Drug companies push to make inhalers CFC-free
The federal government is mandating the replacement of chlorofluorocarbons (CFCs) in pressurized metered-dose inhalers because of CFCs’ role in destroying ozone and allowing excessive radiation to reach the earth’s atmosphere.
That has sent inhaler manufacturers hurrying to find new ways of delivering corticosteroids to the lungs. "The process has created formidable technical challenges as well as new opportunities for potentially improved aerosol delivery," wrote Donald P. Tashkin, MD, FCCP, professor and chief of the Division of Pulmonary and Critical Care Medicine at the UCLA School of Medicine in Los Angeles. His comments were part of an editorial in the February issue of the journal CHEST.
The same issue featured a 12-week study that shows hydrofluoroalkane-134a (HFA-134a) beclomethasone dipropionate (BDP) may treat asthma as well as traditional CFC-BDP-propelled drugs — using half the daily dose.
Besides being CFC-free, the new inhaler can deliver the medication into the smaller airways, which may not receive adequate treatment using today’s inhalers.
Lower doses possible
"This may more effectively treat the disease. That may be why we can get away with the lower dose," says Gary Gross, MD, of the Dallas Allergy and Asthma Center and lead investigator of the study published in CHEST. "The part of the disease that may not be appropriately treated are those very peripheral airways."
In the study, 347 patients were given either an HFA placebo, 400 mcg a day HFA-BDP, or 800 mcg a day of CFC-BDP over 12 weeks.
Of those patients, 113 received HFA-BDP, 117 received CFC-BDP, and 117 received HFA placebo. Patients in each group were similar in their characteristics, including lung function.
CFC-BDP and HFA-BDP provided equivalent asthma control, which was measured by symptom scores for wheezing, coughing, shortness of breath, and chest tightness. The numbers of symptom-free days and nights also were equivalent.
Morning peak expiratory flow measurements showed equivalent asthma control. And the numbers of symptom-free days and nights also were equal.
HFA-BDP proved more successful at delivering the medication to the smaller airways, a finding that mirrors results of an earlier study. That’s likely because the HFA-134a solution distributes smaller particles.
The study noted that targeting the smaller airways with anti-inflammatory agents appears to be the most promising treatment strategy of the future.
Opening up new possibilities
"It opens up new treatment possibilities," Gross says. "It’s exciting because just having a medication of a different size has such an impact on the way it is distributed to the lungs and airways."
Tashkin adds that potential has practitioners excited. "I sense that there is real interest in its potential for improving function in peripheral airways that are poorly penetrated by conventional steroid aerosols."
In addition, if using half the dosage yields the same results, that could benefit patients and manufacturers. "The most obvious advantage is a savings in cost (at least to the manufacturer) since only half the amount of HFA-based medication compared with CFC-based medication would be required to produce the same benefits," Tashkin wrote.
Opportunity for step-down prescribing
But it also means that once the inhalers are on the market, practitioners should prescribe lower dosages, keeping in mind they’re dealing with a treatment that’s twice as potent.
"All of us are trying to [give] the lowest effective dose for inhaled corticosteroids," Gross says. "This may be an opportunity to do step-down more effectively."
Reducing the amount of medication also could curb systemic side effects as less aerosol is deposited in the throat and then swallowed and because of lower total doses would be needed for comparable efficacy.
In a partnership agreement, Hoechst Marion Roussel and 3M Pharmaceuticals will co-promote a line of CFC-free asthma products in the United States, pending approval from the U.S. Food and Drug Administration. They also will co-promote the products in Canada, Australia, and New Zealand.
Precisely when the inhaler may come to market and how much it will cost remain unclear. However, the inhaler may be available later this year or early 2000, a spokeswoman for the companies says.
Safety still topic of study
In the study, the two treatment types also were comparable in terms of safety issues with no unexpected adverse events reported. Gross adds that further study is being done to look at these issues.
Adverse events possibly related to the study medications were reported by 52 patients total, or 15% of the group. They occurred in 11 patients treated with HFA-BDP, 23 treated with CFC-BDP, and 18 treated with the HFA placebo.
The study reported the safety profile of HFA-BDP compared favorably with that of CFC-BDP and there were no drug- or propellant-related safety concerns. But Gross and Tashkin caution more study is needed.
Among important issues that must be examined further include studies comparing efficacy vs. side effects of HFA-BDP as it relates to other inhaled steroid treatments.
Also, because of its influence on small airways, further studies need to address the long-term impact of this new delivery mechanism on these airways.
"The true clinical significance of these findings must await further studies," Tashkin says.
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