Lonhala Magnair (glycopyrrolate; also known as SUN-101/eFlow) is an inhalation solution, developed and marketed by Sunovion Pharmaceuticals, for long-term treatment of chronic obstructive pulmonary disease (COPD).
Lonhala Magnair was approved by the U.S. Food and Drug Administration (FDA) in December 2017, becoming the first nebulized long-acting muscarinic antagonist (LAMA) approved as a maintenance treatment of airflow obstruction in people with COPD.
How Lonhala Magnair works
Acetylcholine is a chemical messenger (or neurotransmitter) responsible for transmitting signals from the nervous system to muscles around the airways in the lungs. To do so, it bind to receptors found on the surface of muscle cells known as muscarinic receptors. When acetylcholine binds to these receptors, the muscles around the airways in the lungs contract and narrow, making it difficult to breathe.
Lonhala Magnair binds to muscarinic receptors and prevents acetylcholine from doing so. This helps muscles around the airways to expand and relax, facilitating the flow of air into the lungs and easing such symptoms as coughing, chest tightness, wheezing, and shortness of breath.
Lonhala Magnair in clinical trials
The safety and effectiveness of Lonhala Magnair in COPD patients were investigated in a series of trials that were part of the GOLDEN clinical program.
The Phase 2b GOLDEN-1 (NCT01426009) crossover trial evaluated the safety and effectiveness of several doses of Lonhala Magnair once daily in 140 patients with moderate-to-severe COPD, treated in seven-day cycles, compared to other treatments or placebo. Results presented at the 2012 European Respiratory Society Annual Congress showed that all doses were well-tolerated, with similar rates of adverse effects compared to placebo, and significant improvements in forced expiratory volume in one second (FEV1), a measure of lung function, against placebo. These results led the investigators to conclude that Lonhala Magnair was safe and provided rapid onset of bronchodilation and sustained improvements in lung function over 24 hours in COPD patients.
The Phase 2 GOLDEN-2 (NCT01706536) and GOLDEN-6 (NCT02038829) studies were to identify an optimal dose of Lonhala Magnair for a Phase 3 study. The two trials — involving a total of 378 patients with moderate-to-severe COPD — assessed increasing doses of Lonhala Magnair (3–100 mcg) twice daily compared to placebo. In GOLDEN-6, a group of patients were also assigned to treatment with Tudorza Pressair (aclidinium bromide), a COPD medication, at 400 mcg twice daily as an open-label active comparator.
Combined GOLDEN-2 and GOLDEN-6 results were published in the journal Respiratory Research, and showed that Lonhala Magnair produced rapid improvements in lung function in five minutes or less after a single-dose, and that those improvements were maintained over a 24-hour period at all doses. Benefits at 25 and 50 mcg doses twice daily of the treated were comparable to Tudorza Pressair at 400 mcg twice daily. Based on this safety and effectiveness data, the 25 and 50 mcg doses of Lonhala Magnair twice daily were chosen for Phase 3 GOLDEN clinical trials.
GOLDEN-3 (NCT02347761) and GOLDEN-4 (NCT02347774) were placebo-controlled Phase 3 trials evaluating Lonhala Magnair in a total of almost 1,300 adults with moderate-to-very-severe COPD. The identical trials tested treatment, given twice daily at either 25 mcg or 50 mcg for 12 weeks against placebo. Results showed significant and clinically meaningful improvements in treated patients FEV1, the study’s primary endpoint, at week 12 compared to study start (baseline), at both dose levels. Both doses of Lonhala Magnair also improved forced vital capacity (FVC), or the amount of air that can be forcibly exhaled after taking the deepest breath possible, and health status as measured by St. George’s Respiratory Questionnaire (SGRQ), a 50-item questionnaire examining quality of life in patients with diseases of airway obstruction. Lonhala Magnair’s safety profile was also acceptable at both doses, and only 5 percent of patients stopping treatment due to adverse reactions.
GOLDEN-5 (NCT02276222) was an open-label and long-term Phase 3 trial evaluating Lonhala Magnair at 50 mcg twice daily against an active comparator, Spiriva (tiotropium bromide) 18 mcg once a day, for 48 weeks at in adults with moderate-to-very-severe COPD. This trial also aimed for a real-world patient population: a wide range of COPD severity, people with comorbiditis (other diseases) and those on background COPD medications. It’s primary goal, or endpoint, were measurements of safety and tolerability; secondary endpoints included changes in FEV1 from baseline and cardiovascular events.
Results showed that the adverse effects were consistent with those observed in the 12-week studies, with Lonhala Magnair well-tolerated over 48 weeks. The most common adverse events being COPD worsening and cough, and found at similar rates between the two treatment groups. But more patients on Lonhala Magnair discontinued treatment over the 48 weeks due to these events than those on Spiriva, 10 percent versus 2.8 percent, respectively. Still, the researchers found the treatment improved FEV1 in patients over time and resulted in them reporting better quality of life, and was safe and well-tolerated, including in cardiovascular measures. They recommended it as a maintenance treatment for moderate-to-very-severe COPD.
Combined analyses of data from the GOLDEN-3, GOLDEN-4, and GOLDEN-5 trials were presented at the 2017 American College of Chest Physicians (CHEST) Annual Meeting in Toronto, Canada. Findings showed that Lonhala Magnair improved lung function and was well-tolerated by people with moderate-to-very-severe COPD, including those with cardiovascular risk factors, on background long-acting beta2 agonist (LABA) therapy, and in those more than 65 years of age.
Lonhala Magnair comes as an inhalation solution delivered through the Magnair nebulizer, a portable device that allows for quick delivery of the medication to the lungs while breathing normally.
It is approved in the U.S. as a long-term, maintenance treatment of airflow obstruction in people with COPD, including those with chronic bronchitis and/or emphysema.
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