September 5, 2011 — In a 13-to-1 vote, a US Food and Drug Administration (FDA) advisory panel today said that evidence supports the safety and efficacy of tobramycin inhalation powder (TIP; TOBI Podhaler, Novartis) in the management of cystic fibrosis (CF) patients infected with Pseudomonas aeruginosa.
The votes were cast today in a meeting of the FDA's Advisory Committee for Anti-Infective Drugs, held in Silver Spring, Maryland.
During the meeting, data were presented from the C2301 and C2303 trials, which were designed to demonstrate superior efficacy of TIP to placebo in forced expiratory volume in 1 second (FEV1), microbiological activity, and clinical outcomes, and the C2302 trial, which compared inhaled tobramycin dry powder to nebulized tobramycin solution with respect to safety, microbiological activity, pharmacokinetics, and clinical outcomes.
Tobramycin inhaled solution (TOBI, Novartis) was approved by the FDA in 1997 for Pseudomonas aeruginosa infection in patients with CF. Both the TIP and TOBI formulations are delivered twice daily, but TIP is delivered via a "Podhaler," a hand-held, pocket-sized device, in a dry-powder formulation, whereas the inhaled solution is delivered through a nebulizer.
At the meeting, panelists voted on the question, "Has the applicant demonstrated adequate evidence of safety and efficacy to support the use of TIP in the management of cystic fibrosis patients infected with Pseudomonas aeruginosa?" The vote carried with 13 in favor, 1 against, and no abstentions.
Panel member Sheldon L. Kaplan, MD, with the Department of Pediatrics at Baylor College of Medicine in Houston, Texas, said that he voted "yes" "because I think that there was adequate evidence that TIP is equivalent to TOBI, primarily looking at microbial decline in colony-forming units and there was also demonstrated improvements in FEV1."
According to Dr. Kaplan, adverse events seen in the trials included cough, which is often related to CF itself. He added that TIP simply represents a treatment option; "If patients can't tolerate this particular formulation, they always can go back to the suspension," he said during the meeting.
Michael N. Neely, MD, Assistant Professor of Clinical Pediatrics at the University of Southern California in Los Angeles, who also voted "yes," said that he "felt that efficacy and safety [of the 2 formulations] were likely to be similar."
"I think it is obviously a simpler device to use, although I am not sure that this is going to improve adherence," he added.
"In the end, I think safety and efficacy were proven today by the sponsor," said panel chair Thomas A. Moore, MD, FACP, FIDSA, Clinical Professor in the Department of Medicine at the University of Kansas School of Medicine in Wichita.
The one panelist who voted "no" was Rodney Mullins, National Director of Public Health Consultants and Advocates in Duluth, Georgia. He stated that "it looked to me that we were making compromises...based on limited data." He added that "25 weeks is not long-term usage," and "we cannot reassure the American public," about safety and efficacy.
Prior to the actual voting question, the panel discussed the implications of the changes in minimum inhibitory concentrations (MICs) seen after treatment with TIP compared to tobramycin solution for inhalation.
Panel chair Dr. Moore summarized the panel's comments during the discussion, stating that MIC does not appear to be an ideal parameter to use for the study.
"Although the MIC data is interesting and certainly worth exploring further, clinically speaking it does not have great relevance at this point," he said.
The FDA does not always follow the advice of their advisory panels, but it usually does.
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Cite this: FDA Panel Votes in Favor of Tobramycin Powder in Cystic Fibrosis - Medscape - Sep 05, 2012.