By Frances Bishopp

Sepracor Inc. said it will file a new drug application (NDA) with the FDA in June to market levalbuterol for asthma based on results from its Phase III bronchodilation study that demonstrated an improved therapeutics index of its drug compared with racemic albuterol.

Sepracor also has completed a Phase II pediatric dose-finding trial in children with asthma aged six to 11, which, David Southwell, CFO at Sepracor, told BioWorld Today, will be another cornerstone for the NDA submission.

Levalbuterol is the purified, active-isomer form of the leading bronchodilator, racemic albuterol, sold as Ventolin (made by Glaxo Wellcome plc, of London) and Proventil (made by Schering-Plough Corp., of Madison, N.J).

Sepracor took albuterol, a drug launched in the mid-1970s, and purified it by taking out the deleterious left isomer, leaving the potent R isomer, Southwell explained.

The pivotal Phase III study confirmed the company's Phase II results and showed levalbuterol provides a greater improvement in lung function than racemic albuterol. In addition, at doses showing equivalent efficacy to the marketed racemic albuterol product, levalbuterol demonstrated significantly reduced beta-mediated side effects, such as pulse rate increase.

Sepracor's trial, involving 362 asthmatic patients at 32 sites, was designed as a parallel-group, placebo-controlled study. It compared two doses of levalbuterol with two doses of racemic albuterol inhalation solution given by nebulization, using standard measurements of efficacy and side effects for a four-week period in which patients were dosed three times a day. Lung function was measured at set intervals over an eight-hour period following the initial dose and periodically throughout the study.

The pediatric Phase II study was a 43-patient, double-blind, placebo-controlled crossover trial also comparing levalbuterol with racemic albuterol.

This trial compared four doses of levalbuterol, two doses of racemic albuterol, and a placebo delivered as an inhalation solution by nebulizer. Patients received single doses on four occasions. Lung function was measured at periodic intervals for eight hours after dosing. Safety measurements were also monitored.

Levalbuterol, at doses offering equivalent efficacy to the standard racemic dose, demonstrated an approximate 50 percent reduction in beta-mediated side effects.

"We found we could get significant improvement in the safety profile of the drug," Southwell said. "At the dose that is equivalent to the marketed dose of albuterol, we have a significant increase in efficacy with the R isomer."

Sepracor, of Marlborough, Mass., uses chiral chemistry to develop single-isomer forms of existing pharmaceuticals, primarily for the upper-respiratory, urology and pain markets. Sepracor has one FDA-approved drug, Allegra, an improved form of Seldane for allergy, six drug candidates in clinical development and several in preclinical study. *