MannKind Corporation has received clearance from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) to initiate the Phase 3 ICoN-1 clinical trial of Clofazimine Inhalation Suspension for the treatment of nontuberculous mycobacterial (NTM) lung disease. This clearance allows the global study to proceed in four countries, including the U.S., Japan, South Korea, and Australia, with Taiwan expected to follow in Q4 2024.
The ICoN-1 trial, already underway in the United States since June 2024, is a multi-national, randomized, double-blind, placebo-controlled Phase 3 study. It aims to evaluate the efficacy and safety of Clofazimine Inhalation Suspension when added to guideline-based therapy in adults with refractory NTM lung disease caused by mycobacterium avium complex (MAC), followed by an open-label extension. The co-primary endpoints in the U.S. are sputum culture conversion (negative for NTM) from baseline to end of Month 6 and change in quality of life (QoL) during the same timeframe. Outside the U.S., the primary endpoint is sputum culture conversion.
Growing Global Concern of NTM Lung Disease
NTM lung disease is a rare disease with a rising prevalence worldwide, impacting over 100,000 individuals in the U.S. and over 150,000 in Japan in 2022. It is associated with shortened life span, high morbidity, and significant impact on patients’ quality of life. NTM comprises nearly 200 species, with MAC accounting for approximately 80% of all NTM lung disease cases in the United States. Approximately 15-20% of NTM patients are refractory, meaning they do not respond to standard treatments.
Regulatory Support and Market Exclusivity
In May 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for Clofazimine Inhalation Suspension (MNKD-101) for the treatment of NTM lung disease. The FDA also previously designated Clofazimine Inhalation Suspension as both an orphan drug and a qualified infectious disease product (QIDP) for the treatment of pulmonary NTM infections. A drug that receives orphan drug exclusivity receives seven years of exclusivity, and one that also earns QIDP designation, may receive an additional five years of market exclusivity.
Trial Enrollment and Design
The ICoN-1 study intends to enroll approximately 230 eligible participants at more than 100 sites across the U.S. and globally to ensure a minimum of 180 participants are evaluable for efficacy. The trial is designed to assess the drug's ability to achieve sputum culture conversion and improve the quality of life for patients with NTM lung disease.
Expert Commentary
Dr. Kozo Morimoto, lead principal investigator for ICoN-1 in Japan, stated, “Patients living with NTM infections deserve safe, well-tolerated, convenient, and effective options to treat this serious respiratory disease that is on the rise in Japan, as well as globally.”
