed. Some might have been successful in eliciting the proper antibodies or immune responses, but failed to provide an overall protective effect because they were washed out by the counteracting antibodies. “We have a direction now, with tools and clues to check out in previously completed trials, why they might have worked or might not have worked,” says Haynes.

(MORE: HIV Drugs May Prevent Infection in Healthy Individuals)

“This analysis has produced some intriguing hints about what types of human immune responses a preventive HIV vaccine may need to induce,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped fund the study, along with the U.S. Army Medical Research and Materiel Command and the Bill and Melinda Gates Foundation, in an statement. “With further exploration, this new knowledge may bring us a step closer to developing a broadly protective HIV vaccine.”

And because of the way HIV works, that vaccine needs to be able to protect people immediately and powerfully. “For this vaccine, we have got have all our antibodies and killer cells and armamentarium upfront,” says Haynes. “The person has to be completely protected from infection at the time they are challenged by HIV.”

And now, with the first clues about how to develop that protection, a more effective anti-HIV vaccine might actually be possible in coming years.

Alice Park is a writer at TIME. Find her on Twitter at @aliceparkny. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.


In hepatitis C: Curing the incurable

April 5, 2012

Although not nearly as well-known as AIDS, hepatitis C affects about 200 million people worldwide — about four times the number of HIV cases. In the U.S. alone, about 4 million people are infected. Hepatitis C, which is usually transmitted through contact with infected blood, causes a slow but progressive deterioration of liver function, leading to cirrhosis and sometimes liver cancer. There were no satisfactory therapies for the infection until last year, when Merck and Vertex each launched a protease inhibitor-type drug — an anti-viral analogous to those used successfully in taming HIV. When added to the existing standard therapies, the new drugs essentially doubled the cure rate. Yet one of the remaining problems with this treatment option is that it includes interferon, which is very difficult to tolerate due to its severe side effects, which include depression, nausea, and flu-like symptoms.

However, ACSH’s Dr. Josh Bloom predicted last year that the Holy Grail of hepatitis C therapy — curing the disease without the use of interferon — might be discovered by Abbott Laboratories. And a new study suggests that this now could be the case. According to recent research, hepatitis C patients who had never before received treatment and were given Abbott’s latest four-drug cocktail showed an astounding 95 percent cure rate. In more difficult cases, where patients had already tried and failed other therapies (and were generally regarded as untreatable), 47 percent were cured. Best of all, this novel drug combination does not include interferon — the first time this has been possible.

“This just goes to show that pharmaceutical critics, like Marcia Angell of the Harvard School of Public Health, who criticize so-called ‘me-too’ drugs as being non-innovative are displaying their ignorance about drug development,” says Dr. Bloom. “The second or third drug in a new class is often superior to the original. Such changes can add up to enormous medical advantages, despite what vocal critics wrongly maintain.”



What can I do for a fatty liver?

By Howard LeWine, M.D., Tribune Media Services The Medicine Cabinet

March 28, 2012

Q: A recent blood test revealed abnormally high liver enzymes. My doctor says I have fatty liver disease. I've started eating artichokes (after reading these were good for your liver), as well as cutting back on my food intake. I'm also eating lots of vegetables and beans, and plan to exercise more and drink less alcohol. Do you think these measures might help?

A: Yes, you're off to a great start

Having a fatty liver means that an excess of triglycerides (one type of fat) have accumulated inside liver cells. This condition is also known as steatosis. When the fat causes the liver to be inflamed, liver enzymes are released into the blood. Doctors call this steatohepatitis.

The primary causes of fatty liver are weight gain, overuse of alcohol, diabetes, and insulin resistance. Insulin resistance means that the body has become less responsive to rising blood sugar levels. To compensate, the pancreas has to make more insulin and send it into the blood stream. Higher blood levels of insulin slow down the normal turnover of triglycerides in liver cells, so they build up.

Most often, people with fatty livers don't have any symptoms. Like you, many people are diagnosed when a blood test shows elevated liver enzymes. Or a doctor detects an enlarged liver during a physical exam. Sometimes, a large fatty liver is seen on an ultrasound or CT scan of the abdomen when the test is ordered for some other reason.

Untreated steatohepatitis can progress to cirrhosis of the liver -- a serious condition where the liver becomes unable to do its job of cleaning toxins out of the bloodstream.

Eating healthier and decreasing alcohol use should help. But in my mind, it's not enough. I recommend complete abstinence from alcohol and cutting calories to lose weight.

Exercise is a must. You can start slow, but you do want to progress to a minimum of 30 minutes of dedicated aerobic exercise daily. An hour of moderate intensity exercise most days of the week would be best.

I'm not sure if eating artichokes will help. But they surely won't hurt as long as you don't dip them in butter or mayonnaise.

(Howard LeWine, M.D., is a practicing internist at Brigham and Women's Hospital, Boston, Mass., and Chief Medical Editor of Internet Publishing at Harvard Health Publications, Harvard Medical School.)

(For additional consumer health information, please visit www.health.harvard.edu.)


EASL 2012: New Data to Show Viral Cure Rates in the Most Difficult to Treat Hepatitis C Patients

April 05, 2012 03:00 AM Eastern Daylight Time

Boehringer Ingelheim to present five abstracts at ILCTM (EASL) including data on interferon-free treatment in genotype-1 patients and those with advanced disease

INGELHEIM, Germany--(BUSINESS WIRE)--For media outside of the U.S.A. only

Key data from Boehringer Ingelheim’s hepatitis C virus (HCV) clinical trial programme, HCVersoTM, focusing on interferon-free treatment, has been selected for inclusion in the official European Association for the Study of the Liver (EASL) press office activities. These data are one of five abstracts from a range of new Boehringer Ingelheim HCV data that have been accepted for presentation at the International Liver Congress (ILC)TM 2012, taking place 18th– 22nd April in Barcelona, Spain.

Boehringer Ingelheim’s accepted abstracts not included in EASL media activities can be accessed through the EASL website today, www.easl.eu. The Boehringer Ingelheim data included in EASL media activities will remain under embargo until the time of presentation on 21st April. All Boehringer Ingelheim’s data presentations are listed below.

Collectively, these data underscore the company’s focus on finding answers to the challenges faced by HCV patients.



Boehringer Ingelheim is continuing to support its aim of delivering a simpler HCV cure for all patients, including those toughest to treat through the company’s rigorous clinical trial programme; HCVersoTM.

For more information on Boehringer Ingelheim’s HCV portfolio, please visit www.boehringer-ingelheim.com and follow the company on Twitter www.twitter.com/boehringer.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.

In 2010, Boehringer Ingelheim posted net sales of while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.


Boehringer Ingelheim GmbH
Julia Meyer-Kleinmann
Director Corporate Communications
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com