Although it's not yet possible to determine the final cost of potentially huge post-marketing studies to evaluate the safety of LABAs to treat asthma, it's clear they will not be cheap and will take resources away from other drug development programs.
Even so, the regulatory and political dynamics suggest that the three pharma companies with LABAs on the market will move forward with the studies - the first such trials FDA is requiring under new authorities granted by the FDA Amendments act of 2009 (FDAAA).
FDA has already concluded that monotherapy with long-acting adrenergic receptor beta 2 (ADRB2) agonists (LABAs) increases the risk of asthma-related exacerbations, including hospitalizations and death. The question now is whether the risk is mitigated when an inhaled corticosteroid (ICS) is added to the therapy.
There are strong opinions about the answer to that question, as was evident at a joint meeting of FDA's Pulmonary-Allergy Drugs and Drug Safety and Risk Management advisory committees on March 10-11.
At one end of the spectrum, Andrew Mosholder of FDA's Division of Epidemiology presented a case that LABAs should be removed from the market entirely and that any further study would be unethical. Mosholder made clear that the views he presented were his and those of David Graham of the FDA Office of Surveillance and Epidemiology, and not those of the agency or OSE.
On the other end were Thomas Alexander Platts-Mills and Jerry Krishnan, two pulmonologists who repeatedly questioned the need for any safety trials given the documented benefit of LABAs in asthma patients and what they deemed to be a lack of any evidence of a safety crisis.
Platts-Mills is director of the asthma and allergy disease center at the University of Virginia Medical Center, and Krishnan is associate professor of medicine and health studies at the University of Chicago. Both are voting members of the Pulmonary-Allergy committee.
The rest of the panelists fell between those two extremes. John Jenkins, director of the Office of New Drugs in FDA's Center for Drug Evaluation and Research (CDER), noted that this broad range of opinions was based on the same data, which is what prompted the agency to require the new trials.
"We knew that this was going to