News (Updated June 7, 2009)

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South Africa leads hunt for killer TB vaccine

Reuters June 5, 2009

WORCESTER, South Africa (Reuters) - Baby Hisinawa is permanently semi-comatose after TB spread to his brain, his board-stiff body shivering as a doctor pushes a rubber tube down his nose to clear away thick phlegm choking him.

Last December, the chubby two-year-old South African was talking and laughing. Now he has limited use of all four limbs and cannot swallow.

Hisinawa is a severe example of the debilitating symptoms of tuberculosis, which kills more people than any other treatable infectious disease. Trials for a new vaccine start in South Africa in July.

Scientists across the world are seeking a new vaccine against the contagious lung disease, which is largely under control in developed countries but still haunts the poor in the developing world. Up to one in three people have it globally.

"The world needs a new TB vaccine because the current one is not really effective in terms of preventing TB and that is manifest in the context of an increasing epidemic," Gregory Hussey, director of the South African TB Vaccine Initiative (SATVI) told Reuters.

With more resources and research committed by international and philanthropic organisations like the World Bank and the Bill and Melinda Gates Foundation, optimism for a new TB vaccine has reached heights last seen when the current TB vaccine, Bacille Calmette-Guerin (BCG), was developed in the 1920s.

The most clinically advanced of the nine vaccine candidates -- called MVA85A -- will be tested in South Africa next month among 2,874 children under the age of one. Researchers hope to register a new anti-TB vaccine by 2015.

"All of the clinical trials conducted to date with this vaccine (MVA85A) have shown that it is safe and it stimulates high levels of the type of immune response we believe is protective against tuberculosis," the vaccine inventor Dr Helen McShane of the University of Oxford, told Reuters.

The World Bank, which focuses on controlling TB by identifying and curing infectious patients, has said financial support for its treatment would bring an estimated economic gain of around $1.6 trillion (996 billion pounds) between 2006 and 2015.

Without financial intervention, the economic burden of TB in badly hit countries like China could reach up to $1.2 trillion between 2006 and 2015, the World Bank said. Global efforts have been ramped up to meet a United Nations Millennium Development Goal of halving the global TB infection rate by 2015.

STALKING THE POOR

South Africa is a good place to start: a high rate of infection coupled with the world's largest AIDS epidemic, where close to an eighth of the population are HIV positive, makes it particularly vulnerable.

The World Health Organisation has said the AIDS virus and TB form a lethal combination, each speeding the other's progress. TB is the leading cause of death in AIDS sufferers.

"My friend has TB and I've seen what it does to her," said Esmerenthia Cupido, 35, a resident of the town of Worcester , 100km (63 miles) north of Cape Town , where one of the vaccines will be tested under SATVI, which is assessing four TB vaccine candidates in the global pipeline.

"She coughs terribly and is getting very thin. She also lost two of her brothers to the disease, but likes to party and drink. She doesn't want to listen," Cupido told Reuters at the Brewelskloof hospital in Worcester .

"Tering" as it is known in the local Afrikaans patois, stalks the poor. A lack of proper nutrition, cramped living conditions and substance abuse aid TB's spread.

In South Africa a visit to the local corner shop or popular neighbourhood drinking spot can be a dangerous gamble, should an infected adult sneeze or cough. The World Health Organisation has said South Africa has the world's highest TB incidence rate at 948 infections for every 100,000 people.

INEQUALITY

The government said on Wednesday it would step up measures to improve health care in Africa 's strongest economy.

"We have set ourselves the goals of reducing inequalities in health care ... and step up the fight against the scourge of HIV and AIDS, TB and other diseases," South Africa's president Jacob Zuma said in his first state-of-the-nation address.

TB, which has infected people for thousands of years according to the Global Tuberculosis Institute at the New Jersey Medical School , kills around 1.8 million people globally each year. Children and young adults are most vulnerable.

In the 21st century it has swamped developing countries across Africa and Asia , overwhelming fragile health care systems. It is firmly enmeshed in the social fabric of Worcester .

"About four months ago I saw someone in our street die from TB. He got thin and started vomiting blood. When he coughed, chunks of blood came with it," Monique Wilson, 26, said as she cradled six-month-old Mercedi. "That scared me and I decided to take my baby for vaccination."

The TB bacterium commonly affects the lungs, but can also move through the blood to other organs and the bones. When the brain is affected, as with baby Hisinawa, patients die or suffer serious disabilities.

The July tests will be the first concept trial of a new preventative TB vaccine for infants in close to 90 years, and will be used as a booster to the BCG shot if found to be successful.

Major drug pharmaceutical companies GlaxoSmithKline, Sanofi-Aventis and Crucell are now also testing TB vaccines, although there is little incentive to develop an unprofitable vaccine.

"Most of the market is in developing countries which might not be able to afford an expensive vaccine," said Dr Tony Hawkridge, Head of the Aeras Global TB Vaccine Foundation's Africa office.

"It's never going to be a Viagra or one of those multi-billion dollar products which rockets a company into the ranks of the very rich," he said.

(Reporting by Wendell Roelf; Editing by Farah Master and Michael Kahn)

 

GlaxoSmithKline signs potential $1 billion deal with US biotech company Concert

On Tuesday June 2, 2009, 1:03 pm EDT

LONDON (AP) -- GlaxoSmithKline PLC signed a potential $1 billion deal with U.S. biotech company Concert Pharmaceuticals on Tuesday to access deuterium-containing medicines, a deal that will beef up its pipeline of early stage drugs.

Glaxo will gain the rights to three research programs by privately held Concert -- a protease inhibitor for HIV due to start Phase I clinical trials this year, a preclinical drug for chronic kidney disease and a third unspecified product.

Deuterium is a safe, non-radioactive relative of hydrogen that can be isolated from sea water and has been used extensively in human metabolic and clinical studies.

As deuterium is heavier than hydrogen, it forms a stronger chemical bond to a carbon atom of a molecule, which may substantially improve a drug's metabolic properties, potentially resulting in better efficacy.

Patrick Vallance, senior vice president of drug discovery at Glaxo said that Concert's approach to deuterium modification of medicines "has broad potential to enhance certain drug properties and result in innovative new medicines."

Lexington, Massachusetts-based Concert said it would receive $35 million upfront, including a $16.7 million equity investment.

The company is also eligible to receive milestone payments and tiered, double-digit royalties based on deuterium-containing products arising from the Concert pipeline programs and from any Glaxo pipeline compounds.

Combined with the upfront payment, Concert said it has the potential to receive in excess of $1 billion.

Concert will retain full rights to further develop and commercialize its product candidates in any program that Glaxo chooses not to license.

 

FDA releases list of potential drug risks

Thu Jun 4, 2009

By Lisa Richwine

WASHINGTON (Reuters) - U.S. regulators on Thursday listed two dozen drugs, including weight-loss medicines and sleep disorder pills, that it is at an early stage of reviewing for potential safety problems.

Many of the issues have been previously disclosed, but remain under review by the Food and Drug Administration.

The FDA said it was checking Pfizer Inc's smoking cessation drug Chantix for possible risk of accidental injury, vision impairment and other issues, and Cephalon Inc's sleep disorder drugs Nuvigil and Provigil for a potential of serious skin reactions.

Other drugs listed included orlistat, a weight-loss drug sold by Roche Inc as the prescription product Xenical and by GlaxoSmithKline Plc as the over-the-counter drug Alli. The FDA said it was continuing to evaluate liver toxicity reports for orlistat.

The FDA also said Pfizer's overactive bladder drug Detrol was under investigation for reports of Stevens-Johnson syndrome, a serious skin reaction.

The FDA releases a quarterly list of safety probes as part of an effort to inform the public about early investigations of potential side effects that have been reported. The list released on Thursday covers October through December 2008.

The problems are potential safety issues and their appearance on the list "does not mean that FDA has identified a causal relationship" with the drug, the agency said.

Roche spokesman Terry Hurley, commenting on the listing of Xenical, said available data "does not suggest that orlistat is causally related" to liver problems, noting obesity itself is a risk factor for liver injury.

Glaxo spokeswoman Mary Anne Rhyne also said "no causal relationship ... has been established" between Alli and hepatitis, a liver disease.

Pfizer spokeswoman Sally Beatty said the maker of Chantix evaluates any reports of health problems and "as with all our medicines, we work with the FDA to ensure our labeling reflects the latest safety information."

The FDA had said last year it was taking a closer look at Chantix after reports of accidents, vision loss and other problems in hundreds of patients

A Cephalon spokeswoman did not immediately respond to a request for comment on Nuvigil and Provigil. Serious skin reactions were identified as an issue with the drugs in 2007 and the FDA continues to study the matter, the agency said.

A spokeswoman for Glaxo could not immediately be reached for comment on the listing of Alli.

Bristol-Myers Squibb Co's HIV drug, Sustiva, was listed due to one report of an eye-related birth defect. A description of the case was added to the drug's prescribing instructions in March 2009, the FDA said.

Bristol-Myers spokeswoman Cristi Barnett said the drug's label states it should only be used in pregnant women, "if the benefit to the patient justifies the potential risk to the fetus."

The FDA also is probing pancreatitis with Bayer AG's contraceptive Yasmin, the agency's list said. Bayer spokeswoman Rose Talarico said the listing "was not prompted by any change in the existing safety profile" of Yasmin and the company "continues to work with the FDA to ensure that the most up-to-date and accurate safety information" is included in the drug's label.

(Reporting by Lisa Richwine and Lewis Krauskopf; Editing by Gerald E. McCormick, Gary Hill)


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