FDA Extends Prophylaxis Indication for Tamiflu to Children

U.S. Food and Drug Administration Extends Prophylaxis Indication for Tamiflu to Children Between One to 12 Years of Age

NUTLEY, N.J., December 21, 2005 -- Roche announced today that the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) extending the prophylaxis (prevention) indication for Tamiflu (oseltamivir phosphate) to include children ages one through 12. The leading prescription antiviral medication for prevention and treatment of influenza, Tamiflu was previously approved for prophylaxis in adolescents (age 13 years and older) and adults. Tamiflu is also the only antiviral medication indicated for the treatment of influenza type A or type B infection in patients one year and older, and is available in both capsule and liquid suspension formulations.

"These new data support the important role of Tamiflu in reducing the spread of influenza, both among children and adults," said Dominick A. Iacuzio, Ph.D., medical director at Roche. "As we head into the height of cold and flu season, the pediatric prophylaxis indication gives doctors and patients an important new tool to help manage the flu virus."

When administered within 48 hours of exposure, clinical data show that prophylaxis with Tamiflu reduced the incidence of flu from 17 percent (18/106) in the group not receiving Tamiflu to 3 percent (3/95) in the group receiving prophylaxis. The dosing for the new indication is 30 mg to 60 mg once daily (dependant on body weight) for a duration of 10 days. Therapy should begin within two days of exposure, following close contact with an infected individual.

The sNDA was filed based on results from a subset of pediatric patients in a clinical study where Tamiflu was used for the management of influenza in households. The study, which included more than 1,000 patients (including adults and children), showed that post-exposure prophylaxis is effective in preventing secondary spread of influenza infection and illness in households and that the protective efficacy of Tamiflu was the same in children aged one through 12 as the whole population.

Safety/Labeling

The FDA Pediatric Advisory Committee last month confirmed the safety of Tamiflu in children, following a standard data review. As part of the Post Approval Commitment (PAC) for the new indication, Roche will provide the FDA with safety information on 40 to 50 patients between one and 12 years of age using the approved prophylaxis dosing for up to six weeks.

A separate review of the safety data by the European Medicines Agency (EMEA) also concluded that there was no new safety signal relating to psychiatric disorders and Tamiflu use, therefore recommending no change to the product safety information. Tamiflu received a positive opinion from the EMEA's Committee for Medicinal Products for Human Use for extending the use of Tamiflu to include prevention of influenza in children age one to 12 years.

In clinical studies, gastrointestinal events, particularly vomiting, were the most frequently reported adverse events in pediatric patients.

The updated Tamiflu label will also include a precaution related to anaphylaxis and serious skin reactions, based on adverse skin events that have occurred in a small number of patients.

To date, Tamiflu has been used by about 33 million patients worldwide, 13 million of whom are children.

Flu's Impact on Children

According to a new study in the New England Journal of Medicine, "Children constitute both a population that is highly vulnerable to influenza infection and one of the most important links in its transmission. Control measures for interpandemic and pandemic influenza such as vaccines and antiviral drugs, need to be effective and applicable to the youngest among us."¹

Prevention of influenza in children can have a significant impact on the spread of influenza in the household and the whole community. It is estimated that children are three times more likely to get sick with the flu -- on average, one in 10 adults is affected by influenza annually, compared with one in three children. Children younger than two years old are as likely as those over age 65 to be hospitalized because of the flu.²

How Tamiflu Works

Tamiflu works by targeting one of the two major surface structures of the influenza virus, the neuraminidase protein. The neuraminidase site is virtually the same in the most common strains of influenza, types A and B. Tamiflu attacks the influenza virus and is thought to work by stopping it from spreading inside the body. Tamiflu treats flu at its source, by attacking the virus that causes the flu, rather than simply masking symptoms. When taken within two days of the onset of symptoms, Tamiflu can reduce the duration and severity of the flu. Frequently reported adverse events include nausea and vomiting.

About Tamiflu

Tamiflu, co-developed by Gilead Sciences, Inc., based in Foster City, CA, is a systemic treatment for the most common strains of influenza (types A and B). The leading prescription oral antiviral drug, Tamiflu is indicated for treatment of type A and B influenza in patients one year and older. Tamiflu is an effective treatment, and can reduce the duration and severity of the flu when taken within two days of symptom onset. Tamiflu, a neuraminidase inhibitor, works by attacking the influenza virus and its ability to replicate, rather than simply addressing influenza symptoms.

Tamiflu is also approved for the prevention of influenza in adults and children one year and older. Clinical trials have shown Tamiflu is effective in preventing influenza illness when taken once daily for at least ten days. For the prevention of influenza in those 13 years or older, Tamiflu is administered following close contact with an infected individual who demonstrates characteristic symptoms of influenza, and based on knowledge that influenza is circulating in the area for 10 days, or up to six weeks for seasonal prophylaxis. For the prevention of influenza in children age one to 12, Tamiflu is administered for 10 days following close contact with an infected individual.

Tamiflu is generally well tolerated. In treatment studies in adults, the most frequently reported adverse events were mild-to-moderate transient nausea and vomiting. Other events reported more frequently than with placebo were bronchitis, insomnia and vertigo. In prophylaxis studies in patients aged 13 and older, adverse events were qualitatively similar to those seen in the treatment studies despite a longer duration of dosing. Events reported more frequently in subjects receiving Tamiflu compared to subjects receiving placebo in prophylaxis studies included nausea, vomiting, diarrhea, abdominal pain, dizziness, insomnia, headache, vertigo and fatigue.

In pediatric treatment studies, the most frequently reported adverse event was vomiting. Other events reported more frequently by pediatric patients treated with Tamiflu included abdominal pain, epistaxis, ear disorder and conjunctivitis. These events generally occurred once and resolved despite continued dosing. Adverse events in pediatric prophylaxis studies were consistent with those observed in pediatric treatment studies.

Rare cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnsons syndrome, and erythema multiforme have been reported in post-marketing experience with Tamiflu. Tamiflu should be stopped and appropriate treatment instituted if an allergic-like reaction occurs or is suspected.

Efficacy of Tamiflu in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established.

Tamiflu was approved by the U.S. Food and Drug Administration (FDA) for the treatment of uncomplicated acute illness due to influenza infection in adults in October 1999. The FDA granted marketing approval for the prevention of naturally occurring influenza A and B in adults and adolescents 13 years and older in November 2000. The FDA granted marketing approval of the oral suspension for use in the treatment of influenza A and B in children one year and older in December 2000. In December 2005, the FDA extended the prophylaxis indication for Tamiflu to children age one to 12 years. Tamiflu oral suspension is used for pediatric patients one year and older or adult patients who cannot swallow a capsule. Tamiflu is the first and only liquid suspension to treat influenza A and B.

Vaccination is considered the first line of defense against influenza.

Tamiflu is available for the treatment of influenza in more than 40 countries worldwide.

For more information, please visit www.Tamiflu.com

1. Dolin, R. Influenza - interpandemic as well as pandemic disease. N Engl J Med 353; 24. p. 2535-7. (December 15, 2005).
2. Thompson, WW et al. Influenza-Associated Hospitalizations in the United States. JAMA 2004; Vol. 292, No. 11; 1333-40.

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