sep07-4-1

NEW YORK (Reuters) - Merck & Co has halted testing of its experimental HIV vaccine, long considered one of the most promising vaccines in development, after a monitoring board found it was ineffective, the company said on Friday.

The failed tests represent a major setback in the global effort to stem infections with the virus that causes AIDS. Merck had expressed great optimism for the vaccine, which it has been testing for a decade.

The independent Data Safety Monitoring Board, after reviewing interim results of the study of the vaccine, recommended discontinuing vaccinations of volunteers as the trial was headed for failure, Merck said.

"No one really knows when and if we will ever have an effective HIV vaccine because the virus is such a great challenge," Mark Feinberg, vice president of medical affairs at Merck's vaccine unit, said in an interview.

The vaccine consisted of a common cold virus loaded with three proteins found in the HIV virus.

"The concept was that if someone getting the vaccine is later exposed to HIV, the immune system would recognize those HIV proteins and go after the virus," said Keith Gottesdiener, another senior Merck research executive.

Asked if Merck would attempt to develop other HIV vaccines in the wake of the failed trial, Gottesdiener said, "At this point, we can't give an answer; we're just starting to look at this data and all its implications."

The New Jersey-based company, which was developing the product in partnership with the federally funded HIV Vaccine Trials Network, said two other early-stage trials of the vaccine had also been discontinued.

Study investigators have been instructed to discontinue vaccinating volunteers and to monitor them, Merck said.

The study was aiming to determine whether the vaccine prevented HIV infection and whether it reduced the amount of virus in those who developed infection.

Although a number of medicines have been introduced in recent years that control the virus and keep symptoms of the otherwise fatal disease at bay, doctors have said a preventive vaccine is by far the best way to control continued spread of the disease.

The HIV Vaccine Trials Network, the largest clinical trials program for developing and testing HIV vaccines, helps coordinate vaccine efforts around the world.

"Today is a very sad day for the industry because Merck's vaccine had shown an ability to turn on the immune system, which gave many people optimism it would work," said Sarah Alexander, a spokeswoman for the trials network.

Although more than two dozen other HIV vaccines are now being tested for safety in human trials, only one is far enough along in trials to be tested for actual effectiveness, said Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition.

"The Merck vaccine was a step along the way that will give us clues how we can better trigger the immune system with other vaccines," Warren said.

An HIV vaccine formerly deemed to hold promise, developed by U.S. biotech company VaxGen Inc, was declared a failure in late 2003.

Millions of people have succumbed to AIDS since it started becoming prevalent in the early 1980s, with the worst outbreaks in Africa. The virus is now believed to be spreading quickly in India, China and other parts of Asia, fueled by unprotected sexual contact, prostitution and shared needles among drug users.

As many as 1 million Americans are believed infected with the virus. Many have insurance that covers the costly drug cocktails needed to prevent uncontrolled growth of the virus. But the drugs, which can cause serious side effects, must be taken for life because they cannot totally eradicate the quickly mutating virus.

Merck's discontinued international trial, called STEP, involved 3,000 HIV-negative volunteers from diverse backgrounds, between the ages of 18 and 45, at high risk of HIV infection.

An interim efficacy analysis, conducted in about 1,500 volunteers expected to have the best response to the vaccine, showed the drug was ineffective.

Although the vaccine has been a major hope among the medical community, it was not deemed to have major commercial potential, and Merck shares were little affected by the news. The shares closed up 44 cents to $51.82 on the New York Stock Exchange.

HIV prevention could save millions in Africa

WASHINGTON (Reuters) - Using drugs to prevent HIV infection could prevent as many as 3 million new cases in Africa if it was done right, researchers predicted on Tuesday.

A daily pill would not even have to prevent infection all the time to have this effect, if it was given to the right people with the proper counseling, the team at the University of Pittsburgh School of Medicine and at Imperial College London said.

"If you do it right, you can prevent lots of infections," Pittsburgh's Dr. John Mellors, who helped direct the study, said in a telephone interview.

The researchers wanted to know if a potential new approach called pre-exposure chemoprophylaxis, or PrEP, would work in a real-world setting.

Studies in monkeys suggest that an HIV drug called tenofovir, made by California-based Gilead Sciences Inc. under the brand name Viread, can keep a healthy animal or person from becoming infected with the incurable virus.

"We looked at a huge range of variables -- the efficacy of PrEP, how quickly the population gets on it, whether they stay on it, what population you target," Mellors said.

"One of the most important things we found is if you target the two highest risk groups, about 18 percent of the population, you have the most cost-effective approach."

For the most part, this means young men who have many different sexual partners.

The AIDS virus infects close to 40 million people globally and it has killed 25 million. Sub-Saharan Africa has about 63 percent of all cases.

But taking a daily pill -- or perhaps using a drug vaginally or rectally -- can also prevent infection.

"Our analyses indicate that approximately 2.7 to 3.2 million new HIV-1 infections could be averted in southern sub-Saharan Africa over the next 10 years by targeting PrEP to population groups with the highest sexual activity concomitant with preventing increased risk behaviours in those on PrEP," the researchers wrote in their report, published in the online Public Library of Science journal PLoS ONE.

Such a program would require intensive counseling to find out who the most sexually active people were and to ensure that the medication did not give people a sense of invulnerability, Mellors said.

"If the public feels that they can take a pill and now have more sex, the effect of the PrEP will go way down," he said.

Their model simulated a real-world African country where 20 percent of the adult population was infected.

In the best-case scenario, PrEP was effective 90 percent of the time and used by 75 percent of the sexually active population. The computer model predicted a 74 percent reduction in new infections.

The group predicted this would cost $2 billion over 10 years for southern Africa.

If PrEP worked just 30 percent of the time and was used by 25 percent of the sexually active population, it would only prevent 3.3 percent of new infections.

Groups are testing tenofovir as a preventive agent in people, both as a daily pill and as a topical cream that people could use vaginally and rectally.

J&J says Prezista matches Kaletra in HIV trial

NEW YORK (Reuters) - Johnson & Johnson said on Tuesday its drug Prezista was as effective in a late-stage trial as Abbott Laboratories Inc's Kaletra in cutting HIV to undetectable levels among patients not previously treated with HIV drugs.

Prezista, a once-daily protease inhibitor recently introduced by J&J, was given to patients along with Abbott's older protease inhibitor Norvir (ritonavir) and Gilead Science Inc's widely used Truvada. Truvada itself contains two drugs belonging to a separate class of HIV treatments called nucleoside reverse transcriptase inhibitors.

Another group of patients was given Kaletra, a top-selling HIV pill that combines Norvir with the protease inhibitor lopinavir, as well as Truvada.

J&J said levels of HIV dropped to undetectable levels after 48 weeks among 84 percent of patients taking experimental 800-milligram doses of Prezista, compared with 78 percent of those receiving Kaletra.

Data from the so-called ARTEMIS trial - the first study to test Prezista among patients never previously treated with other HIV medicines - were presented in Chicago at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Prezista was launched last year as a treatment for adults whose HIV infection had not been adequately controlled by prior treatment with other HIV drugs. Data from the new trial could eventually support its use as a first-line treatment.

Kaletra - approved for adults and children over 6 months of age, both as a first-line treatment and for those who have failed to benefit from other drugs - is the world's best-selling HIV protease inhibitor product. It had global sales last year of $1.14 billion.

Abbott spokeswoman Ilke Arici said Prezista's showing of "non-inferiority" to Kaletra in the trial was somewhat questionable because the trial design did not reflect how the drugs are given in real-world medical practice.

For instance, Arici said, many patients were given a soft gel form of Kaletra in the study, which she said is less effective than a new tablet formulation now widely used in the United States.

J&J spokeswoman Pam Van Houten acknowledged that most patients taking Kaletra began on the soft gel form and were later switched to tablets after that new Abbott formulation became available.

Van Houten noted that the label for Prezista recommends patients take two of the 600-milligram tablets, for a total daily dose of 1,200 milligrams.

But she said a lower total daily Prezista dose of 800 milligrams was used in the new study, on the theory that a lower dose would suffice for such patients who have not previously taken HIV drugs and therefore developed resistance to them.

Van Houten said J&J aims by the end of 2007 to ask U.S. regulators, based on the new data, to approve the use of Prezista for patients never previously treated for their infections with the virus that causes AIDS.

New anti-AIDS drug unveiled

Tue Sep 18, 5:40 PM ET

Pharmaceuticals giant Pfizer Tuesday unveiled a new anti-AIDS drug which it said could help HIV patients stay healthy for longer.

Selzentry is the first new class of oral HIV medicines to be introduced in more than 10 years, Pfizer said at an annual medical conference in Chicago.

After a 48-week trial, nearly three times as many patients receiving the drug combined with traditional medication recorded undectectable levels of HIV virus, compared with those just getting the normal treatments.

"The safety and durability of response seen with Selzentry ... in our study is reassuring. This drug is an important new weapon for clinicians who treat HIV," said Jacob Lalezari, director of Quest Clinical Research, at the University of California.

The US Food and Drug Administration in August approved the use of Selzentry, which is the first in a class of drugs called CCR5 antagonists. They prevent the virus from entering the body's T-cells, rather than fighting the virus once it is already infected the cells.

The drug does not however cure HIV infection or prevent it from being passed to another person, the company warned.

The side-effects are similar to those experienced with other anti-AIDS drugs, including nausea, fatigue, headaches and diarrhea.

Experts believe the eventual sales of the drug could generate 500 million dollars for Pfizer annually by 2011. The company is also seeking permission for worldwide sales.

Doctors report breakthrough drug treatment for TB

by Jean-Louis SantiniWed Sep 19, 8:31 AM ET

A new regime of antibiotic drugs appears to dramatically shorten the time needed to cure tuberculosis from six months to just four, according to research unveiled at a medical conference here Tuesday.

A team of Brazilian and US TB experts reported at a meeting of the American Society for Microbiology that adding the drug moxifloxacin to a standard cocktail of antibiotics increased by 17 percent the number of patients who cleared active TB infection from their lungs, to 68 percent from 85 percent.

The new combination drug therapy uses moxifloxacin in the place of an older, more traditional anti-TB drug, ethambutol.

The drug mixture shortened by two months the time needed to cure the highly infectious lung disease, experts reported at a meeting here of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

"This is the most compelling evidence in nearly 25 years that a novel antibiotic drug combination works better than the current gold standard at curing active TB infection," said study senior author Richard Chaisson, a professor of medicine, epidemiology and international health at The Johns Hopkins University School of Medicine.

"Beyond the obvious value of healing patients more quickly, a shorter treatment time could also cut down on transmission of the disease to others and make it easier for health care workers worldwide, who are overwhelmed by large numbers of patients, to treat more people and to treat them faster" said Chaisson, who also heads Hopkins's Center for Tuberculosis Research.

He noted that worldwide, nearly nine million new cases of TB are diagnosed each year, and more than one and a half million people die from the disease.

Tuberculosis can be particularly lethal for those with HIV and AIDS. The lung ailment has reached epidemic levels in developing countries with the high HIV infection rates.

The study of more than 170 TB-infected men and women in Rio de Janeiro, Brazil found after two months of combination therapy that patients who had taken moxifloxacin were significantly less likely have evidence of live TB bacteria in their bodies that patients on traditional ethambutol therapy.

Conventional TB therapy usually involves a six-month course of antibiotics, typically about four drugs in combination -- a treatment which cures about 95 percent of patients on average.

Substituting moxifloxacin not only appears to be faster and more effective, but also is also less expensive -- a major consideration for TB treatment in developing countries.

The shorter course of medication also increases the likelihood that patients will complete their therapy, thereby risking contracting and spreading drug-resistant strains of TB.

Germ resistance conference to begin in Chicago

by Jean-Louis SantiniMon Sep 17, 11:43 AM ET

Thousands of physicians and scientists began meeting here Monday to debate ways to fight bacteria resistant to drugs and the effects of global-warming on germs.

The American Society for Microbiology meeting is billed as the world's biggest conference on disease-causing microbes.

For the first time at the annual event, "the keynote session is going to be on climate change and the impact on human disease," Jim Sliwa, spokesman for the American Society for Microbiology which is organizing the event, told AFP.

"We know that climate change is going to change the pattern of infectious diseases," he said.

"As global average temperature increases, we know ... for example, the malaria line in mountainous regions will continue to rise," he said.

"We know also in the tropics influenza is year-round. There is no influenza season, so as the temperature rises the tropical areas expand and we'll get more year-round influenza."

Presentations at the conference, which is expected to draw some 12,000 physicians, researchers and health care professionals, will address the problem of drug-resistant microbes such as tuberculosis, which kills two million people each year.

Pharmaceutical labs will present research on growing challenges such as the resistance of certain staphylococcus bacteria, known as SARM, to antibiotics -- a source of many in-hospital infections, the association said.

They will also discuss the risks of a possible epidemic of a form of bird flu, that is dangerous to humans and that could be passed from person to person.

Also on the agenda is the results of clinical trials on the effectiveness of anti-retroviral therapies on cancers in people with HIV, the virus that causes AIDS.

British researchers meanwhile were to make a presentation on the antibiotic effects of statin drugs, which reduce cholesterol. Research seems to have revealed the mechanism by which chemical action of the liver gives the anti-cholesterol drugs anti-microbe properties.

The association Monday released a study showing a drop in the number of Americans who regularly wash their hands after using public restrooms, considered a key step in preventive hygiene.

The observational study found that only about three US adults in four (77 percent) washed their hands in public restrooms, a six percent drop from a similar study in 2005.

About 88 percent of women washed their hands after a visit to the lavatory, compared to just 66 percent men.

The frequency of handwashing observed by researchers conflicted with what most adults reported: In a telephone survey, 92 percent of adults reported washing their hands in public restrooms, far more than the 77 percent actually seen scrubbing up.

Other studies have shown that a worldwide campaign launched in 2005 by the World Health Organization to prompt medical personnel to wash and disinfect themselves before touching a patient yielded encouraging results, according to the conference program.

Inadequate hand-washing among doctors and nurses is responsible for millions of infections in hospitals around the world.

Researchers from France, Japan, and Britain will be in Chicago for the conference, formally titled the Interscience Conference on Antimicrobial Agents and Chemotherapy, which runs through Thursday.

EU Experts: Lift Ban on Roche HIV Drug

BRUSSELS, Belgium (AP) -- European Union medicine experts on Thursday recommended lifting a temporary EU-wide ban on the sale of a Roche Holding AG anti-HIV drug that had been contaminated with a substance that can be harmful to health.

The European Medicines Agency, or EMEA, said it backed allowing Roche to sell Viracept again because the company had fixed manufacturing problems that saw some batches contaminated with too much ethyl mesilate. The substance can damage DNA and may trigger cancer.

Roche needs the backing of the EU's head office, the European Commission, before it can put Viracept -- the brand name for nelfinavir -- back on sale. It said the soonest it could do this would be early 2008.

Six patients had complained that batches of the drug gave off a strange odor. The company first learned of the problem in mid-May and withdrew the drugs -- sold on prescription to HIV patients -- after tests confirmed the contamination.

Roche tracked the problem to ethanol residues in a holding tank that led to higher doses of ethyl mesilate in batches produced toward the end of 2006.

In June, it recalled all packs of Viracept on sale in Europe, including packs patients had at home. The recall did not affect the use of Viracept in the U.S., where Pfizer Inc. (PFE) sells the drug, or Canada and Japan.

The company's license to market the antiviral drug was suspended in August when EU regulators said they were worried about the quality of the product, saying its safety could not be guaranteed until it saw new information from Roche.

EMEA said it had now assessed Roche's work to upgrade safety, verifying this with a factory visit. Roche has now changed the way it makes the drug so it will no longer use a holding tank and will check for the contamination at an early stage.

"As a result, the (agency) has been reassured that the cause of the contamination has been eliminated and that future production of Viracept would meet the required quality standards," the EU experts said.

Regulators had also asked Roche to do more research to establish how much ethyl mesilate was toxic for human health and recommended monitoring the patients who were exposed to the contaminated batches, and all children and pregnant women ever exposed to the product.

Roche has now set strict acceptable maximum limits for ethyl mesilate, EMEA said, and is investigating the harmful effects of the contaminant and will follow up with patients.