Aerosol Drug Development
James Fink, Ph.D., an aerosol researcher who is currently a scientific advisor to Aerogen, talked about the continuing need for aerosol delivery of protein, peptides, and other drugs despite the barriers created by the commercial failure of Pfizer’s Exubera, the first inhalable insulin.
According to Dr. Fink, Exubera, approved for use by the FDA in January 2006, was intended to bridge the transition from oral medications to injected insulin. Pfizer removed it from the market less than two years later, citing limited acceptance by physicians, patients, and third-party payers.
Further, during Exubera’s clinical trial program, some Exubera-treated patients developed lung cancer. While all of the Exubera patients who developed cancer were former cigarette smokers, and the incidence in the Exubera group was lower than the broader demographic of cancer in smokers, the reports nonetheless led development partner Nektar Therapeutics to terminate its inhaled insulin programs.
Citing challenges of developing aerosol drug formulations in the post-Exubera world, Dr. Fink said that “within weeks following the Exubera cancer scare, all but one of the pharma companies announced their withdrawal from developing inhaled insulin products.” Further, he noted that, “the Exubera story dampened enthusiasm for pulmonary drug delivery programs with other large molecule proteins and peptides.”
Dr. Fink believes that Exubera’s, 17-year development saga provided some valuable lessons. Its dry powder formulation had an excellent shelf life, eliminating the cold-chain requirements associated with injectible insulin. Exubera, the first active dry powder inhaler, also provided high-efficiency lung delivery of drug independent of patient inspiratory flow. Most importantly, he said, Exubera proved that a large molecule protein could be inhaled multiple times each day with good therapeutic effect and minimal adverse events (in nonsmokers).
Dr. Fink described recent success with liquid aerosol immunization in the WHO/IVR-supported program for development of an aerosol measles vaccine. “Inhaled measles vaccine can provide five doses via inhalation versus one with the same volume of injected vaccine, with comparable immunogenicity,” he said.
“This program, now entering pivotal trials in India could ultimately support effective vaccination for up to 300 million children annually without risk of exposure to blood-borne pathogens.” Efforts are currently under way to develop dry powder options for inhaled vaccine delivery.
Despite setbacks with Exubera, Dr. Fink predicted an exciting era ahead for pulmonary delivery in the post-Exubera world.