January 1998
BETHESDA, Md. - The Food and Drug Administration (FDA) Anti-Infective Drugs Advisory Committee recently recommended for approval inhaled tobramycin solution (Tobi, PathoGenesis) for the management of cystic fibrosis (CF) patients who are infected with Pseudomonas aeruginosa.
In a unanimous vote, the committee agreed Tobi demonstrated adequate safety and efficacy to support approval for use in CF patients 6 years and older.
"I don't have any problems with the efficacy and safety and I think there's a need to have an [aerosolized] product approved," said Nancy K. Henry, MD, assistant professor of pediatrics and of laboratory medicine and microbiology, Mayo Clinic, Rochester, Minn.
However, the committee agreed additional recommendations should be conducted regarding toxicity.
Tobi is designed to expand the use of tobramycin beyond short-term hospitalizations to long-term, home administration to suppress serious pseudomonal infections common in CF patients.
If approved, this would be the first inhaled antibiotic solution indicated for treating CF patients with pseudomonal lung infections and would be the second drug approved for use in CF patients in the past 30 years.
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The committee reviewed safety and efficacy data from two phase 2 clinical trials of Tobi in CF patients whose lungs were infected with P. aeruginosa. A total of 468 patients in 69 cystic fibrosis care centers in the United States completed the trials. Treatment with the drug or a placebo was intermittent for six months, with patients on 300 mg of aerosolized treatment twice daily for four weeks, then off therapy for four weeks.
Compared with placebo, the results of the six-month studies indicated that inhaled tobramycin improved lung function by 11% by the end of the study and reduced bacterial levels in the sputum.
"The most important thing with these patients is that there clearly is improved pulmonary function which is the measurable and reproducible end goal," said Barth Reller, director of clinical microbiology, Duke University Medical School, Durham, N.C.
A combined analysis of both studies also showed a 36% decrease in days spent in the hospital and in use of intravenous antibiotics.
Overall adverse events were comparable between Tobi and placebo. Transient tinnitus and voice alteration were the only adverse events reported more frequently by the treatment group, which consisted of volunteers ages 6 to 63 years.
"My instinct would say the data certainly seems supportive of use for a six-month period," said committee member Carl W. Norden, MD, head of the division of infectious diseases, Cooper Hospital/University Medical Center, Camden, N.J. "I would be comfortable with the data we have right now to approve it for indications for longer use with the understanding that if the data shows the effect wanes and is no longer effective, that the indication would have to be changed."
Tobramycin has been administered intravenously to CF patients with lung infections for more than 20 years.
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