ATS 2009: New Sustained 24-Hour Bronchodilation Drug for COPD Passes Muster

Kristina Rebelo

May 27, 2009

May 27, 2009 (San Diego, California) — The novel once-daily inhalation β2-agonist indacaterol was well tolerated, had safety profiles similar to placebo (both at 150 μg and 300 μg doses), and provided sustained 24-hour bronchodilation with rapid onset for patients with moderate to severe chronic obstructive pulmonary disease (COPD), according to pivotal phase 3 data released here at ATS 2009: the American Thoracic Society International Conference.

The 26-week trial was a randomized double-blind placebo-controlled study of indacaterol in COPD patients, with open-label tiotropium, which had a primary efficacy variable of trough forced expiratory volume in 1 second (FEV1) after 12 weeks. Secondary efficacy variables included trough FEV1, FEV1, and forced vital capacity at other time points, and peak FEV1. The subjects were 40 years or older with a smoking history of 20-pack-years or more. Of the more than 1200 patients in this group of the 7-group study, 420 received 150 μg, 418 received 300 μg, and 425 received placebo, all through a single-dose dry powder inhaler; safety assessments included adverse events.

"The subjects were randomized and were very carefully characterized and evenly mated as far as the severity of their disease, with an average FEV1 of 56% predicted," lead investigator Charles Fogarty, MD, from Spartanburg Medical Research in South Carolina, told Medscape Pulmonary Medicine in a telephone interview after the presentation.

Patients visited the participating clinics after 2, 4, 8, 12, 16, 21, and 26 weeks. Study treatments were taken each morning between the hours of 8:00 and 10:00. Rescue medication was albuterol/salbutamol. Seventy-seven percent of subjects completed the lengthy trial.

Indacaterol at 150 μg and 300 μg significantly improved lung function at 12 weeks, compared with placebo. Improvements in FEV1 were observed after 1 day (110 mL for 150 μg and 140 mL for 300 μg), at the 12-week primary end point (180 mL for both doses), and at 26 weeks (160 mL for 150 μg and 180 mL for 300 μg). Results were statistically significant (P < .001) for each of the doses, compared with placebo, at each of these time points.

Adverse events were similar in numbers of patients across all treatment groups. There were 42 severe adverse events in the 150 μg group, 31 in the 300 μg group, and 41 in the placebo group. The most frequent adverse events were respiratory tract infections and respiratory disorders; there were 2 deaths, 1 in the 150 μg group and 1 in the placebo group.

Dr. Fogarty said: "I'm in private practice and I see a lot of COPD patients. I'm aware that sometimes they get confused and take an extra dose, so there's some reassurance that if they accidentally take an extra dose, there is very little safety risk. In looking at my patients, if they're on other once-a-day drugs, they may forget to take the second dose of one; with this once-a-day indacaterol, there's the likelihood of better compliance if they take all their drugs just once a day."

"Another advantage of this 24-hour drug is that it is still working and onboard from the day before, at around 180 mL in the morning," said Dr. Fogarty. "Patients are not crashing from running out of their medicine, so there's less grasping for a rescue inhaler first thing."

Dr. Nick Hanania

Nicola Hanania, MD, MS, FRCP(C), FACP, FCCP, director of the Adult Asthma Clinic, Pulmonary Diagnostic Laboratory at Ben Taub General Hospital, and associate professor of medicine at Baylor College of Medicine in Houston, Texas, who was coinvestigator on the 26-week trial, commented on the study after the presentation.

"COPD is a disabling disease associated with significant morbidities," he told Medscape Pulmonary Medicine. "As a pulmonologist, the message I got from these studies is that the drug is efficacious over a 24-hour period, with a sustained effect up to 1 year, as shown in the studies. COPD patients have had limited options to date and we have been looking for novel agents that we can add to the few other drugs we have for these patients. The biggest need is to diagnose COPD early — underdiagnosis is a major problem."

James F. Donohue, MD, professor of medicine and division chief of pulmonary diseases and critical care medicine at the University of North Carolina School of Medicine in Chapel Hill, who chaired another session in which indacaterol research was released, told Medscape Pulmonary Medicine in a telephone interview that he thought the results of the efficacy and safety study were impressive.

"You take the drug and then 23 hours and 55 minutes later, you measure the lung function, and those results were particularly robust," said Dr. Donohue. "And most impressively, . . . the safety data profile was very encouraging."

Dr. Fogarty has received research grants from Novartis as the principal investigator on indacaterol, but has no stock in the company. Dr. Hanania was a 26-week principal investigator on this trial, whose duties included the oversight of recruitment of patients, enrollment, randomization, adverse events, and collection of data. He is on the Novartis Advisory Board for indacaterol and for other COPD drugs. Dr. Donohue has conducted clinical trials and has been on advisory boards for Novartis but has not done lectures for Novartis.

ATS 2009: American Thoracic Society International Conference: Abstract J57. Presented May 19, 2009.

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