Experts Support First U.S. Bird FLU Vaccine

27 February 2007 (Reuters Health [Susan Heavey])—The first potential bird flu vaccine for humans to help prevent a widespread outbreak in the United States won support from US experts as an interim measure until better versions come along.

The experimental vaccine, made by Sanofi-Aventis, would be the only US-approved vaccine for the H5N1 influenza virus in case of a pandemic if the Food and Drug Administration (FDA) later approves it.

The panelists overwhelmingly said Sanofi's version was effective and safe enough given that it is the only option right now.

About 45% of the 91 people inoculated with the bird flu version had an immune system response, according to the FDA. Forty-two patients received a placebo.

The FDA will weigh their recommendations as it makes its approval decision, but it usually follows the advice of its panels.

Sanofi's vaccine would not be sold commercially. Instead, the federal government could stockpile it in case of a pandemic or for those at higher risk to contract the H5N1 virus. Adults aged 18–64 would receive 2 injections 28 days apart.

At the meeting, Health and HumanServices officials said they were seeking 20 million doses to first innoculate critical workers, as well as about another 600 million doses, or enough for all citizens, within 6 months of an outbreak.

While the panel supported Sanofi's vaccine, FDA officials said better vaccines with more robust protection would eventually displace it.

Glaxo and Novartis are developing such versions using novel adjuvants, while Iomai Corporation has a skin patch to boost vaccine impact. Sanofi said it was also working on different dosing and newer technology, as well as adjuvants—substances added to vaccines to boost immune system response.

FDA staff expressed concern that the immune response among patients to Sanofi's vaccine was not as strong as to its seasonal flu counterpart. Its effect on women, minorities, and those who had seasonal flu shots was also unknown, they added.

Glaxo Bird FLU Shot Fights Different H5N1 Strains

5 March 2007 (Reuters Health [Ben Hirschler])— An experimental bird flu vaccine for humans provides substantial cross-immunity against “drifted” strains of the virus, suggesting it may provide protection in the event of a pandemic.

Britain's GlaxoSmithKline said clinical data from 2 studies showed its prepandemic shot was able to recognize and kill an Indonesia H5N1 strain that was genetically quite different from the Vietnam one included in the vaccine.

The finding is significant because it indicates the vaccine—which contains a special adjuvant—may help the body's immune system resist future variants of H5N1.

Data released at an international medical meeting in Hong Kong showed 77% of people given the vaccine with the Vietnam strain also had a strong antibody response to a separate Indonesia strain, 42 days after immunization.

The response was 25 times greater than that observed in patients given a nonadjuvanted vaccine.

A second study, involving ferrets, found the vaccine provided 96% cross-protection against a lethal challenge with the drifted Indonesia virus strain.

Glaxo, meanwhile, submitted its second- generation vaccine for approval in Europe in January.

Sanofi, Novartis AG, and Baxter International are also working on rival improved vaccines.

Editor's comment. It has been repeatedly observed that the immune response to the H5N1 vaccines is poor unless adjuvant is added. This and the preceding report indicate that adjuvanted vaccine is the way to go.

Sanofi Launches Cut-Price Malaria Pill for Africa

1 March 2007 (Reuters Health [Ben Hirschler])— French drugmaker Sanofi-Aventis has launched a new cheap and easyto- take combination pill to fight malaria that could help reduce deaths from the killer disease in Africa.

Sanofi is working with the Drugs for Neglected Diseases initiative (DNDi)—a group backed by charity Medecins Sans Frontieres—and will sell the drug at no profit for >$1 for adults and 50 cents for children >5 years old.

The 2-in-1 pill is designed primarily for Africa, where a child dies of malaria every 30 sec, but an amended form is also in the works for Latin America, South East Asia, and India, where there are different types of malaria.

The new medicine is a fixed-dose artemisinin- based combination, or ACT, that is more convenient and less expensive than currently available drugs. Sanofi's product combines artesunate with the older antimalarial amodiaquine.

In an unusual move for a drugmaker, Sanofi has decided not to patent the medicine, leaving the door open for generic companies to copy it and produce their own cheap versions.

(Additional reporting by Emma Batha)

Tamiflu Side Effect Concerns Grow after Deaths in Japan

6 March 2007 (Reuters Health [George Nishiyama])—Concerns that the influenza drug Tamiflu may induce fatal side effects are growing in Japan after 2 people who took the drug fell to their deaths last February.

The deaths, the latest cases of abnormal behavior by those who took Tamiflu, prompted the Health Ministry to issue a warning that influenza patients could show psychiatric problems, although it has denied the drug was responsible for them.

According to the Health Ministry, 54 people have died so far after taking Tamiflu, and in February, a 14-year-old girl and a boy fell to their deaths from their apartment homes in separate incidents after taking the drug. Neither had left a suicide note.

Swiss drug maker Roche Holding AG, which produces oseltamivir, has denied a link between the medication and the deaths, adding that influenza itself could cause psychiatric problems.

Roche spokeswoman Martina Rupp said that Tamiflu has been used to treat 50 million people since it was approved in 1999, and in 2005, there were only 103 reports of neuropsychiatric problems.

In November, the US Food and Drug Administration decided to require Roche to put a caution on Tamiflu labels urging close monitoring for abnormal behavior, such as delirium, although it said it was unknown if the drug contributed to the psychiatric problems.

(Additional reporting by Sam Cage in Zurich)

Clinical Benefits of Treating Primary HIV-1 Infection Still Unclear

1 March 2007 (Reuters Health [Deborah Mitchell])—The long-term benefits of starting antiretroviral therapy during primary HIV-1 infection have still not been confirmed. The results of 2 recent studies presented at the 14th Annual Retroviral Conference highlight the need to clarify this issue.

In the first study, Dr. Radjin Steingrover from the University of Amsterdam reported his group's findings for 332 patients with laboratory evidence of primary HIV-1 infection. Sixty-four started highly active antiretroviral therapy within 180 days of seroconversion. Thirty-two of these patients subsequently stopped treatment. The remaining patients delayed treatment.

A viral set point was reached 7 weeks after seroconversion or interruption of treatment. Compared with the untreated patients, the viral set point was 0.6 log copies/mL lower in those who interrupted early treatment (P > .001), Dr. Steingrover reported.

This lowering of viral set point following early treatment, he concluded, “indicates there are long-term clinical benefits to be gained” from this treatment strategy. No differences in CD4 cell counts were seen between the early and delayed treatment groups.

A factor that biased the results, Dr. Steingrover added, was that primary infection patients with high viral loads, known to be associated with a poor prognosis, were more likely to receive early treatment.

When asked how he would manage patients with primary infection, he said patients presenting with severe symptoms, requiring hospitalization, should probably start treatment immediately, whereas those with mild or no symptoms can probably wait until changes in HIV-1 load and CD4 counts begin.

Contradictory results were obtained in the second study, in which early treatment appeared to have no effect on viral set point. However, a beneficial effect on CD4 cell counts was noted.

Dr. Christine Koegl of MUC, Munich, and colleagues are following 200 patients with primary HIV-1 infection enrolled in 1 of 2 large ongoing trials. One hundred forty-four subjects began treatment immediately and 56 delayed treatment. So far, the team has followed the patients for a median of 27 months, Dr. Koegl said.

When 100 patients stopped therapy after 9.5 months, viral load was below detection in 82% and the median CD4 count was 799 cells/µL.

However, 12 months after treatment was stopped, the median viral load was up to 38,056 copies/µL, compared with 52,880 copies/mL in the untreated patients. Median CD4 values were 538 cells/ µL in patients who had been treated compared with 525 cells/µL in the untreated group.

“On the other hand, we have 3 patients (in the early treatment group) who are still undetectable,” Dr. Koegl said. These patients appear to have benefited from early treatment, “but we don't know why,” she added.

Overall, Dr. Koegl concludes that early treatment has no significant effect on viral load 12 months after treatment is stopped. However, compared with baseline values, the untreated patients had a median decline in CD4 count of 87 cells/µL, whereas the treated patients had an increase of 60 cells/µL, suggesting a beneficial immunologic effect.