PURPOSE: Acute exacerbations of asthma are an increasingly important and costly burden. This study was designed to assess the safety and efficacy of intravenous MN-221 as add-on to standard of care (SOC) in a Emergency Department (ED) setting.
METHODS: The study was randomized, placebo-controlled, dose-escalation, and multicenter. 29 patients received SOC (nebulized albuterol and ipratropium plus oral corticosteroid). Patients with FEV1 ≤ 55% of predicted were randomized to MN-221 [240 or 450 ug infused over 15 min or 1080 ug over 2 hr] or Placebo. Safety, efficacy and PK parameters were monitored hourly throughout a 5 hr treatment period and a 24 hr follow-up visit. Nebulized albuterol (2.5 mg) and/or ipratropium (0.5 mg) was available hourly during screening and treatment phases. Efficacy endpoints included spirometry, dyspnea indexing, albuterol use, and hospitalization rates.
RESULTS: The study was completed with n=13 in SOC + Placebo and n=16 receiving SOC + MN-221; 5 at 240 ug, 6 at 450 ug, and 5 intended for a 1080 ug dose (2 patients actually received 1995 ug). MN-221 was well-tolerated. MN-221 efficacy included: 1) reduced hospitalization rate: 4/16 (25%) in the all MN-221 group vs 7/13 (54%) in Placebo arm, and 2) improved FEV1 (% predicted): it was elevated in the all MN-221 group (change from baseline in AUC1-5hr was 43% higher in the all MN-221 group vs Placebo). The majority of adverse events were mild to moderate in intensity and SAEs were lower in the all MN-221 group vs Placebo and were asthma AEs. No abnormal ECG findings were observed and heart rate was minimally elevated in the all MN-221 group relative to Placebo.
CONCLUSION: MN-221 adjunctive to standard therapy for severe acute asthma exacerbations was safe and appeared to provide additional clinical benefit. The results support further clinical development of MN-221.
CLINICAL IMPLICATIONS: MN-221 appears to be a unique, safe, and clinically-beneficial adjunctive pharmacotherapy for the treatment of acute asthma. Further development is warranted.
DISCLOSURE: Richard Nowak, Shareholder Iwaki, Matsuda, Johnson and Dunton are shareholders of MediciNova, Inc.; Employee Iwaki, Matsuda, Johnson and Dunton are employees of MediciNova, Inc; Consultant fee, speaker bureau, advisory committee, etc. Dr. Nowak was a principal investigator in the study and was compensated for his efforts. He is also an advisor to MediciNova, Inc.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. MN-221 is a new beta adrenoreceptor agonist under development by MediciNova, Inc.